basics

Shotgun sequencing. Sounds like fun. Speculations on the origin of the phrase I think that this term came from shotgun cloning. In the early days of gene cloning before cDNA, PCR, or electroporation; molecular biologists would break genomic DNA up into lots of smaller pieces, package DNA in lambda phage, transduce E. coli, and hope for the best. Consistent with the shotgun metaphor, we even used to store our microfuge tubes in plastic bullet boxes that my boss found at the sporting goods store. (Apparently this practice was unique to Minnesota, though. When I moved out west for graduate…
This is another great basics topic, and it's also one of my pet peeves. In general, I'm a big science fiction fan, and I grew up in a house where every saturday at 6pm, we all gathered in front of the TV to watch Star Trek. But one thing which Star Trek contributed to our vocabulary, for which I will never forgive Gene Rodenberry, is "Logic". As in, Mr. Spock saying "But that would not be logical.". The reason that this bugs me so much is because it's taught a huge number of people that "logical" means the same thing as "reasonable". Almost every time I hear anyone say that something is…
Considering that several genomes that have been sequenced in the past decade, it seems amazing in retrospect, that the first complete bacterial genome sequence was only published 12 years ago (1). Now, the Genome database at the NCBI lists 450 complete microbial genomes (procaryotes and archea), 1476 genomes from eucaryotes, 2145 viruses, and genome sequences from 407 phage. Much of the methodology used for sequencing DNA is designed to confront one big technical hurdle. That is, we can only determine the sequence of small pieces of DNA at a time. This means that you must break a larger…
Correlation and Causation Yet another of the most abused mathematical concepts is the concept of correlation, along with the related (but different) concept of causation. Correlation is actually a remarkably simple concept, which makes it all the more frustrating to see the nonsense constantly spewed in talking about it. Correlation is a linear relationship between two random variables. Let's look at the pieces of that, to really nail down the meaning of the concept precisely. What's a random variable? A random variable is a rather dreadful misnomer - because it's not actually a…
Time for another sort-of advanced basic. I used some recursive definitions in my explanation of natural numbers and integers. Recursion is a very fundamental concept, but one which many people have a very hard time wrapping their head around. So it's worth taking the time to look at it, and see what it means and how it works. The cleverest definition that I've seen of recursion comes from the Hackers dictionary. In there, it has: recursion n. See {recursion}. Recursion is about defining things in terms of themselves. For what is probably the canonical example, think about the…
One of the interestingly odd things about how people understand math is numbers. It's astonishing to see how many people don't really understand what numbers are, or what different kinds of numbers there are. It's particularly amazing to listen to people arguing vehemently about whether certain kinds of numbers are really "real" or not. Today I'm going to talk about two of the most basic kind of numbers: the naturals and the integers. This is sort of an advanced basics article; to explain things like natural numbers and integers, you can either write two boring sentences, or you can go a…
About a week ago, I offered to answer questions about subjects that I've either worked with, studied or taught. I haven't had many questions yet, but I can certainly answer the ones I've had so far. Today, I'll answer the first question: How do you sequence a genome? Before we get into the technical details, there are some other genomic questions that you might like answered. How much does it cost to sequence a genome? I remember in 2002, when we were at the O'Reilly bioinformatics conference and we heard Lee Hood challenge the DNA sequencing community to lower the costs of genomic…
The margin of error is the most widely misunderstood and misleading concept in statistics. It's positively frightening to people who actually understand what it means to see how it's commonly used in the media, in conversation, sometimes even by other scientists! The basic idea of it is very simple. Most of the time when we're doing statistics, we're doing statistics based on a sample - that is, the entire population we're interested in is difficult to study; so what we try to do is pick a representative subset called a sample. If the subset is truly representative, then the statistics you…
In the effort to help us define a few basic concepts, PZ started out by giving us a nice simple definition of a gene, but as he, rightly noted: I tell you right now that if I asked a half dozen different biologists to help me out with this, they'd rip into it and add a thousand qualifiers, and it would never get done. Well, okay, technically speaking he didn't ask me for help. But, since I'm a biologist, as soon as I looked at the definition that he chose, from Modern Genetic Analysis (by Griffiths, Lewontin, Miller, and Gelbart), I couldn't help but find something wrong. The definition from…
When we look at a the data for a population+ often the first thing we do is look at the mean. But even if we know that the distribution is perfectly normal, the mean isn't enough to tell us what we know to understand what the mean is telling us about the population. We also need to know something about how the data is spread out around the mean - that is, how wide the bell curve is around the mean. There's a basic measure that tells us that: it's called the standard deviation. The standard deviation describes the spread of the data, and is the basis for how we compute things like the degree…
In general, when we gather data, we expect to see a particular pattern to the data, called a normal distribution. A normal distribution is one where the data is evenly distributed around the mean in a very regular way, which when plotted as a histogram will result in a bell curve. There are a lot of ways of defining "normal distribution" formally, but the simple intuitive idea of it is that in a normal distribution, things tend towards the mean - the closer a value is to the mean, the more you'll see it; and the number of values on either side of the mean at any particular distance are…
Statistics is something that surrounds us every day - we're constantly bombarded with statistics, in the form of polls, tests, ratings, etc. Understanding those statistics can be an important thing, but unfortunately, most people have never been taught just what statistics really mean, how they're computed, or how to distinguish the different between statistics used properly, and statistics misused to deceive. The most basic concept in statistics in the idea of an average. An average is a single number which represents the idea of a typical value. There are three different numbers which can…
The wind storms and heavy rains that hit Seattle recently, demonstrated why a bypass mechanism can be a helpful thing - for both bacteria and motorists. Under the bridge on Mercer, from the Seattle Times When the weather is nice, I bike to work. But when the weather gets bad, (I consider rain and 69 mph winds to be BAD), I take the easy way out. On the day of the big windstorm though, driving home was not so easy. A mudslide covered one of my usual paths, blocked two lanes on a very busy street, and stopped traffic well into the depths of the city. Since we had to get to a soccer…
This is the fifth part of a multipart series on antibiotic resistance in bacteria. The previous installments: 1. A primer on antibiotic resistance: an introduction to the question of antibiotic resistance. 2. Natural vs. synthetic drugs: what is the difference between an antibiotics and synthetic drugs. 3. How do antibiotics kill bacteria? a general discussion of the pathways where antibiotics can act and one characteristic that helps some bacteria survive. 4. Are antibiotics really only made by bacteria and fungi? It depends on what you'd like to call them. Before we go on, I think it's time…
After reading Kevin C.'s question in the comments on my last antibiotic post, I decided to look into this question a bit further. As far as I can tell, most of the commercially producted antibiotics are made by bacteria, fungi, and a bit chemistry (more on that in a moment). It appears, however, that compounds with antimicrobial properties are made by just about everything. Just to make things complicated, these molecules are sometimes called "antibiotics" in the literature and sometimes they're not. Many of the molecules with antimicrobial activity are short peptides- chains of amino…
This is multipart series on antibiotic resistance in bacteria. Check out the previous bits: 1. A primer on antibiotic resistance 2. Natural vs. synthetic drugs Eventually, we'll reach the ways in which bacteria develop antibiotic resistance, but before we get there, we'll spend a little more time on antibiotics themselves. What have we learned so far? 1. Antibiotics are natural products, made by bacteria and some fungi. We have also learned about the difference between antibiotics and synthetic drugs. There isn't always a clear distinction since chemical groups can be added to…
In which I present a quick guide for the omically challenged and a defense of 'arth and "ome." Other SciBloggers have shared their thoughts on the use of ome here and here. Sometimes I get frustrated too, with the way language is abused and tweaked by those around me. So many word pairs that once made phrases—;log in, data set, file name, set up, and pick up—;have been condensed into single words, that I've had to start using Google to double-check my editing. Perhaps it's surprising then, that I like "ome," "omics," and even Sydney Brenner's chief phrase-to-hate, "systems biology." I…
What's the difference between a synthetic drug and an antibiotic? Sometimes there's no difference at all. Let's take a look at chloramphenicol and couple of pencillins. Chloramphenicol kills many different kinds of bacteria by interfering with their ability to make new proteins. Here's a point where language gets tricky. Originally, chloramphenicol was isolated and purified from Streptomyces (a kind of bacteria). But, chloramphenicol is small and chemists are able to synthesize it. So even though we consider antibiotics to be natural products, they don't have to be made in a "natural…
Antibiotics are molecules of biological warfare. Produced by bacteria and some fungi, in response to extracellular signals, antibiotics represent a diverse group of compounds that inhibit bacterial growth at different points and different stages of the life cycle. We will get around to antibiotic resistance, but in these few words, I think I already wrote quite a bit. Admittedly, some of these ideas need a bit of chewing, if they are to be properly digested. Already, I can imagine hands raised and questions waiting to be asked. What are antibiotics made of? I'm confused about this idea…