Genetics &amp; Molecular Biology https://scienceblogs.com/ en Zika virus, drug discovery, and student projects https://scienceblogs.com/digitalbio/2016/03/09/zika-virus-drug-discovery-and-student-projects <span>Zika virus, drug discovery, and student projects</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><p>It's well understood in science education that students are more engaged when they work on problems that matter.  Right now, Zika virus matters.  Zika is a very scary problem that matters a great deal to anyone who might want to start a family and greatly concerns my students.</p> <p>I teach a bioinformatics course where students use computational tools to research biology.  Since my students are learning how to use tools that can be applied to this problem, I decided to have them apply their new bioinformatics skills to identify drugs that work against Zika virus.</p> <p>We don't have the lab facilities to test drug candidates, but it's nice for students to realize they're learning skills that could be put to use.</p> <p>Here's what we're doing:</p> <ol><li>Looking at background information about Zika virus.</li> <li>Using blastp to identify related proteins that are also bound to drugs.</li> <li>Using molecular modeling to see if those drugs might also bind to Zika virus proteins.</li> </ol><p> </p> <p><strong>Getting up-to-speed on Zika virus</strong></p> <p>We found a great compilation of <a href="http://www.ncbi.nlm.nih.gov/genome/viruses/variation/Zika/" target="_blank">Zika resources at the NCBI</a>.  <a href="http://www.cidrap.umn.edu/infectious-disease-topics/zika#literature" target="_blank">CIDRAP has a great set of Zika resources</a> as well.</p> <p>My students go to the NCBI Zika resource, select the link to publications, and scan the titles to see what's new.  This list is a bit overwhelming, so I ask them to focus on the first and last sentences in the abstract from P. Brasil et. al., <a href="http://www.ncbi.nlm.nih.gov/pubmed/26943629" target="_blank">Zika Virus Infection in Pregnant Women in Rio de Janeiro</a>, and on <a href="http://www.sciencedirect.com/science/article/pii/S1934590916001065" target="_blank">this publication from Tang, et. al</a>.  They need to identify birth defects associated with Zika virus infection and summarize two kinds of data that support the association between infection and birth defects.</p> <p>Next, they use the <a href="http://www.healthmap.org/zika/#timeline" target="_blank">Health Map</a> link to see where infections are occurring.  It gets more personal when you see cases happening in your state.</p> <div style="width: 410px;float:left;"><img class="size-large wp-image-1214" src="http://scienceblogs.com/digitalbio/files/2016/03/Healthmap-400x239.png" alt="Health Map shows Zika virus cases in real time." width="400" height="239" /><a href="http://www.healthmap.org/zika/#timeline" target="_blank">Health Map </a>shows Zika virus cases in real time. </div> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p>We also look at the <a href="http://viralzone.expasy.org/all_by_species/6756.html" target="_blank">ViralZone page from Expasy</a> to learn about the Zika life cycle and see how the Zika polyprotein gets chopped into smaller parts.  This has a link to an interesting Wikipedia page for a Zika virus receptor (<a href="https://en.wikipedia.org/wiki/DC-SIGN" target="_blank">DC-SIGN or CD209</a>) that appears to be expressed in the uterus and on brain cells–at least that's my interpretation of the RNA expression data.</p> <p>But, it's easy to get lost clicking too many links, so we go on to protein blast.</p> <p> </p> <p><strong>Identifying potential drug targets with BLAST</strong></p> <p>I think the easiest way to find a drug against a virus is to start by looking at compounds we already know about.  We know that many successful antiviral drugs target viral proteases and polymerases, so my students go to the Zika virus reference genome (thanks NCBI!) and get the protein sequences for the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Search&amp;db=protein&amp;term=YP_009227202.1&amp;dopt=GenBank" target="_blank">Zika virus protease NS3</a> and the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Search&amp;db=protein&amp;term=YP_009227205.1&amp;dopt=GenBank" target="_blank">Zika virus RNA dependent RNA polymerase</a>.</p> <p>Then they use protein blast to search the NCBI structure database and see if there are 3D structures from related viruses that are bound to drugs.</p> <p>Once they've found a structure to work with, they reverse the search and use blastp to compare their new sequence to the sequence of the Zika protein.</p> <p> </p> <p><strong>Using molecular models to see if drugs might bind to Zika virus</strong></p> <p>Once our students have found structures that contain a drug, they look at amino acids that are near the drug to see if those residues are similar to those in Zika virus.</p> <p> </p> <p><strong>Would Sovaldi® (Sofosbuvir) work against Zika virus?</strong></p> <p>Whenever possible, I like to give examples to show an investigation might work.  When I noticed that some of my blast results included proteins from Hepatitis C virus, I decided to use this as an example.  There's a drug that works by inhibiting the RNA polymerase in Hepatitis C  (<a href="http://www.sovaldi.com" target="_blank">Sovaldi® from Gilead</a>), so I decided to find out if it might work against Zika as well.</p> <div style="width: 410px;float:left;"><img class="size-large wp-image-1216" src="http://scienceblogs.com/digitalbio/files/2016/03/IMG_2927-400x283.png" alt="Hepatitis C virus RNA polymerase bound to Sovadi® (Sofosbuvir) from 4WTG colored by charge." width="400" height="283" /> Hepatitis C virus RNA polymerase bound to Sovadi® (Sofosbuvir) from 4WTG colored by charge. </div> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p>First, I did a blastp search and compared the protein sequence from the structure 4WTG against Zika virus RNA polymerase.</p> <div style="width: 410px;float:left;"><img class="size-large wp-image-1215" src="http://scienceblogs.com/digitalbio/files/2016/03/HepC_vZika-400x101.png" alt="blastp results from comparing Zika virus RNA polymerase to the Hepatitis C virus polymerase in 4WTG" width="400" height="101" /> blastp results from comparing Zika virus RNA polymerase to the Hepatitis C virus polymerase in 4WTG. </div> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p>Only 25% of the amino acids are identical, but the E value is 0.007, so that's encouraging.   I decided to take a closer look.</p> <p>I used 4WTG as a query sequence in blastp to align it to the Zika virus polymerase sequence.  Then, I downloaded the 4WTG structure and opened it in Molecule World. I selected the drug and used the Select Nearby feature to identify amino acids that might be bound to the drug. Returning to the aligned sequences, I highlighted those amino acids in the alignment.</p> <p><img class="alignleft size-large wp-image-1213" src="http://scienceblogs.com/digitalbio/files/2016/03/Blastp_HepC_Zika-400x85.png" alt="Blastp_HepC_Zika" width="400" height="85" /></p> <p> </p> <p> </p> <p> </p> <p>Interestingly, the drug binds to amino acids that are present in the same positions in both Zika virus RNA polymerase and in the Hepatitis C virus RNA polymerase.  Cool!</p> <p>I took a closer look.  In the top image, two manganese atoms bound to the drug are also bound to aspartic acid residues.  These are present in both proteins.</p> <div style="width: 410px;float:left;"><img class="size-large wp-image-1211" src="http://scienceblogs.com/digitalbio/files/2016/03/IMG_2924-400x283.png" alt="Amino acids that interact with Sovaldi® are colored by residue in Molecule World and drawn as tubes." width="400" height="283" /> Amino acids that interact with Sovaldi® are colored by residue in Molecule World and drawn as tubes. </div> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p>In the bottom image, I can see an arginine that's present in both proteins.  Here, it appears to participate in an ionic interaction with the drug.</p> <div style="width: 410px;float:left;"><img class="size-large wp-image-1212" src="http://scienceblogs.com/digitalbio/files/2016/03/IMG_2925-400x283.png" alt="Amino acids that interact with Sovaldi® are drawn with in a space filling mode and colored by element in Molecule World." width="400" height="283" /> Amino acids that interact with Sovaldi® are drawn with in a space filling mode and colored by element in Molecule World. </div> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p>Now, these models don't prove that Sovaldi would inhibit Zika virus replication.  But it might be worth taking a look.  If I were culturing brain stem cells like Tang, et. al (3), I might take out a loan to buy some Sovaldi® and add it to the growth medium.   Just to see what happens.</p> <p>For now, I'm looking forward to seeing what my students find.</p> <p>Note:  All the molecular modeling work described here was carried out with the <a href="https://geo.itunes.apple.com/us/app/molecule-world/id863565223?mt=8&amp;at=10lGBR&amp;ct=zika" target="_blank">Molecule World iPad app</a> from Digital World Biology.</p> <p> </p> <p><strong>References</strong>:</p> <ol><li> <a href="http://www.ncbi.nlm.nih.gov/genome/viruses/variation/Zika/">The Zika Virus Resource at the National Center for Biotechnology Information</a></li> <li> <p class="desc">Brasil P, et.al.  <a href="http://www.ncbi.nlm.nih.gov/pubmed/26943629" target="_blank">Zika Virus Infection in Pregnant Women in Rio de Janeiro</a> <span class="jrnl" title="The New England journal of medicine">N Engl J Med</span>. 2016 Mar 4. [Epub ahead of print]</p> </li> <li>Tang et al., Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth, Cell Stem Cell (2016),  <a href="http://dx.doi.org/10.1016/j.stem.2016.02.016">http://dx.doi.org/10.1016/j.stem.2016.02.016</a></li> <li>Stephen F. Altschul, Thomas L. Madden, Alejandro A. Schäffer, Jinghui Zhang, Zheng Zhang, Webb Miller, and David J. Lipman (1997), "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs", Nucleic Acids Res. 25:3389-3402.</li> <li>Appleby TC, Perry JK, Murakami E, Barauskas O, Feng J, Cho A, Fox D 3rd,<br /> Wetmore DR, McGrath ME, Ray AS, Sofia MJ, Swaminathan S, Edwards TE. <a href="http://www.ncbi.nlm.nih.gov/pubmed/25678663">Viral</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/25678663"> replication. Structural basis for RNA replication by the hepatitis C virus</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/25678663"> polymerase</a>. Science. 2015 Feb 13;347(6223):771-5. doi: 10.1126/science.1259210.</li> </ol><p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> </div> <span><a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a></span> <span>Tue, 03/08/2016 - 18:10</span> <div class="field field--name-field-blog-tags field--type-entity-reference field--label-inline"> <div class="field--label">Tags</div> <div class="field--items"> <div class="field--item"><a href="/tag/biotechnology" hreflang="en">biotechnology</a></div> <div class="field--item"><a href="/tag/blast" hreflang="en">BLAST</a></div> <div class="field--item"><a href="/tag/genetics-molecular-biology" hreflang="en">Genetics &amp; Molecular Biology</a></div> <div class="field--item"><a href="/tag/ipad-apps" hreflang="en">iPad apps</a></div> <div class="field--item"><a href="/tag/molecular-modeling" hreflang="en">molecular modeling</a></div> <div class="field--item"><a href="/tag/molecule-world" hreflang="en">Molecule World</a></div> <div class="field--item"><a href="/tag/viruses" hreflang="en">viruses</a></div> </div> </div> <section> <article data-comment-user-id="0" id="comment-1903432" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1457785376"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>Sandra, that is fantastic, and you are doing great work. Your ideas need to go viral, so faculty in other universities can start doing likewise, pursuing this in whatever ways they can.</p> <p>This can also be done for many of the other pressing issues of our time. Undergraduate education should include whatever work on real problems and real solutions is possible within the scope of the subject matter, in every field. If the kids are going to be learning basic principles whether they take that approach or the more conventional approach, there's no reason not to do it.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903432&amp;1=default&amp;2=en&amp;3=" token="L6-pmW1m5G1-0sAXcz6M_exp4lZ15cVkvdDjDCA3a2I"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">G (not verified)</span> on 12 Mar 2016 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903432">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="105" id="comment-1903433" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1457882902"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>Thanks! I'm a firm believer in learning by doing but I'm not the only one. </p> <p>The Vision and Change report and follow on articles by the National Science Foundation show there are many instructors that share the desire to have students use what they're learning and study problems they care about.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903433&amp;1=default&amp;2=en&amp;3=" token="UrvG6T-823IUgBvJXUPmE8E3iS9CHdUfG679rO6uwLY"></drupal-render-placeholder> </div> <footer> <em>By <a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a> on 13 Mar 2016 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903433">#permalink</a></em> <article typeof="schema:Person" about="/author/sporte"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/author/sporte" hreflang="en"><img src="/files/styles/thumbnail/public/pictures/59121-arsenic_protein-150x150-120x120.png?itok=o0ajJdDI" width="100" height="100" alt="Profile picture for user sporte" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> </section> <ul class="links inline list-inline"><li class="comment-forbidden"><a href="/user/login?destination=/digitalbio/2016/03/09/zika-virus-drug-discovery-and-student-projects%23comment-form">Log in</a> to post comments</li></ul> Tue, 08 Mar 2016 23:10:56 +0000 sporte 69982 at https://scienceblogs.com Protein modeling and the Siamese cat https://scienceblogs.com/digitalbio/2015/12/31/protein-modeling-and-the-siamese-cat <span>Protein modeling and the Siamese cat</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><p>"<em>By night all cats are gray</em>"  - Miguel Cervantes in Don Quixote</p> <p> </p> <p>I've always liked Siamese cats.   Students do, too.  "Why Siamese cats wear masks" is always a favorite story in genetics class.  So, when I opened my January copy of <a href="http://www.nsta.org/highschool/" target="_blank">The Science Teacher</a>, I was thrilled to see an article on Siamese cat colors and proteins AND molecular genetics (1).</p> <p>In the article, the authors (Todd and Kenyon) provide some background information on the enzymatic activity of tyrosinase and compare it to the catechol oxidase that causes fruit to brown, especially apples.  Tyrosinase catalyzes the first step of a biochemical pathway where tyrosine is converted to dopaquinone and then to the dark colored substance, melanin.  Melanin is responsible for the brown color in the ears, paws, tail, and face of Siamese cats.</p> <div style="width: 410px;float:left;"><a href="/files/digitalbio/files/2016/01/melanin.png"><img class="size-large wp-image-1195" src="http://scienceblogs.com/digitalbio/files/2016/01/melanin-400x320.png" alt="Melanin in Molecule World" width="400" height="320" /></a> Melanin in Molecule World </div> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p>The fun part of the story is that some versions of the tyrosinase gene have a mutation that makes this enzyme less stable at warmer temperatures.  In warmer areas of the cat's body, less melanin is produced, giving the cat a lighter colored body.</p> <p>I love the story of the coat coloring  and I think this activity has the potential to interest students.</p> <p>I also like the approach that the authors take with discussing proteins and the associated phenotypes first before getting into DNA and the central dogma.  I use this same order in my bioinformatics class.</p> <p>There are, however, a few things that I would change with this activity.</p> <p><strong>Too many hydroxyl groups</strong></p> <p>First, the article and the teacher guide have the structure of tyrosine wrong.  Tyrosine only has one hydroxyl group attached to the six-carbon ring, as shown below, not two hydroxyl groups as shown in the article and the teachers' guide.</p> <div style="width: 410px;float:left;"><a href="/files/digitalbio/files/2016/01/extra-tyrosine.png"><img class="size-large wp-image-1196" src="http://scienceblogs.com/digitalbio/files/2016/01/extra-tyrosine-400x155.png" alt="Tyrosinase reaction from Teachers' Guide. The extra hydroxyl group is marked." width="400" height="155" /></a> Tyrosinase reaction from Teachers' Guide. The extra hydroxyl group is marked. </div> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p>Space-filling models of Tyrosine and Dopaquinone downloaded from the NCBI's PubChem database are shown below.</p> <div style="width: 410px;float:left;"><a href="/files/digitalbio/files/2015/12/tyrosine_dopaquinone.png"><img class="size-large wp-image-1191" src="http://scienceblogs.com/digitalbio/files/2015/12/tyrosine_dopaquinone-400x186.png" alt="Tyrosine and dopaquinone" width="400" height="186" /></a> Tyrosine and dopaquinone </div> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p><strong>Too many proteins in too short a time</strong></p> <p>Second, I think the authors include way too many different protein stories and different explanations for why a protein might be inactivated.  Todd and Kenyon have done quite a bit of work creating activities with several different proteins. But I think the plan to have students cover all eight proteins in six days would be too confusing for many students.  The activity has students read about or work with:  lactase, cellulase, tyrosinase, catechol oxidase, proteases, kinesin, galactosyl transferase, and tyrosine kinase, not to mention Gleevec and the way it interacts with the BCR-ABL fusion protein.  I teach a college bioinformatics course and even the best of my students would get confused by looking at eight different proteins without some kind of common thread.  The take home lesson that denaturation negatively impacts tyrosinase activity is easy to lose among all the unrelated activities.</p> <p><strong>Where are the 3D models?</strong></p> <p>When I read the description of the article, I thought it might include activities where students looked at 3D protein models to see how they changed when they were denatured by heat or pH. Instead, they just watch a short video. A better approach, I think, would be to have students work first-hand with structure models and see the change for themselves.  Or maybe fry and egg.  The effects of protein denaturation are pretty clear when you watch an egg cook.</p> <p>This is my bias, but I think an active learning approach, where students actually look at 3D protein and chemical models and identify chemical interactions, would be better in long run and better equip students for future learning. I think the common practice of hiding the biochemistry makes genetics much harder to understand and far less straightforward than it should be.</p> <p>And, as it turns out there are 3D models of tyrosinase that students could use.  They're from <em>Bacillus megatherium</em>, but that's how biology works.  If an enzyme activity is beneficial, evolutionary processes tend to keep it around.</p> <p><strong>Using 3D Models to look at albino cats</strong></p> <p>No models exist from the Siamese cat protein with the brown ear point mutation, but it is possible to make 3D protein models that show the affect of a different mutation, in tyrosinase, that leads to albino cats. This mutation occurs when a cytosine is deleted at nucleotide 975, creating a frameshift (2).  To simulate the mutation's effect, we can hide the amino acids that would be lost.  This model isn't perfect because the shorter protein might fold somewhat differently, but this does provide a satisfying explanation for an inactive enzyme.</p> <p>Here's what to do:</p> <ol><li>Open <a href="https://geo.itunes.apple.com/us/app/molecule-world/id863565223?mt=8&amp;at=10lGBR&amp;ct=cat" target="_blank">Molecule World on the iPad</a> (*).</li> <li>Download <a href="http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdb_strview.cgi/mmdb.cn3?program=cn3d&amp;display=0&amp;complexity=3&amp;buidx=1&amp;uid=121933" target="_blank">4P6R</a>.</li> <li>Color the protein chains by molecule.</li> <li>Open the sequence viewer and touch the name of the last row to select it.  This row contains tyrosine, the substrate for the enzyme, and for each chain, two atoms of zinc.</li> <li>Change the coloring style to element.</li> </ol><p>Now, you can see the substrate bound in the active site.  Notice this protein has two identical subunits.  Each one is bound to tyrosine and zinc.</p> <div style="width: 410px;float:left;"><a href="/files/digitalbio/files/2015/12/tyrosinase_normal.png"><img class="size-large wp-image-1192" src="http://scienceblogs.com/digitalbio/files/2015/12/tyrosinase_normal-400x303.png" alt="Tyrosinase with tyrosine and zinc in the active site." width="400" height="303" /></a> Tyrosinase with tyrosine and zinc in the active site. </div> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p>You may want to change the atom visibility to show all the atoms or just the core backbone, like I have here, to see how the tyrosine is positioned.</p> <p>*Many of the things I describe here can be done in Cn3D, but it's a bit more complicated.</p> <p> </p> <p><strong>Modeling the mutation's affect</strong></p> <p>This next part is a little more complicated because I had to split the protein sequence into three parts to avoid introducing spaces.</p> <ol><ol><li>Carry out the following process in three steps. First, copy the sequence below.KYRVRKNVLHLTDTEKRDFVRTVLIKEKGIYDRYIAWHGAAGKFHTPPGSDRNA</li> </ol></ol><p> </p> <ol><ol><li>Touch the Selection button and paste the sequence below in the Select pattern window.</li> <li>Start the search.  The pasted sequence will be highlighted in the protein sequence.</li> <li>Copy the next part of the sequence (below).  Touch the Selection button again and search for this pattern as before.<br /> AHMSSAFLPWHREYLLRFERDQSINPEVTLPYWEWETDAQMQDPSQSQIWSADFMGGN</li> </ol></ol><p> </p> <ol><ol><li>Copy the next part of the sequence (below).  Touch the Selection button again and search for this pattern as before.<br /> GNPIKDFIVDTGPFAAGRWTTIDEQGNPSGGLKRNFGATKAPTLPTRDDVL</li> </ol></ol><p> </p> <ol><li>When you're done highlighting sequences, you'll see each subunit has a region that appears brighter and a region in the center that appears more dim. The bright colored residues are incorporated into the protein before ribosomes encounter the frame shift mutation and a stop codon shortly afterwards. This portion of the protein can be produced in the albino cat.</li> <li>Look at the dim areas of each subunit.  These amino acids would be lost when the frameshift mutation is present.  Notice where the tyrosine is located.</li> </ol><div style="width: 410px;float:left;"><a href="/files/digitalbio/files/2015/12/tyrosinase_affected.png"><img class="size-large wp-image-1193" src="http://scienceblogs.com/digitalbio/files/2015/12/tyrosinase_affected-400x326.png" alt="Residues that would be lost because of the frameshift mutant are shown in gray." width="400" height="326" /></a> Residues that would be lost because of the frameshift mutant are shown in gray. </div> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p>8.  To make the mutations affect on the protein even more clear, open the Show/Hide button and choose "Hide unselected."  The amino acid residues that would be lost because of the mutation disappear.</p> <div style="width: 410px;float:left;"><a href="/files/digitalbio/files/2015/12/tyrosinase_missing.png"><img class="size-large wp-image-1194" src="http://scienceblogs.com/digitalbio/files/2015/12/tyrosinase_missing-400x285.png" alt="Residues that would be lost because of the frame shift mutation are hidden." width="400" height="285" /></a> Residues that would be lost because of the frame shift mutation are hidden. </div> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p>Now, it's really clear.  If the residues that bind tyrosine and modify it's structure are gone, the enzyme is unable to function.  If we don't have tyrosinase working to help make melanin, we get white cats.</p> <p> </p> <p><strong>References</strong>:</p> <ol><li>Amber Todd and Lisa Kenyon, How do Siamese cats get their color? The Science Teacher. 2016;83(1):29-36</li> <li>Imes D, Geary L, Grahn R, Lyons L. Albinism in the domestic cat (<i>Felis catus</i>) is associated with a <i>tyrosinase</i> (<i>TYR</i>) mutation. <i>Animal Genetics</i>. 2006;37(2):175-178. doi:10.1111/j.1365-2052.2005.01409.x.</li> </ol></div> <span><a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a></span> <span>Thu, 12/31/2015 - 01:00</span> <div class="field field--name-field-blog-tags field--type-entity-reference field--label-inline"> <div class="field--label">Tags</div> <div class="field--items"> <div class="field--item"><a href="/tag/classroom-activities" hreflang="en">classroom activities</a></div> <div class="field--item"><a href="/tag/genetics-molecular-biology" hreflang="en">Genetics &amp; Molecular Biology</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> <div class="field--item"><a href="/tag/molecular-modeling" hreflang="en">molecular modeling</a></div> <div class="field--item"><a href="/tag/molecular-structures" hreflang="en">molecular structures</a></div> <div class="field--item"><a href="/tag/molecule-world" hreflang="en">Molecule World</a></div> <div class="field--item"><a href="/tag/science-education" hreflang="en">Science Education</a></div> <div class="field--item"><a href="/tag/structural-biology" hreflang="en">structural biology</a></div> </div> </div> <section> </section> <ul class="links inline list-inline"><li class="comment-forbidden"><a href="/user/login?destination=/digitalbio/2015/12/31/protein-modeling-and-the-siamese-cat%23comment-form">Log in</a> to post comments</li></ul> Thu, 31 Dec 2015 06:00:03 +0000 sporte 69979 at https://scienceblogs.com Making the most of Molecule of the Month with Molecule World https://scienceblogs.com/digitalbio/2015/09/08/making-the-most-of-molecule-of-the-month-with-molecule-world <span>Making the most of Molecule of the Month with Molecule World</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><p>We've been fans of the Molecule of the Month series by David Goodsell, for many years. Not only is Dr. Goodsell a talented artist but he writes very clear descriptions of the ways molecules like proteins, RNA, and DNA work together and function inside a cell.</p> <p>To learn about proteins and their activities, I like to go directly to the <a href="http://www.rcsb.org/pdb/101/motm_archive.do">Molecule of the Month</a> page, where I can find a list of articles organized by molecule type and name.  Many of these articles can also be downloaded in a PDF format.</p> <p>A really nice of his articles is that he includes PDB IDs for all the structures he discusses.  The PDB IDs make it easy to download and interact with the structures in Molecule World.</p> <p>Structures from the articles can be viewed on-line in Jmol, but we prefer a more interactive method where we can download the structures, view the sequences, and use the sequences to show / hide or modify parts of the structure in Molecule World.</p> <p>For example, say we want to know more about the genetic engineering tools Cascade and CRISPR.  These are pretty exciting because they allow scientists to engineer genomes with greater precision than ever before.  To learn more, we select the link to <a href="http://www.rcsb.org/pdb/101/motm.do?momID=181">Cascade and CRISPR</a> from the article list.</p> <p>The articles is great for understanding some of the back story.  To find the structures, we can search the web page with the term "PDB".  Every time the words "PDB entries" or "PDB entry" appear, they'll be followed by a PDB ID.  We can use those PDB IDs to get the structures from the NCBI or PDB databases.</p> <p>At the PDB site, those IDs <em>are</em> linked to database records where we can download the pdb files, but it's not always so easy to figure out which of the ten files is the one you should download.</p> <p>A simpler method, is to type the ID in Molecule World and touch the search button.  When the file name appears, touch the name of the file and the molecule file will be downloaded and opened.</p> <p><a href="/files/digitalbio/files/2015/09/adding-new-structures.png"><img class=" size-large wp-image-1150 aligncenter" src="http://scienceblogs.com/digitalbio/files/2015/09/adding-new-structures-400x368.png" alt="adding new structures" width="400" height="368" /></a></p> <p> </p> <p> </p> <p>For Cascade and CRISPR, the PDB IDs and structures in the article are listed below.  If you're using Molecule World on the iPhone or iPad, I set the links up so that touching the links will download the file and make it easy to open these in the app.</p> <p>All the images below were made in Molecule World.</p> <p>Two views of the cascade surveillance complex, a large complex of proteins and RNA  <a href="http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdb_strview.cgi/mmdb.cn3?program=cn3d&amp;display=0&amp;complexity=3&amp;buidx=1&amp;uid=122417">4TVX</a>, <a href="http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdb_strview.cgi/mmdb.cn3?program=cn3d&amp;display=0&amp;complexity=3&amp;buidx=1&amp;uid=122778">4U7U</a>,</p> <p><a href="/files/digitalbio/files/2015/09/4TVX.png"><img class=" size-large wp-image-1151 aligncenter" src="http://scienceblogs.com/digitalbio/files/2015/09/4TVX-400x509.png" alt="4TVX" width="400" height="509" /></a></p> <p><a href="/files/digitalbio/files/2015/09/4U7U.png"><img class=" size-large wp-image-1152 aligncenter" src="http://scienceblogs.com/digitalbio/files/2015/09/4U7U-400x488.png" alt="4U7U" width="400" height="488" /></a></p> <p>Cas1 and Cas2, proteins that chop up and store viral DNA <a href="http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdb_strview.cgi/mmdb.cn3?program=cn3d&amp;display=0&amp;complexity=3&amp;buidx=1&amp;uid=119621">4P6I</a>,</p> <p><a href="/files/digitalbio/files/2015/09/4P6I.png"><img class=" size-large wp-image-1153 aligncenter" src="http://scienceblogs.com/digitalbio/files/2015/09/4P6I-400x242.png" alt="4P6I" width="400" height="242" /></a></p> <p>Cas3, a nuclease that attacks viral DNA:  <a href="http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdb_strview.cgi/mmdb.cn3?program=cn3d&amp;display=0&amp;complexity=3&amp;buidx=1&amp;uid=122750">4QQW</a>,</p> <p><a href="/files/digitalbio/files/2015/09/4QQW1.png"><img class=" size-large wp-image-1155 aligncenter" src="http://scienceblogs.com/digitalbio/files/2015/09/4QQW1-400x534.png" alt="4QQW" width="400" height="534" /></a></p> <p> </p> <p>Cas9, a CRISPR system from another type of bacteria (<em>Streptococcus pyogenes</em>), with CRISPR RNA bound to target DNA <a href="http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdb_strview.cgi/mmdb.cn3?program=cn3d&amp;display=0&amp;complexity=3&amp;buidx=1&amp;uid=121809">4UN3</a></p> <p><a href="/files/digitalbio/files/2015/09/4UN3.png"><img class=" size-large wp-image-1156 aligncenter" src="http://scienceblogs.com/digitalbio/files/2015/09/4UN3-400x443.png" alt="4UN3" width="400" height="443" /></a></p> <p>And more complexes with both the CRISPR RNA and viral target DNA:  <a href="http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdb_strview.cgi/mmdb.cn3?program=cn3d&amp;display=0&amp;complexity=3&amp;buidx=1&amp;uid=117887">4OO8</a>,</p> <p><a href="/files/digitalbio/files/2015/09/4OO8.png"><img class=" size-large wp-image-1157 aligncenter" src="http://scienceblogs.com/digitalbio/files/2015/09/4OO8-400x416.png" alt="4OO8" width="400" height="416" /></a></p> <p>And our favorite,<a href="http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdb_strview.cgi/mmdb.cn3?program=cn3d&amp;display=0&amp;complexity=3&amp;buidx=1&amp;uid=122928">4QYZ</a>.</p> <p><a href="/files/digitalbio/files/2015/09/4QYZ.png"><img class=" size-large wp-image-1158 aligncenter" src="http://scienceblogs.com/digitalbio/files/2015/09/4QYZ-400x413.png" alt="4QYZ" width="400" height="413" /></a></p> <p>My favorite way to view some of these is to open the sequence viewer, find and select the nucleic sequences, and color by residue to distinguish between the RNA and DNA.  We made the RNA residues a little brighter since they're more chemically active.  It also helps to draw the models in different ways to see how the RNA is positioned inside the protein complex.</p> <p>To learn more about CRISPR and the Cascade proteins, iBiology has a <a href="https://vimeo.com/124545344">great video interview with Jennifer Doudna</a>, the woman who discovered this system.</p> </div> <span><a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a></span> <span>Tue, 09/08/2015 - 16:52</span> <div class="field field--name-field-blog-tags field--type-entity-reference field--label-inline"> <div class="field--label">Tags</div> <div class="field--items"> <div class="field--item"><a href="/tag/biotechnology" hreflang="en">biotechnology</a></div> <div class="field--item"><a href="/tag/classroom-activities" hreflang="en">classroom activities</a></div> <div class="field--item"><a href="/tag/genetics-molecular-biology" hreflang="en">Genetics &amp; Molecular Biology</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> <div class="field--item"><a href="/tag/teaching" hreflang="en">teaching</a></div> <div class="field--item"><a href="/tag/web-resources" hreflang="en">web resources</a></div> <div class="field--item"><a href="/tag/crispr" hreflang="en">CRISPR</a></div> <div class="field--item"><a href="/tag/molecule-world" hreflang="en">Molecule World</a></div> <div class="field--item"><a href="/tag/molecules" hreflang="en">molecules</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> </div> </div> <section> </section> <ul class="links inline list-inline"><li class="comment-forbidden"><a href="/user/login?destination=/digitalbio/2015/09/08/making-the-most-of-molecule-of-the-month-with-molecule-world%23comment-form">Log in</a> to post comments</li></ul> Tue, 08 Sep 2015 20:52:00 +0000 sporte 69975 at https://scienceblogs.com Development and Role of the Human Reference Sequence in Personal Genomics https://scienceblogs.com/digitalbio/2014/07/03/development-and-role-of-the-human-reference-sequence-in-personal-genomics <span>Development and Role of the Human Reference Sequence in Personal Genomics</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><p style="color: #000000">A few weeks back, we <a href="http://onlinelibrary.wiley.com/doi/10.1002/9780470015902.a0025334/abstract">published a review</a> about the development and role of the human reference genome. A key point of the reference genome is that it is not a single sequence. Instead it is an assembly of consensus sequences that are designed to deal with variation in the human population and uncertainty in the data. The reference is a map and like a geographical maps evolves though increased understanding over time.</p> <p style="color: #000000">From the Wiley On Line site:</p> <h3 style="color: #000000">Abstract</h3> <div class="subsection" style="color: #000000"> <div class="para"> <p>Genome maps, like geographical maps, need to be interpreted carefully. Although maps are essential to exploration and navigation they cannot be completely accurate. Humans have been mapping the world for several millennia, but genomes have been mapped and explored for just a single century with the greatest advancements in making a sequence reference map of the human genome possible in the past 30 years. After the <span class="bioNameInfoAsset bioName">deoxyribonucleic acid (DNA)</span> sequence of the human genome was completed in 2003, the reference sequence underwent several improvements and today provides the underlying comparative resource for a multitude genetic assays and biochemical measurements. However, the ability to simplify genetic analysis through a single comprehensive map remains an elusive goal.</p> </div> </div> <div class="subsection" style="color: #000000"> <h4 id="a0025334-sec-0002" class="section2">Key Concepts:</h4> <div class="para"> <ul id="a0025334-lst1-0001" class="bullet"><li> <div class="para"> <p>Maps are incomplete and contain errors.</p> </div> </li> <li> <div class="para"> <p>DNA sequence data are interpreted through biochemical experiments or comparisons to other DNA sequences.</p> </div> </li> <li> <div class="para"> <p>A reference genome sequence is a map that provides the essential coordinate system for annotating the functional regions of the genome and comparing differences between individuals' genomes.</p> </div> </li> <li> <div class="para"> <p>The reference genome sequence is always product of understanding at a set point in time and continues to evolve.</p> </div> </li> <li> <div class="para"> <p>DNA sequences evolve through duplication and mutation and, as a result, contain many repeated sequences of different sizes, which complicates data analysis.</p> </div> </li> <li> <div class="para"> <p>DNA sequence variation happens on large and small scales with respect to the lengths of the DNA differences to include single base changes, insertions, deletions, duplications and rearrangements.</p> </div> </li> <li> <div class="para"> <p>DNA sequences within the human population undergo continual change and vary highly between individuals.</p> </div> </li> <li> <div class="para"> <p>The current reference genome sequence is a collection of sequences, an assembly, that include sequences assembled into chromosomes, sequences that are part of structurally complex regions that cannot be assembled, patches (fixes) that cannot be included in the primary sequence, and high variability sequences that are organised into alternate loci.</p> </div> </li> <li> <div class="para"> <p>Genetic analysis is error prone and the data require validation because the methods for collecting DNA sequences create artifacts and the reference sequence used for comparative analyses is incomplete.</p> </div> </li> </ul></div> </div> <div class="keywords" style="color: #000000"></div> </div> <span><a title="View user profile." href="/author/finchtalk" lang="" about="/author/finchtalk" typeof="schema:Person" property="schema:name" datatype="">finchtalk</a></span> <span>Thu, 07/03/2014 - 12:14</span> <div class="field field--name-field-blog-tags field--type-entity-reference field--label-inline"> <div class="field--label">Tags</div> <div class="field--items"> <div class="field--item"><a href="/tag/bioinformatics" hreflang="en">bioinformatics</a></div> <div class="field--item"><a href="/tag/genetics-molecular-biology" hreflang="en">Genetics &amp; Molecular Biology</a></div> <div class="field--item"><a href="/tag/genome" hreflang="en">Genome</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> <div class="field--item"><a href="/tag/sequence-analysis" hreflang="en">sequence analysis</a></div> <div class="field--item"><a href="/tag/dna-sequencing" hreflang="en">DNA sequencing</a></div> <div class="field--item"><a href="/tag/bioinformatics" hreflang="en">bioinformatics</a></div> <div class="field--item"><a href="/tag/genome" hreflang="en">Genome</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> </div> </div> <section> </section> <ul class="links inline list-inline"><li class="comment-forbidden"><a href="/user/login?destination=/digitalbio/2014/07/03/development-and-role-of-the-human-reference-sequence-in-personal-genomics%23comment-form">Log in</a> to post comments</li></ul> Thu, 03 Jul 2014 16:14:43 +0000 finchtalk 69961 at https://scienceblogs.com How do nucleosomes keep our DNA from reaching the sun? https://scienceblogs.com/digitalbio/2014/05/27/nucleosomes-keep-dna-from-reaching-sun <span>How do nucleosomes keep our DNA from reaching the sun?</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><p>A key concept in science is molecular scale. DNA is a fascinating molecule in this regard.</p> <p>While we cannot "see" DNA molecules without the aid of advanced technology, a full length DNA molecule can be very long. In human cells, other than sperm and eggs, six billion base pairs of DNA are packaged into 22 pairs of chromosomes, plus two sex chromosomes. Each base pair is 34 angstroms in length (.34 nanometers, or ~0.3 billionths of a meter), so six billion base pairs (all chromosomes laid out head to toe) form a chain that's two-meters long. If we could hang this DNA chain from a hook, it would be slightly taller than an average human [2]. But that's just the DNA from one cell. Each of us have around 50 trillion cells (50,000 billion).  If we took the DNA from all of those cells and laid it out in a linear fashion, it could wrap around the earth 2.5 million times, or reach to the sun and back 300 times [3]! Yet cells manage to pack all that DNA into a structure so small we can't even see it without a microscope. How does this happen?</p> <div style="width: 209px;float:right;"><a href="/files/digitalbio/files/2014/05/IMG_0191.jpg"><img class="wp-image-1013" src="http://scienceblogs.com/digitalbio/files/2014/05/IMG_0191-300x279.jpg" alt="IMG_0191" width="199" height="185" /></a> Nucleosome from [4] in Molecule World using space fill and element coloring </div> <p>Biology solves the packing problem with nucleosomes.</p> <p>In the early 1900's scientists understood that chromosomes contained genes [4]. When stained, these colorful bodies, could be observed under the microscope and scientists determined that chromosomes contained both protein and DNA. As you might know, genes are DNA.  In a chromosome, DNA is packed into a smaller structure by winding it around a set of histone proteins, just like you might pack up a cord by winding it around your hand.  This compact structure is the nucleosome [3].</p> <p>The first publication of a nucleosome structure was in 1997 [5]. Since then, many hundreds of nucleosome structures have been added to public databases like the <a href="http://www.rcsb.org/pdb/home/home.do">PDB</a> (the Protein Data Bank) and <a href="http://www.ncbi.nlm.nih.gov/structure/">MMDB</a> (the Molecular Modeling Database). Nearly 100 of these structures from a variety of organisms (humans, cows, chickens, frogs, and yeast) show how DNA wraps around a core of histone proteins. Some of these structures were solved and published to understand the interactions between the proteins and DNA and  the implications of the higher-order structure.  Other nucleosome structures were solved in order to study the effects of mutations in DNA sequences or histone proteins.  The changes in these structures are interesting to researchers because nucleosomes play an important role in DNA accessibility.  The accessibility or inaccessiblity of DNA to enzymes like RNA polymerase, for example, is important for normal cellular function and, when disrupted, can contribute to diseases like cancer.  Hence, nucleosomes can be good targets for drugs that treat cancer or act by inhibiting transcription.</p> <p>In  <a href="http://digitalworldbiology.com/dwb/products/molecule-world">Molecule World™</a>, you can explore these structures and learn about the chemical properties of the molecules that make up these structures and investigate their interactions.</p> <table align="center"><tbody><tr><td> <div style="width: 270px;"><a href="/files/digitalbio/files/2014/05/IMG_0192.jpg"><img class="wp-image-1016" src="http://scienceblogs.com/digitalbio/files/2014/05/IMG_0192-300x212.jpg" alt="IMG_0192" width="260" height="184" /></a> Structure showing the DNA "supergroove" with a polyamide dimer bound (white) [6]. Space fill with charge highlighted in Molecule World. </div> </td> <td> <div style="width: 270px;"><a href="/files/digitalbio/files/2014/05/IMG_0193.jpg"><img class="wp-image-1017" src="http://scienceblogs.com/digitalbio/files/2014/05/IMG_0193-300x212.jpg" alt="IMG_0193" width="260" height="184" /></a> Structure with molecule highlighting in Molecule World showing the individual strands of DNA and histone proteins in different colors. </div> </td> </tr></tbody></table><p><strong>References</strong></p> <p>1. Next Generation Science Standards: From molecules to Organisms (<a href="http://www.nextgenscience.org/msls1-molecules-organisms-structures-processes">http://www.nextgenscience.org/msls1-molecules-organisms-structures-proc…</a>)</p> <p>2. Average human height: <a href="http://en.wikipedia.org/wiki/Human_height#Average_height_around_the_world">http://en.wikipedia.org/wiki/Human_height#Average_height_around_the_wor…</a></p> <p>3. DNA Packaging: <a href="http://www.nature.com/scitable/topicpage/dna-packaging-nucleosomes-and-chromatin-310">http://www.nature.com/scitable/topicpage/dna-packaging-nucleosomes-and-…</a></p> <p>4. <span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Biological+Bulletin&amp;rft_id=info%3Adoi%2F10.2307%2F1535741&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=The+Chromosomes+in+Heredity&amp;rft.issn=00063185&amp;rft.date=1903&amp;rft.volume=4&amp;rft.issue=5&amp;rft.spage=231&amp;rft.epage=&amp;rft.artnum=http%3A%2F%2Fwww.jstor.org%2Fstable%2F1535741%3Forigin%3Dcrossref&amp;rft.au=Sutton%2C+W.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Biology">Sutton, W. (1903). The Chromosomes in Heredity <span style="font-style: italic;">Biological Bulletin, 4</span> (5) DOI: <a href="http://dx.doi.org/10.2307/1535741" rev="review">10.2307/1535741</a></span></p> <p>5. <span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Nature&amp;rft_id=info%3Apmid%2F9305837&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=Crystal+structure+of+the+nucleosome+core+particle+at+2.8+A+resolution.&amp;rft.issn=0028-0836&amp;rft.date=1997&amp;rft.volume=389&amp;rft.issue=6648&amp;rft.spage=251&amp;rft.epage=60&amp;rft.artnum=&amp;rft.au=Luger+K&amp;rft.au=M%C3%A4der+AW&amp;rft.au=Richmond+RK&amp;rft.au=Sargent+DF&amp;rft.au=Richmond+TJ&amp;rfe_dat=bpr3.included=1;bpr3.tags=Biology">Luger K, Mäder AW, Richmond RK, Sargent DF, &amp; Richmond TJ (1997). Crystal structure of the nucleosome core particle at 2.8 A resolution. <span style="font-style: italic;">Nature, 389</span> (6648), 251-60 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/9305837" rev="review">9305837</a> <strong>PDB ID: 1AOI </strong></span></p> <p>6. <span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&amp;rft_id=info%3Apmid%2F15100411&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=Molecular+recognition+of+the+nucleosomal+%22supergroove%22.&amp;rft.issn=0027-8424&amp;rft.date=2004&amp;rft.volume=101&amp;rft.issue=18&amp;rft.spage=6864&amp;rft.epage=9&amp;rft.artnum=&amp;rft.au=Edayathumangalam+RS&amp;rft.au=Weyermann+P&amp;rft.au=Gottesfeld+JM&amp;rft.au=Dervan+PB&amp;rft.au=Luger+K&amp;rfe_dat=bpr3.included=1;bpr3.tags=Biology">Edayathumangalam RS, Weyermann P, Gottesfeld JM, Dervan PB, &amp; Luger K (2004). Molecular recognition of the nucleosomal "supergroove". <span style="font-style: italic;">Proceedings of the National Academy of Sciences of the United States of America, 101</span> (18), 6864-9 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/15100411" rev="review">15100411</a> <strong>PDB ID: 1S32</strong></span></p> <p><a href="https://itunes.apple.com/us/app/molecule-world/id863565223?mt=8">Molecule World™</a> was developed with funding from the National Science Foundation (SBIR IIP 1315426).  Any opinions, findings, conclusions, or recommendations expressed on this website are those of the authors and do not necessarily represent the official views, opinions, or policy of the National Science Foundation.</p> </div> <span><a title="View user profile." href="/author/finchtalk" lang="" about="/author/finchtalk" typeof="schema:Person" property="schema:name" datatype="">finchtalk</a></span> <span>Tue, 05/27/2014 - 04:47</span> <div class="field field--name-field-blog-tags field--type-entity-reference field--label-inline"> <div class="field--label">Tags</div> <div class="field--items"> <div class="field--item"><a href="/tag/genetics-molecular-biology" hreflang="en">Genetics &amp; Molecular Biology</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> <div class="field--item"><a href="/tag/ipad-apps" hreflang="en">iPad apps</a></div> <div class="field--item"><a href="/tag/mmdb" hreflang="en">MMDB</a></div> <div class="field--item"><a href="/tag/molecular-structures" hreflang="en">molecular structures</a></div> <div class="field--item"><a href="/tag/molecule-world" hreflang="en">Molecule World</a></div> <div class="field--item"><a href="/tag/dna-structures" hreflang="en">DNA structures</a></div> <div class="field--item"><a href="/tag/nucleosomes" hreflang="en">nucleosomes</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> </div> </div> <div class="field field--name-field-blog-categories field--type-entity-reference field--label-inline"> <div class="field--label">Categories</div> <div class="field--items"> <div class="field--item"><a href="/channel/technology" hreflang="en">Technology</a></div> </div> </div> <section> <article data-comment-user-id="0" id="comment-1903263" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1401296642"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>Nucléosomes discovered in 1997 ? Joking I hope !<br /> I have told about in 1967 as I studied in an husbandry School ! We made Caryotypes and Cheched Genes Zones in some little flies ! I agree that since some progress have occured ... !!!</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903263&amp;1=default&amp;2=en&amp;3=" token="BajrXaHD5iDZ_Eg0RMg5VeCX0gaikjb5qvFlScaOTSE"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">BEAUSSART ERIC (not verified)</span> on 28 May 2014 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903263">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="105" id="comment-1903264" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1401296959"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>That's not what we wrote.</p> <p>Yes, nucleosomes have been known for a long time but the first crystal structure wasn't published until 1997.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903264&amp;1=default&amp;2=en&amp;3=" token="GOL3LvE3Om8ubgHRoXXyE9gdB81vpfMtY2Dky9PQPZc"></drupal-render-placeholder> </div> <footer> <em>By <a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a> on 28 May 2014 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903264">#permalink</a></em> <article typeof="schema:Person" about="/author/sporte"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/author/sporte" hreflang="en"><img src="/files/styles/thumbnail/public/pictures/59121-arsenic_protein-150x150-120x120.png?itok=o0ajJdDI" width="100" height="100" alt="Profile picture for user sporte" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> </section> <ul class="links inline list-inline"><li class="comment-forbidden"><a href="/user/login?destination=/digitalbio/2014/05/27/nucleosomes-keep-dna-from-reaching-sun%23comment-form">Log in</a> to post comments</li></ul> Tue, 27 May 2014 08:47:24 +0000 finchtalk 69960 at https://scienceblogs.com What Happens at the End? https://scienceblogs.com/digitalbio/2014/05/05/what-happens-at-the-end <span>What Happens at the End?</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><div> <div style="width: 250px;float:right;"><img class=" " src="http://upload.wikimedia.org/wikipedia/commons/9/93/Dnareplication.png" alt="" width="240" height="219" /> Replication fork -  <a href="http://en.wikipedia.org/wiki/Telomere">http://en.wikipedia.org/wiki/Telomere</a>. </div> </div> <p>Organisms with linear chromosomes have to solve the problem that DNA replication makes them shorter. This is due to the fact that DNA polymerase can only add bases to the terminal 3'-OH of a DNA chain. The DNA replication initiation complex uses RNA primers to provide the initial 3'-OH and to initiate "lagging" strand synthesis.  While one strand can be copied all the way to the end of a chromosome, the other, lagging strand, must be primed at short intervals in order to provide a 3' OH group for DNA polymerase as the replication fork advances through a chromosome.  The problem at the end of a chromosome then is that the lagging strand has nothing for the primer to bind to. Without some kind of solution,  each replication cycle would result in a shorter chromosome.</p> <p>Telomeres solve this problem. And, their molecules have cool structures.</p> <p>My recent post on <a title="The A, B, Z’s of DNA" href="http://scienceblogs.com/digitalbio/2014/04/25/the-a-b-zs-of-dna/">DNA structures</a> inspired an entire group of students to ask questions and comment. Some wanted to know about additional kinds of DNA structures that occur in the natural world. Telomeres are one kind of example. They contain short segments of repeated DNA sequences and were first observed by Elizabeth Blackburn in 1975[1]. The repeated sequences can form quadraplex (4-chain) DNA structures, but the significance of their role in maintaining chromosome length was not understood until 1984 when the telomerase enzyme was discovered.</p> <p style="text-align: center;">NMR solution structure of Tetrahymena telomeric repeats [2].</p> <table align="center"><tbody><tr><td> <div style="width: 260px;"><a href="/files/digitalbio/files/2014/05/IMG_0165.jpg"><img class=" wp-image-989 " src="http://scienceblogs.com/digitalbio/files/2014/05/IMG_0165-291x300.jpg" alt="quadraplex" width="250" height="250" /></a> element coloring viewed head on </div> </td> <td> <div style="width: 260px;"><a href="/files/digitalbio/files/2014/05/IMG_0164.jpg"><img class=" wp-image-988 " src="http://scienceblogs.com/digitalbio/files/2014/05/IMG_0164-291x300.jpg" alt="quadraplex" width="250" height="250" /></a> molecule coloring viewed head on </div> </td> </tr><tr><td> <div style="width: 260px;"><a href="/files/digitalbio/files/2014/05/IMG_0167.jpg"><img class=" wp-image-991" src="http://scienceblogs.com/digitalbio/files/2014/05/IMG_0167-291x300.jpg" alt="quadraplex" width="250" height="250" /></a> element coloring viewed from the side </div> </td> <td> <div style="width: 260px;"><a href="/files/digitalbio/files/2014/05/IMG_0166.jpg"><img class=" wp-image-990" src="http://scienceblogs.com/digitalbio/files/2014/05/IMG_0166-291x300.jpg" alt="quadraplex" width="250" height="250" /></a> molecule coloring viewed from the side </div> </td> </tr></tbody></table><p>Telomerase is the enzyme that "lengthens" the ends of chromosomes to provide DNA sequences for priming the lagging strand during DNA synthesis and its discovery, by Blackburn along with Carol Greider and Jack Szostak, led to the Nobel Prize in Physiology or Medicine in 2009 [3].  The enzyme, a ribonucleoprotein complex, is actually a reverse transcriptase that contains an embedded RNA molecule that provides a template for synthesizing short stretches of DNA at the chromosome's end.</p> <p style="text-align: center;">NMR solution structure of the telomerase RNA from Medaka [4].</p> <table align="center"><tbody><tr><td> <div style="width: 245px;"><a href="/files/digitalbio/files/2014/05/IMG_0182.jpg"><img class="size-medium wp-image-997" src="http://scienceblogs.com/digitalbio/files/2014/05/IMG_0182-235x300.jpg" alt="RNA" width="235" height="300" /></a> Space fill RNA with element coloring </div> </td> <td> <div style="width: 245px;"><a href="/files/digitalbio/files/2014/05/IMG_0168.jpg"><img class="size-medium wp-image-992" src="http://scienceblogs.com/digitalbio/files/2014/05/IMG_0168-235x300.jpg" alt="RNA" width="235" height="300" /></a> RNA with residue coloring </div> </td> </tr></tbody></table><p style="text-align: center;">Telomerase catalytic core with RNA [5]</p> <table align="center"><tbody><tr><td> <div style="width: 245px;"><img class=" wp-image-995" style="line-height: 1.5em;" src="http://scienceblogs.com/digitalbio/files/2014/05/IMG_0171-291x300.jpg" alt="telomerase" width="235" height="235" /> Telomerase with RNA, element coloring </div> </td> <td> <div style="width: 245px;"><a style="line-height: 1.5em;" href="/files/digitalbio/files/2014/05/IMG_0170.jpg"><img class=" wp-image-994" src="http://scienceblogs.com/digitalbio/files/2014/05/IMG_0170-291x300.jpg" alt="telomerase" width="235" height="235" /></a> Telomerase with RNA, element coloring </div> </td> </tr></tbody></table><p><span style="line-height: 1.5em;">1. Blackburn, E., &amp; Gall, J. (1978). A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena </span><span style="font-style: italic;">Journal of Molecular Biology, 120</span><span style="line-height: 1.5em;"> (1), 33-53 DOI: </span><a style="line-height: 1.5em;" href="http://dx.doi.org/10.1016/0022-2836(78)90294-2" rev="review">10.1016/0022-2836(78)90294-2</a></p> <p><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Nucleic+Acids+Research&amp;rft_id=info%3Adoi%2F10.1093%2Fnar%2Fgki160&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=i-motif+solution+structure+and+dynamics+of+the+d%28AACCCC%29+and+d%28CCCCAA%29+tetrahymena+telomeric+repeats&amp;rft.issn=1362-4962&amp;rft.date=2005&amp;rft.volume=33&amp;rft.issue=1&amp;rft.spage=213&amp;rft.epage=224&amp;rft.artnum=http%3A%2F%2Fnar.oxfordjournals.org%2Flookup%2Fdoi%2F10.1093%2Fnar%2Fgki160&amp;rft.au=Esmaili%2C+N.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Biology">2. <strong>PDB ID: 1YBN</strong> - Esmaili, N. (2005). i-motif solution structure and dynamics of the d(AACCCC) and d(CCCCAA) tetrahymena telomeric repeats <span style="font-style: italic;">Nucleic Acids Research, 33</span> (1), 213-224 DOI: <a href="http://dx.doi.org/10.1093/nar/gki160" rev="review">10.1093/nar/gki160</a></span></p> <p><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Angewandte+Chemie+International+Edition&amp;rft_id=info%3Adoi%2F10.1002%2Fanie.201002387&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=Telomeres+and+Telomerase%3A+The+Means+to+the+End+%28Nobel+Lecture%29&amp;rft.issn=14337851&amp;rft.date=2010&amp;rft.volume=49&amp;rft.issue=41&amp;rft.spage=7405&amp;rft.epage=7421&amp;rft.artnum=http%3A%2F%2Fdoi.wiley.com%2F10.1002%2Fanie.201002387&amp;rft.au=Blackburn%2C+E.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Biology">3. Blackburn, E. (2010). Telomeres and Telomerase: The Means to the End (Nobel Lecture) <span style="font-style: italic;">Angewandte Chemie International Edition, 49</span> (41), 7405-7421 DOI: <a href="http://dx.doi.org/10.1002/anie.201002387" rev="review">10.1002/anie.201002387</a></span></p> <p><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Nucleic+Acids+Research&amp;rft_id=info%3Adoi%2F10.1093%2Fnar%2Fgkt1276&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=Structure+and+sequence+elements+of+the+CR4%2F5+domain+of+medaka+telomerase+RNA+important+for+telomerase+function&amp;rft.issn=0305-1048&amp;rft.date=2013&amp;rft.volume=42&amp;rft.issue=5&amp;rft.spage=3395&amp;rft.epage=3408&amp;rft.artnum=http%3A%2F%2Fnar.oxfordjournals.org%2Flookup%2Fdoi%2F10.1093%2Fnar%2Fgkt1276&amp;rft.au=Kim%2C+N.&amp;rft.au=Zhang%2C+Q.&amp;rft.au=Feigon%2C+J.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Biology">4. <strong>PDB ID: 2MHI</strong> - Kim, N., Zhang, Q., &amp; Feigon, J. (2013). Structure and sequence elements of the CR4/5 domain of medaka telomerase RNA important for telomerase function <span style="font-style: italic;">Nucleic Acids Research, 42</span> (5), 3395-3408 DOI: <a href="http://dx.doi.org/10.1093/nar/gkt1276" rev="review">10.1093/nar/gkt1276</a></span></p> <p><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Molecular+Cell&amp;rft_id=info%3Adoi%2F10.1016%2Fj.molcel.2012.05.018&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=Structural+Basis+for+Telomerase+RNA+Recognition+and+RNP+Assembly+by+the+Holoenzyme+La+Family+Protein+p65&amp;rft.issn=10972765&amp;rft.date=2012&amp;rft.volume=&amp;rft.issue=&amp;rft.spage=&amp;rft.epage=&amp;rft.artnum=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1097276512004029&amp;rft.au=Singh%2C+M.&amp;rft.au=Wang%2C+Z.&amp;rft.au=Koo%2C+B.&amp;rft.au=Patel%2C+A.&amp;rft.au=Cascio%2C+D.&amp;rft.au=Collins%2C+K.&amp;rft.au=Feigon%2C+J.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Biology">5. <strong>PDB ID: 2ERD</strong> - Singh, M., Wang, Z., Koo, B., Patel, A., Cascio, D., Collins, K., &amp; Feigon, J. (2012). Structural Basis for Telomerase RNA Recognition and RNP Assembly by the Holoenzyme La Family Protein p65 <span style="font-style: italic;">Molecular Cell</span> DOI: <a href="http://dx.doi.org/10.1016/j.molcel.2012.05.018" rev="review">10.1016/j.molcel.2012.05.018</a></span></p> <p>The pictures were made with <a title="Get Molecule World" href="https://itunes.apple.com/us/app/molecule-world/id863565223?ls=1&amp;mt=8" target="_blank">Molecule World</a> on the iPad. If you want to see these structures for yourself, you can find Molecule World in the iTunes store.</p> <p><a href="https://itunes.apple.com/us/app/molecule-world/id863565223?mt=8">Molecule World™</a> was developed with funding from the National Science Foundation (SBIR IIP 1315426).  Any opinions, findings, conclusions, or recommendations expressed on this website are those of the authors and do not necessarily represent the official views, opinions, or policy of the National Science Foundation.</p> </div> <span><a title="View user profile." href="/author/finchtalk" lang="" about="/author/finchtalk" typeof="schema:Person" property="schema:name" datatype="">finchtalk</a></span> <span>Mon, 05/05/2014 - 06:40</span> <div class="field field--name-field-blog-tags field--type-entity-reference field--label-inline"> <div class="field--label">Tags</div> <div class="field--items"> <div class="field--item"><a href="/tag/genetics-molecular-biology" hreflang="en">Genetics &amp; Molecular Biology</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> <div class="field--item"><a href="/tag/ipad-apps" hreflang="en">iPad apps</a></div> <div class="field--item"><a href="/tag/molecular-structures" hreflang="en">molecular structures</a></div> <div class="field--item"><a href="/tag/molecule-world" hreflang="en">Molecule World</a></div> <div class="field--item"><a href="/tag/dna" hreflang="en">DNA</a></div> <div class="field--item"><a href="/tag/telomeres" hreflang="en">telomeres</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> </div> </div> <section> </section> <ul class="links inline list-inline"><li class="comment-forbidden"><a href="/user/login?destination=/digitalbio/2014/05/05/what-happens-at-the-end%23comment-form">Log in</a> to post comments</li></ul> Mon, 05 May 2014 10:40:46 +0000 finchtalk 69959 at https://scienceblogs.com $1000 Genomes for $2000 https://scienceblogs.com/digitalbio/2014/01/27/1000-genomes-for-2000 <span>$1000 Genomes for $2000</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><p><span style="float: left; padding: 5px;"><a href="http://www.researchblogging.org"><img style="border: 0;" alt="ResearchBlogging.org" src="http://www.researchblogging.org/public/citation_icons/rb2_large_gray.png" /></a></span>Getting an accurate genome sequence requires that you collect the data at least twice argue Robasky, Lewis, and Church in their recent opinion piece in Nat. Rev. Genetics [1].</p> <p>The DNA sequencing world kicked off 2014 with an audacious start. Andrew Pollack ran an article in the New York Times implying that 100,000 genomes will be the new norm in human genome sequencing projects [2]. The article focused on a collaboration between Regeneron and Geisinger Health in which they plan to sequence the exomes (the ~2% of the genome that encodes proteins and some non-coding RNA) of 100,000 individuals. In addition to this project, several others were cited in the article.</p> <p>Next, Illumina claimed they can <a title="Illumina press release" href="http://investor.illumina.com/phoenix.zhtml?c=121127&amp;p=irol-newsArticle&amp;ID=1890696&amp;highlight=">achieve the $1000 genome</a> at the annual JP Morgan investor conference when they introduced their new sequencing instrument, the HiSeq X Ten. Ten is the magic number because you must buy ten, at $1 million/instrument, to have the opportunity for $1000 genomes. Illumina claims their $1000 cost includes sample prep and amortization costs. The folks at the AllSeq blog estimate that the <a href="//blog.allseq.com/1000-genome-72m">total investment is really $72 million</a> since it will take 72 genomes, collected over four years, to achieve the amortized costs of $1000 per genome.</p> <p>Unfortunately the above estimates are based on getting data from samples that are sequenced only once. Therein lies the rub. According to Robasky and team, sequencing genomes with high accuracy requires that they be sequenced, minimally, in duplicate. While some sequencing technologies claim they can produce data with errors as low at one in 10 million bases, a six billion genome sequence will still contain thousands of false positive variants. Several aspects of the sequencing process contribute to this error including purifying DNA, preparing DNA for sequencing, collecting sequence data, and comparing the resulting data to the reference sequence to identify variants (bases that differ between sample and reference).</p> <p>The authors how explain that some errors occur through random statistical variation (stochasitc) while others occur because of systematic biases in the different processes, and propose that collecting data in a replicated fashion is a cost effective way to reduce errors. Indeed, a current standard of practice is confirm variants observed by massively parallel next generation sequencing (NGS) by sequencing small regions containing the variant using capillary electrophoresis (Sanger). This is an expensive approach because it requires individual regions be isolated and sequenced in more laborious ways. As NGS sequencing costs drop, however, labor intensive confirmation methods become less attractive, and replicates become more feasible.</p> <p>The paper describes four different kinds of assay replication methods: read depth (oversampling), technical, biological, and cross-platform, and discussed their strengths and weaknesses in term of error reduction and cost. The authors also describe the kinds of errors that have been observed. However, relative to technical advancements, these observations are out of date and published analyses of current error sources are lacking. Some issues continue to exist, others may have been solved, and new ones are likely, so labs establishing sequencing services, especially in clinical arenas, need to have strategies to identify and reduce errors in the data. Finally, the authors make an additional important point that errors related to data processing, limitations of read (collected sequence) length and completeness of reference materials cannot be addressed by replicates alone. New technological solutions will be needed.</p> <p><strong>So, what does this mean?</strong></p> <div style="width: 245px;float:left;"><a href="http://www.genome.gov/sequencingcosts/"><img class=" " style="padding-right: 5px;" alt="" src="http://www.genome.gov/images/content/cost_per_genome_apr.jpg" width="235" height="176" /></a> Human sequencing costs </div> <p>First, DNA sequencing costs (as tracked by the National Human Genome Research Institute [NHGRI]), which have held constant at about $6000/genome since April 2012, may  drop with Illumina’s new instruments. However obtaining a $1000 genome requires a volume-based model and a significant investment in optimization. Even then, obtaining highly accurate, high confidence data, will require replicates, perhaps several kinds, that differ in purpose and range in cost. Second, to truly understand sequence variation in the human population, very large studies , on the order of 100,000 individuals, are needed. Third, the current definition of a $1000 genome is simply the cost of collecting a human genome’s equivalence worth of data without deep data analysis.  This practice results in genome sequences are neither whole, nor understood. The good news is, despite the substantial investment (around $100 million) required, sequencing a few hundred thousand genomes is only a fraction of  the cost of the first genome (~$2.7 billion). Perhaps large-scale exome sequencing projects [2] seeking to understand the relationship between very small regions of sequence variation their impact on health and disease can now consider more realistic genome-wide approaches.</p> <p><strong>References:</strong></p> <p>[1] <span title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Nature+Reviews+Genetics&amp;rft_id=info%3Adoi%2F10.1038%2Fnrg3655&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=The+role+of+replicates+for+error+mitigation+in+next-generation+sequencing.&amp;rft.issn=&amp;rft.date=2014&amp;rft.volume=&amp;rft.issue=&amp;rft.spage=&amp;rft.epage=&amp;rft.artnum=&amp;rft.au=Robasky%2C+K.&amp;rft.au=Lewis%2C+N.+E.%2C&amp;rft.au=Church%2C+G.+M.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Biology">Robasky, K., Lewis, N. E.,, &amp; Church, G. M. (2014). The role of replicates for error mitigation in next-generation sequencing. <span style="font-style: italic;">Nature Reviews Genetics</span> DOI: <a href="http://dx.doi.org/10.1038/nrg3655" rev="review">10.1038/nrg3655</a></span></p> <p>[2] Pollack, B. A. (2014, January 13). Aiming to push genomics forward in new study. <em>The New York Times</em>.</p> </div> <span><a title="View user profile." href="/author/finchtalk" lang="" about="/author/finchtalk" typeof="schema:Person" property="schema:name" datatype="">finchtalk</a></span> <span>Mon, 01/27/2014 - 16:00</span> <div class="field field--name-field-blog-tags field--type-entity-reference field--label-inline"> <div class="field--label">Tags</div> <div class="field--items"> <div class="field--item"><a href="/tag/genetics-molecular-biology" hreflang="en">Genetics &amp; Molecular Biology</a></div> <div class="field--item"><a href="/tag/genome" hreflang="en">Genome</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> <div class="field--item"><a href="/tag/next-generation-dna-sequencing" hreflang="en">Next Generation DNA sequencing</a></div> </div> </div> <section> <article data-comment-user-id="0" id="comment-1903230" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1390943357"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>Thanks for this insightful analysis, Sandra! While I am a co-first author on the NRG article, I'm not the corresponding author, so I hope you will nonetheless allow me to clarify and comment: </p> <p>Claims have been made about technologies that can reduce error rates to as low as one in a several million bases; however, even such a low rate requires researchers to sift through hundreds (not thousands) of false positives. More commonplace technology have published error-rates that are orders of magnitude higher, yielding thousands of what I will call "sources of variation" in the over 3 billion base pairs from a typical whole human genome. These sources may be from biologically-relevant somatic variation which obfuscates the genotype, or they may be from error. Either way, if the goal is genotyping, then the analyst typically will threshold at a p-value derived from base-calling scores. The alternative thresholding mechanism offered in the paper also accounts for other sources of error that might not be quantified by base-calling scores, and it is a method that can be used for a replicate-set from any platform. The implication is that perhaps three 20x replicates are better than a single 60x run. I anticipate the day that single-cell sequencing becomes commonplace, at which point perhaps one can use replicates to distinguish between somatic variation and sequencer error, but until then, deep sequencing will remain the most common method for finding somatic variation.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903230&amp;1=default&amp;2=en&amp;3=" token="nOLGIaB3UZBIJtrLa04Pcb86turyPN2YGL6YQtjNKJg"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">Kimberly Robasky (not verified)</span> on 28 Jan 2014 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903230">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="106" id="comment-1903231" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1391124844"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>Hi Kimberly, thanks for the comment and additional details.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903231&amp;1=default&amp;2=en&amp;3=" token="M6eUC83kv-h5PttUMFl8P6WN1YpwthqOVGQXUPMbC3k"></drupal-render-placeholder> </div> <footer> <em>By <a title="View user profile." href="/author/finchtalk" lang="" about="/author/finchtalk" typeof="schema:Person" property="schema:name" datatype="">finchtalk</a> on 30 Jan 2014 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903231">#permalink</a></em> <article typeof="schema:Person" about="/author/finchtalk"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/author/finchtalk" hreflang="en"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> </section> <ul class="links inline list-inline"><li class="comment-forbidden"><a href="/user/login?destination=/digitalbio/2014/01/27/1000-genomes-for-2000%23comment-form">Log in</a> to post comments</li></ul> Mon, 27 Jan 2014 21:00:45 +0000 finchtalk 69955 at https://scienceblogs.com Genomes with benefits https://scienceblogs.com/digitalbio/2011/10/02/genomes-with-benefits <span>Genomes with benefits</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><p>For the past few days I've been avidly following Daniel MacArthur's tweets from the Personal Genome Conference at Cold Spring Harbor(<a href="http://twitter.com/#!/dgmacarthur">@dgmacarthur </a><a href="http://twitter.com/#!/search/%23cshlpg">#cshlpg</a>). </p> <p>The Personal Genomics tweets aren't just interesting because of the science, they're interesting because MacArthur and others have started to take on the conventional dogma in genetic ethics. </p> <p>For years, there has been a strong message from the clinical genetics and genetics education community that genetic information is dangerous.</p> <!--more--><p>Unlike the other medical tests we're continually urged to get (<em>mammograms, blood pressure readings, sugar, colonoscopies</em>) genetic tests are presented, at least in teaching materials, as <i>risky</i>. According to many teaching materials, you should not get a genetic test, until you've identified all the stake holders, and weighed all the pros and cons. Imagine if doctors used followed these procedures before reading someone's blood pressure or taking their temperature. The implication isn't stated, but the underlying message is clear: <i>Genetic tests are different and more dangerous than conventional medical procedures</i>.</p> <p>Ironically, much of the negative atmosphere around genetic information seems to have originated from ELSI. ELSI was a commitment on the part of the NIH to use 1% of the money allocated to sequencing the human genome to fund studies on the ethical, legal, and social implications of the human genome project. </p> <p>Instead, ELSI has produced several curricular materials that present genome sequencing as a "bad idea." The biggest consequence of ELSI has been to turn the desire for one's own genomic information into something shameful.   </p> <p>People who get their DNA sequences are equated with skydivers, speed racers, and winners of the Darwin awards. All the signs say "<i>Warning!! You are engaging in risky behavior that could endanger your family, job, and insurance policy</i>."</p> <p></p> <p><b>The top reasons for discouraging genetic testing</b></p> <p>The usual reasons that geneticists give for discouraging people from seeking genetic testing are:</p> <p>- the results are too complicated for most people to understand (<i>most people are too stupid?</i>)</p> <p>- the risks outweigh the benefits  (<i>This could be true, but we rarely talk about the benefits, and we obsess about the risks.</i>)</p> <p>- it's expensive (<i>According to Atul Butte, by way of Daniel MacArthur's tweets, a colonscopy costs $6000.  This is now 6x more expensive then having 23andme sequence your exome, plus you would get far more information</i>.)</p> <p></p> <p><b>It's not just the education community</b></p> <p>Some of tweets from MacArthur were on stories from Gholson Lyon on being unable to share findings from Next Generation DNA sequencing studies with patients. </p> <p>Patients in clinical studies must give their consent and acknowledge that they understand the risks of the study in order to participate. The forms that are used for consent are designed to protect patients and minimize risks.</p> <p> A problem with some clinical studies is that occasionally the researchers find medical problems in the participants that weren't known before the study. These kinds of findings are becoming more common with studies that sequence the entire genome. Unfortunately, the common practice has been to avoid returning this kind of "<i>incidental</i>" information back to the patients. After all, they didn't give their consent to receive it.</p> <p> MacAthur tweeted one story from Gholson Lyon where the researchers learned that a woman in a study, who was 4 months pregnant, was a carrier for a lethal disease. They weren't allowed to tell her this because of the IRB constraints, and the affected baby died. According to MacArthur, " ... <i>this emphasizes the moral horror of blocking return of research findings.</i>"</p> <p><b><br /> Out of the mouths of babes</b></p> <p> A teenage conference attendee spurred one of MacArthur's most intriguing tweets:</p> <p> "<i>Anne West (only healthy teenager I know with a genome sequence) asks about consent forms: shouldn't they include risks AND benefits? #cshlpg</i>"</p> <p> According to @finchtalk, West, apparently used Next Generation DNA sequencing, to determine the DNA sequence of her own genome and that of other family members as part of a high school science project. </p> <p>  <br />West makes a good point. </p> <p><i>Why don't we give equal time to talking about the benefits?</i></p> <p> Maybe it's time to acknowledge that genetic information is just like any other kind of medical information. Deciding not to get a test, never makes a problem go away. </p> </div> <span><a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a></span> <span>Sun, 10/02/2011 - 11:56</span> <div class="field field--name-field-blog-tags field--type-entity-reference field--label-inline"> <div class="field--label">Tags</div> <div class="field--items"> <div class="field--item"><a href="/tag/genetics-molecular-biology" hreflang="en">Genetics &amp; Molecular Biology</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> <div class="field--item"><a href="/tag/next-generation-dna-sequencing" hreflang="en">Next Generation DNA sequencing</a></div> <div class="field--item"><a href="/tag/elsi" hreflang="en">ELSI</a></div> <div class="field--item"><a href="/tag/genetic-testing" hreflang="en">genetic testing</a></div> <div class="field--item"><a href="/tag/personal-genomics" hreflang="en">personal genomics</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> <div class="field--item"><a href="/tag/next-generation-dna-sequencing" hreflang="en">Next Generation DNA sequencing</a></div> </div> </div> <div class="field field--name-field-blog-categories field--type-entity-reference field--label-inline"> <div class="field--label">Categories</div> <div class="field--items"> <div class="field--item"><a href="/channel/medicine" hreflang="en">Medicine</a></div> </div> </div> <section> <article data-comment-user-id="0" id="comment-1903095" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1317579215"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>Huh, interesting. I would have thought the primary risk of getting your genome sequenced is that someone else might get their hands on the data and use it against you.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903095&amp;1=default&amp;2=en&amp;3=" token="Q5J2wEUs8cEd3IU60VRPXZZu2TQPlM6aUhdcl_c6cqE"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">Matthew Cline (not verified)</span> on 02 Oct 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903095">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="105" id="comment-1903096" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1317579814"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>I think making your genetic information public would be equivalent to making your other health records public. Some information is best kept private. </p> <p>Keeping information private though, is different from never getting it in the first place.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903096&amp;1=default&amp;2=en&amp;3=" token="T7d_5PVAt0cvNbpjVEK9IzCSNQYWWPMDzQwClXpIvS4"></drupal-render-placeholder> </div> <footer> <em>By <a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a> on 02 Oct 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903096">#permalink</a></em> <article typeof="schema:Person" about="/author/sporte"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/author/sporte" hreflang="en"><img src="/files/styles/thumbnail/public/pictures/59121-arsenic_protein-150x150-120x120.png?itok=o0ajJdDI" width="100" height="100" alt="Profile picture for user sporte" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="0" id="comment-1903097" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1317587549"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>What I meant was, that if I was to get a warning about having my genome sequenced, I would expect the warning to be "some genome sequencing companies might sell your genome to insurance companies", or something like that. The actual warning being so different than that surprises me.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903097&amp;1=default&amp;2=en&amp;3=" token="ySNmNtUhLpGEqQjlE51iyEFyYRrO-oubrNCrySODOAQ"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">Matthew Cline (not verified)</span> on 02 Oct 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903097">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="105" id="comment-1903098" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1317588225"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>I see.</p> <p>Well, if your genome was sequenced as part of a medically prescribed procedure, the insurance company would already own it. </p> <p>Your doctor is required by law to give all your medical information to your insurance company. So, they already own all your medical information.</p> <p>The only way that you can own your genomic information is if you get this information from a lab and pay for it yourself, without involving your insurance company or your doctor. I don't think the companies that perform those kinds of services go out and resell that information.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903098&amp;1=default&amp;2=en&amp;3=" token="k9xSbpcS3rCseT-Vct1Ehwpg5KwfXRMXXckRLYnQCVE"></drupal-render-placeholder> </div> <footer> <em>By <a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a> on 02 Oct 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903098">#permalink</a></em> <article typeof="schema:Person" about="/author/sporte"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/author/sporte" hreflang="en"><img src="/files/styles/thumbnail/public/pictures/59121-arsenic_protein-150x150-120x120.png?itok=o0ajJdDI" width="100" height="100" alt="Profile picture for user sporte" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="0" id="comment-1903099" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1317634440"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>Actually, the conventional screening are as dangerous, if not more so than genetic tests. Ever heard of overdiagnosis? It could ruin your life and insurance. <a href="http://en.wikipedia.org/wiki/Overdiagnosis">http://en.wikipedia.org/wiki/Overdiagnosis</a><br /> The geneticists are just being honest about it. A little knowledge...</p> <p>"Unlike the other medical tests we're continually urged to get (mammograms, blood pressure readings, sugar, colonoscopies) genetic tests are presented, at least in teaching materials, as risky. According to many teaching materials, you should not get a genetic test, until you've identified all the stake holders, and weighed all the pros and cons. Imagine if doctors used followed these procedures before reading someone's blood pressure or taking their temperature. The implication isn't stated, but the underlying message is clear: Genetic tests are different and more dangerous than conventional medical procedures."</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903099&amp;1=default&amp;2=en&amp;3=" token="sa7Tpk0ooYaWsZOjvssn3j9l0tBFuwqo8cgSBScK4Fc"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">XYZ (not verified)</span> on 03 Oct 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903099">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="105" id="comment-1903100" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1317637073"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>There is a difference between a diagnosis and a test. The test simply provides information.</p> <p>A diagnosis is the interpretation of test results together with other information. Doctors can make mistakes in interpreting test results. Their mistakes can lead to complications.</p> <p>But an incorrect diagnosis is a mistake made by a doctor. It's not the same thing as having a medical test.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903100&amp;1=default&amp;2=en&amp;3=" token="cljy4ESEc2z4wdiy9DtMsnrfR_6F-UkTjO3SiGYeH7c"></drupal-render-placeholder> </div> <footer> <em>By <a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a> on 03 Oct 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903100">#permalink</a></em> <article typeof="schema:Person" about="/author/sporte"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/author/sporte" hreflang="en"><img src="/files/styles/thumbnail/public/pictures/59121-arsenic_protein-150x150-120x120.png?itok=o0ajJdDI" width="100" height="100" alt="Profile picture for user sporte" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="0" id="comment-1903101" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1317637840"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>Regarding insurance risks (at least in the US) - isn't that what GINA is all about? <a href="http://en.wikipedia.org/wiki/Genetic_Information_Nondiscrimination_Act">http://en.wikipedia.org/wiki/Genetic_Information_Nondiscrimination_Act</a></p> <p>(I tried to include it as a hyperlink, rather than an ugly url, but it looks like Sb isn't accepting hyperlinks any more)</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903101&amp;1=default&amp;2=en&amp;3=" token="kQXh3uSGianx3MaSQdn3kLNWY2tbq4OVYm-tKblCHP4"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">Ian (not verified)</span> on 03 Oct 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903101">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="0" id="comment-1903102" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1317638316"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>There is another side to this: having spent many years trying to get to the bottom of a medical condition that might be 'inherited'- that is, get a CORRECT diagnosis, was mind-boggling! Doctors just don't know much; they're guessing half the time; they run up tests $$, throw drugs at patients, get cranky and blame patients for their symptoms, and generally behave badly. Even when you get a diagnosis, it's wrong. AND all these diagnosis find their way to insurance companies (and seemingly everywhere else) anyway. </p> <p>I would have been thrilled to have a definitive genetic answer.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903102&amp;1=default&amp;2=en&amp;3=" token="GfDjRj_BLCPP9p-nzvk5K8MBpDyM57JLOTZ85SCjH4I"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">gina rex (not verified)</span> on 03 Oct 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903102">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="0" id="comment-1903103" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1317644263"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>It seems to me that they only increased risk is the risk of being turned down for insurance. The whole concept of "pooled risk" , which is the basis of the insurance industry math models, is at risk be cause now each person can (in theory) be assigned a very accurate INDIVIDUAL risk.<br /> Genomic information as THE major diagnostic tool is well on its way to braod acceptance. The way we pay for healthcare, including the Insurance industry will have to run to catch up. Denying this powerful inexpensive technique is ludicrous, especially if it is only because we do not know how to sell insurance in the brave new world. The cure is out there...<br /> With genome sequencing we can make sense of autism, diabetes and other growing national heath insurance concerns.<br /> It is not risky to know the truth, it is a diagnosis.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903103&amp;1=default&amp;2=en&amp;3=" token="tddpB9o6AsABiA536Bc6p5MjZ87Ix9L04jptUwtlCDo"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">jkittle (not verified)</span> on 03 Oct 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903103">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="0" id="comment-1903104" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1317723900"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>The ELSI funding was actually 3% to 5%.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903104&amp;1=default&amp;2=en&amp;3=" token="RVo6HGv5Czu9rEVdU9jEuoO1R--DgyHn8EPXEuLhJAU"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">John (not verified)</span> on 04 Oct 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903104">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="0" id="comment-1903105" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1317732808"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>My wife received a genetic test in response to something her mother has. My wife tested positive but is completely asymptomatic for the disease which her mother has. She enrolled in a study of the disease and is of particular interest to the study because of her lack of disease symptoms. She was rejected for life insurance by multiple companies as a result of this.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903105&amp;1=default&amp;2=en&amp;3=" token="OzjPOg1bIOc69MhxXrpb86dMWJfUVn3AmcyTHNzR6AA"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">anon (not verified)</span> on 04 Oct 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903105">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="105" id="comment-1903106" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1317735420"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>@anon: That's an unfortunate outcome but it's not unique to genetic tests. Other medical procedures can also find information that affects insurance coverage. We need health care reform.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903106&amp;1=default&amp;2=en&amp;3=" token="MVXeLPa7Hyz0JFm1sVE5-eEtJqIpMiW5k7FzE0W113E"></drupal-render-placeholder> </div> <footer> <em>By <a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a> on 04 Oct 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903106">#permalink</a></em> <article typeof="schema:Person" about="/author/sporte"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/author/sporte" hreflang="en"><img src="/files/styles/thumbnail/public/pictures/59121-arsenic_protein-150x150-120x120.png?itok=o0ajJdDI" width="100" height="100" alt="Profile picture for user sporte" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="0" id="comment-1903107" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1322743528"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>Insurers will prey on any information. They are business operators so it's up to you to decide the risks of testing on the DTC market before taking the test. The moment you decide to take it, you have placed yourself on the risky market and you alone are responsible for defending your interests. Anything else would be paternalistic.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903107&amp;1=default&amp;2=en&amp;3=" token="PnNVN1wtUKPzTSXc581jQItExjACAAEiC4xTOzEd4tY"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">Ruth Saunders (not verified)</span> on 01 Dec 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903107">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="105" id="comment-1903108" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1322772382"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>One of the big differences between DTC genomics and having a clinical test, prescribed by your doctor is that you pay for the test yourself and you own your results. In the US, a test that prescribed by your doctor produces data that is owned by your insurance company.</p> <p>So you have greater protection from insurance issues if you use a DTC company to get your genotype.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903108&amp;1=default&amp;2=en&amp;3=" token="AECxx3SUBx5N8MunnzigCNgxxfCGQop_Nx4ZmZMNDVA"></drupal-render-placeholder> </div> <footer> <em>By <a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a> on 01 Dec 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903108">#permalink</a></em> <article typeof="schema:Person" about="/author/sporte"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/author/sporte" hreflang="en"><img src="/files/styles/thumbnail/public/pictures/59121-arsenic_protein-150x150-120x120.png?itok=o0ajJdDI" width="100" height="100" alt="Profile picture for user sporte" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> </section> <ul class="links inline list-inline"><li class="comment-forbidden"><a href="/user/login?destination=/digitalbio/2011/10/02/genomes-with-benefits%23comment-form">Log in</a> to post comments</li></ul> Sun, 02 Oct 2011 15:56:01 +0000 sporte 69940 at https://scienceblogs.com Strategic plans and genome sequencing https://scienceblogs.com/digitalbio/2011/02/14/strategic-plans-and-genome-seq <span>Strategic plans and genome sequencing</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><p>This morning I attended a "bloggers-only" conference call with Dr. Eric Green and the folks from the NIH Human Genome Research Institute (NHGRI) to hear about NHGRI's new strategic plan. The new plan represents a shift away from viewing the genome through a lens marked "for research use only" and towards the goal of making the genome useful as a clinical tool. As a consequence, we will see a greater emphasis on funding activities that support clinical work. For example, it's not always clear how variations in the genome are related to disease. NHGRI might fund projects that help sort and categorize this information. It's certainly not clear yet what NHGRI should do to help patients and physicians handle the genetic information onslaught, particularly in the area of personal genomics.</p> <p>Personally, I think some of the folks at NHGRI might find it eye-opening if they were to sign up with 23andme and see the sorts of genetic information the general public can get. </p> <p>My family and I all took advantage of the "genetic testing special" last December and mailed 23andme our tubes of spit. Since we got the results, we've had lots of fun figuring out who inherited which alleles from who and learning why some of us can drink coffee at night. We've also spent some time explaining to our kids that some of results are far less meaningful than others and why a 1.1 fold increase in risk for some disorder is not terribly alarming.</p> <p>I have to admit, <a href="https://www.23andme.com/">23andme</a> has some pretty nice videos and education resources.  Getting teenagers to sort through all the information is not easy, but the information is there, if they care to look.</p> <p>Which brings me to the point where I found the conference call a bit disappointing. </p> <p>In the phone call, Dr. Green called out education and training as one of the important cross-cutting themes that must be supported if the benefits of genomics are going to be wide-spread. Genomic information isn't likely to be used widely unless the general public understands those benefits.</p> <p>Since NHGRI doesn't fund many education programs, except at a graduate level, and since the one NIH institute that does fund education (NCRR) is being dismantled, I was interested to know if NHGRI has any plans to take over that role. So, I asked Dr. Green if NHGRI has any specific plans to support genomics education.</p> <p>His answer was longer. The short version was "no." </p> <p>At this point, I really don't know why there's a special box in the strategic report on education and training. Maybe those subjects are only mentioned because we know they're important, not because we plan to do anything. Maybe, like personal genomics, we'll just leave that subject to groups like 23andme.</p> <p><b>Reference<br /></b><br /><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Nature&amp;rft_id=info%3Apmid%2F21307933&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=Charting+a+course+for+genomic+medicine+from+base+pairs+to+bedside.&amp;rft.issn=0028-0836&amp;rft.date=2011&amp;rft.volume=470&amp;rft.issue=7333&amp;rft.spage=204&amp;rft.epage=13&amp;rft.artnum=&amp;rft.au=Green+ED&amp;rft.au=Guyer+MS&amp;rft.au=National+Human+Genome+Research+Institute&amp;rft.au=Overall+leadership&amp;rft.au=Green+ED&amp;rft.au=Guyer+MS&amp;rft.au=Coordination+of+writing+contributions+%28see+Acknowledgements+for+list+of+other+contributors%29&amp;rft.au=Manolio+TA&amp;rft.au=Peterson+JL&amp;rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CBioinformatics%2C+Biotechnology%2C+Genetics%2C+Genomics">Green ED, Guyer MS, National Human Genome Research Institute, Overall leadership, Green ED, Guyer MS, Coordination of writing contributions (see Acknowledgements for list of other contributors), Manolio TA, &amp; Peterson JL (2011). Charting a course for genomic medicine from base pairs to bedside. <span style="font-style: italic;">Nature, 470</span> (7333), 204-13 PMID: <a rev="review" href="http://www.ncbi.nlm.nih.gov/pubmed/21307933">21307933</a></span></p> <p></p> </div> <span><a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a></span> <span>Mon, 02/14/2011 - 09:36</span> <div class="field field--name-field-blog-tags field--type-entity-reference field--label-inline"> <div class="field--label">Tags</div> <div class="field--items"> <div class="field--item"><a href="/tag/genetics-molecular-biology" hreflang="en">Genetics &amp; Molecular Biology</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> <div class="field--item"><a href="/tag/science-education" hreflang="en">Science Education</a></div> <div class="field--item"><a href="/tag/personal-genomics" hreflang="en">personal genomics</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> <div class="field--item"><a href="/tag/science-education" hreflang="en">Science Education</a></div> </div> </div> <section> <article data-comment-user-id="0" id="comment-1903086" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1301371703"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>Nor in Canada! Oh the irony!</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1903086&amp;1=default&amp;2=en&amp;3=" token="BxYSxQgSpr4YRXM-AR8KFeof2TsbKLP9dIkTmvx7Ffs"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">Bayan azdırıcı (not verified)</span> on 29 Mar 2011 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1903086">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> </section> <ul class="links inline list-inline"><li class="comment-forbidden"><a href="/user/login?destination=/digitalbio/2011/02/14/strategic-plans-and-genome-seq%23comment-form">Log in</a> to post comments</li></ul> Mon, 14 Feb 2011 14:36:50 +0000 sporte 69936 at https://scienceblogs.com Exploding graphs and seeing stars https://scienceblogs.com/digitalbio/2010/06/24/exploding-graphs-and-seeing-st-1 <span>Exploding graphs and seeing stars</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><p>One of my hobbies lately has been to get either RNA seq or microarray data from GEO and do quick analyses. Not only is this fun, I can find good examples to use for teaching biology.</p> <p>One of these fun examples comes from some Arabidopsis data. In this experiment, some poor little seedlings were taken out of their happy semi-liquid culture tubes and allowed to dry out. This simulated drought situation isn't exactly dust bowls and hollow-eyed farmers, but the plants don't know that and most likely respond in a similar way. </p> <p><img src="http://scienceblogs.com/digitalbio/wp-content/blogs.dir/460/files/2012/04/i-c248c6c3b10f8c1c09b763545e62cc21-1.jpg" alt="i-c248c6c3b10f8c1c09b763545e62cc21-1.jpg" /></p> <p>We can get a quick idea of how the plants feel about their situation by looking at the data in a volcano plot.</p> <!--more--><p><img src="http://scienceblogs.com/digitalbio/wp-content/blogs.dir/460/files/2012/04/i-b0eb782a4bd269ee0ed9aef4e73977e0-Screen shot 2010-06-24 at 10.18.34 AM.png" alt="i-b0eb782a4bd269ee0ed9aef4e73977e0-Screen shot 2010-06-24 at 10.18.34 AM.png" /></p> <p>These graphs are called "volcano plots" because it looks like data points are spewing out a volcano. There are about 28,000 or so of these spots on this graph. Each spot represents a bit of RNA that was measured in this experiment. When a gene is "expressed," a bit of RNA is produced. We can measure that RNA to find out what changes are happening inside of a cell.</p> <p>We often say that genes are "turned on" when they're expressed (i.e. RNA copies are being made) and "turned off" when RNA copies are no longer produced. We can find out alot of things by measuring the concentration of RNA.</p> <p>On the X axis, in our volcano plot, we see the change in RNA concentration when we compare two conditions. The first condition represents the average results from the control samples (think "happy plants"). The second condition is an average from several samples taken over a 24 hour period where the plants were drying out. I put lots of samples and time points together in the second condition. </p> <p>If a data point falls in the middle of the graph, that means that the RNA levels from those gene are roughly the same in both happy and stressed out plants. These spots are colored gray because I told the software (GeneSifter from <a href="http://www.geospiza.com">Geospiza</a>) that I wanted to see genes whose expression changed at least 1.5 fold.</p> <p>The side that a spot falls on helps us figure out how gene expression changed when plants were drying out. If a gene produced more RNA in a happy plant, it's represented as a blue spot on the left side of the graph. If a gene produced more RNA in a drying plant, we see it represented, in red, on the right side of the graph.</p> <p>Our graph shows us that some genes are turned on in happy plants, and some genes are turned on in stressed plants. GeneSifter also lets me click spots and see what the genes are, but we'll skip that for now. </p> <p>We can also see how much gene expression changed by looking at the distance from the center. Points that are farthest from the center show us genes whose expression changed to a greater extent. </p> <p>The y axis shows us the significance of the result. Points that are higher are more significant. In this case, it means that the measurements were closer together. This graph makes it look like the data from the happy plants is more significant. This is probably because those two samples came from the control plants where the other measurements represent average RNA concentrations from plants sampled at many different time points.</p> <p>Anyway, the RNA measured in the top graph came from the stem and leaves of the plants. </p> <p>Look what happens when we take a look at the roots!</p> <p><img src="http://scienceblogs.com/digitalbio/wp-content/blogs.dir/460/files/2012/04/i-28e16c0dda791fde97f3124510abab2c-Screen shot 2010-06-24 at 10.19.49 AM.png" alt="i-28e16c0dda791fde97f3124510abab2c-Screen shot 2010-06-24 at 10.19.49 AM.png" /></p> <p>Do the graphs look different? What do you think is going on in the drought-stressed roots?</p> </div> <span><a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a></span> <span>Thu, 06/24/2010 - 08:49</span> <div class="field field--name-field-blog-tags field--type-entity-reference field--label-inline"> <div class="field--label">Tags</div> <div class="field--items"> <div class="field--item"><a href="/tag/bioinformatics" hreflang="en">bioinformatics</a></div> <div class="field--item"><a href="/tag/genetics-molecular-biology" hreflang="en">Genetics &amp; Molecular Biology</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> <div class="field--item"><a href="/tag/geo" hreflang="en">GEO</a></div> <div class="field--item"><a href="/tag/microarray-analysis" hreflang="en">microarray analysis</a></div> <div class="field--item"><a href="/tag/plant-biology" hreflang="en">Plant biology</a></div> <div class="field--item"><a href="/tag/arabidopsis" hreflang="en">Arabidopsis</a></div> <div class="field--item"><a href="/tag/drought" hreflang="en">drought</a></div> <div class="field--item"><a href="/tag/microarray-data-analysis" hreflang="en">microarray data analysis</a></div> <div class="field--item"><a href="/tag/scatter-plots" hreflang="en">scatter plots</a></div> <div class="field--item"><a href="/tag/volcano-plots" hreflang="en">volcano plots</a></div> <div class="field--item"><a href="/tag/bioinformatics" hreflang="en">bioinformatics</a></div> <div class="field--item"><a href="/tag/genomics" hreflang="en">genomics</a></div> <div class="field--item"><a href="/tag/plant-biology" hreflang="en">Plant biology</a></div> </div> </div> <section> <article data-comment-user-id="0" id="comment-1902969" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1277382015"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>Assuming that it's array data, are you retrieving raw or normalized data?</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1902969&amp;1=default&amp;2=en&amp;3=" token="QSernTrBX7BkFwa4GBcR3UPzv3Ucl97JWAde-1MlNPA"></drupal-render-placeholder> </div> <footer> <em>By <span lang="" typeof="schema:Person" property="schema:name" datatype="">JohnV (not verified)</span> on 24 Jun 2010 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1902969">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="105" id="comment-1902970" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1277382226"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>The data were normalized with RMA. GeneSifter was also set up to process the data using a t test, the p value cutoff is 0.05.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1902970&amp;1=default&amp;2=en&amp;3=" token="ysGAazspSCzfnM_AgAuP9e3l3UogNEAiHfrndytH_RQ"></drupal-render-placeholder> </div> <footer> <em>By <a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a> on 24 Jun 2010 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1902970">#permalink</a></em> <article typeof="schema:Person" about="/author/sporte"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/author/sporte" hreflang="en"><img src="/files/styles/thumbnail/public/pictures/59121-arsenic_protein-150x150-120x120.png?itok=o0ajJdDI" width="100" height="100" alt="Profile picture for user sporte" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="105" id="comment-1902971" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1277390462"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>I should add - this is microarray data - but you can't assume that from the graph. Genesifter makes the same kinds of graphs with RNA Seq data, too.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1902971&amp;1=default&amp;2=en&amp;3=" token="je77gRH7I6LAIpjQc7uqmKigudvepPplWR8BzKqWRkg"></drupal-render-placeholder> </div> <footer> <em>By <a title="View user profile." href="/author/sporte" lang="" about="/author/sporte" typeof="schema:Person" property="schema:name" datatype="">sporte</a> on 24 Jun 2010 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1902971">#permalink</a></em> <article typeof="schema:Person" about="/author/sporte"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/author/sporte" hreflang="en"><img src="/files/styles/thumbnail/public/pictures/59121-arsenic_protein-150x150-120x120.png?itok=o0ajJdDI" width="100" height="100" alt="Profile picture for user sporte" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> <article data-comment-user-id="0" id="comment-1902972" class="js-comment comment-wrapper clearfix"> <mark class="hidden" data-comment-timestamp="1277497527"></mark> <div class="well"> <strong></strong> <div class="field field--name-comment-body field--type-text-long field--label-hidden field--item"><p>I guess pretty much the same thing that is going on in the stems and leaves, except to a lesser extent because the roots can retain the moisture that they do collect, rather than sharing it with the rest of the plant, and so they do not suffer the drought as badly.</p> </div> <drupal-render-placeholder callback="comment.lazy_builders:renderLinks" arguments="0=1902972&amp;1=default&amp;2=en&amp;3=" token="0oG23VkTHa9gAWwDnibJiB35r4DddEsYd2ypdua4SHc"></drupal-render-placeholder> </div> <footer> <em>By <a rel="nofollow" href="http://uncc.ath.cx" lang="" typeof="schema:Person" property="schema:name" datatype="">Nathan Nifong (not verified)</a> on 25 Jun 2010 <a href="https://scienceblogs.com/taxonomy/term/18254/feed#comment-1902972">#permalink</a></em> <article typeof="schema:Person" about="/user/0"> <div class="field field--name-user-picture field--type-image field--label-hidden field--item"> <a href="/user/0" hreflang="und"><img src="/files/styles/thumbnail/public/default_images/icon-user.png?itok=yQw_eG_q" width="100" height="100" alt="User Image" typeof="foaf:Image" class="img-responsive" /> </a> </div> </article> </footer> </article> </section> <ul class="links inline list-inline"><li class="comment-forbidden"><a href="/user/login?destination=/digitalbio/2010/06/24/exploding-graphs-and-seeing-st-1%23comment-form">Log in</a> to post comments</li></ul> Thu, 24 Jun 2010 12:49:35 +0000 sporte 69920 at https://scienceblogs.com