Here we are now at the middle of the fourth large part of this talk.
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Lately, I've been making a lot of square things round. So when Rhiannon Macrae, the Editor of Trends in Genetics, requested a Circos-like cover image for the human genetics special edition of the journal, I started drawing circles.

The image was published on the cover of Trends in Genetics human genetics special issue (Trends in Genetics October 2012, 28 (10)).

Circos has appeared on covers of journals and books. Some of the images were designed by me and others were drawn from papers published in the issue.

I have a collection of unpublished Circos posters and thought these might be a good starting point. Rhiannon and I narrowed the choice down to the black-and-white design that showed sequenced organisms. We also liked the complex style of a panel of hundreds of Circos images generated with the tableviewer.

The idea would be that the foreground would be more artistic and stylized, while the background was more technical and complex. I have thousands of images available from the tableviewer (e.g. huge 15,129 image matrix).

Rhiannon also wanted to include the quote by Henry David Thoreau, *"Nature and human life are as various as our several constitutions. Who shall say what prospect life offers to another?"* This reminded me of a similar but more tragic line from Shakespeare's Julius Caesar, *"How many ages hence shall this our lofty scene be acted over in states unborn and accents yet unknown!"*

In the early comps we played around with the idea of using non-genomics elements in the image, such as coins. We thought that we could use the variety of color and shape of the coins to communicate the idea of genetic diversity. However, after wrestling with how to do this effectively the concept was scrapped — the idea of using coins felt both arcane and arbitrary.

I decided to go with a warm brown color scheme. It's not a color I use a lot of, which makes me think that I *should* try to do more with it.

Deep brown provides great contrast for saturated colors, though I had to be careful not to make the image look too kitchy with an excess of colour variation. In some of the early comps shown above, two or more different color palettes were used (e.g. grey/red/blue and false color) and this lowered to overall visual cohesion of the image.

It's always a good idea to add variety to design. After all, without *any variety* we'd be left with a blank page. Ok, so variety *is* good, but too much variety is very bad, and can make you wish for that blank page again. Think about this: one kind of variety already provides variety! A variety of variety (I run the risk of recursing myself *ad infinitum*) can not only compete for attention but resonate destructively (that's design-speak for "turn into visual mush").

Everyone liked the combination of bright colors and dark background. This is an approach I favour too, which has worked well on other covers.

Briefly I experimented with various brush and pencil filters to give the image a more hand-drawn and organic look. Most of the illustrations I generate are very digital — blocks of solid colors and high-contrast shapes — and I thought a departure from this look could work in this case. However, like with the coins, this path didn't produce anything productive.

Building on last month's column about Bayes' Theorem, we introduce Bayesian inference and contrast it to frequentist inference.

Given a hypothesis and a model, the frequentist calculates the probability of different data generated by the model, *P*(data|model). When this probability to obtain the observed data from the model is small (e.g. `alpha` = 0.05), the frequentist rejects the hypothesis.

In contrast, the Bayesian makes direct probability statements about the model by calculating P(model|data). In other words, given the observed data, the probability that the model is correct. With this approach it is possible to relate the probability of different models to identify one that is most compatible with the data.

The Bayesian approach is actually more intuitive. From the frequentist point of view, the probability used to assess the veracity of a hypothesis, P(data|model), commonly referred to as the *P* value, does not help us determine the probability that the model is correct. In fact, the *P* value is commonly misinterpreted as the probability that the hypothesis is right. This is the so-called "prosecutor's fallacy", which confuses the two conditional probabilities *P*(data|model) for *P*(model|data). It is the latter quantity that is more directly useful and calculated by the Bayesian.

Puga, J.L, Krzywinski, M. & Altman, N. (2015) Points of Significance: Bayes' Theorem *Nature Methods* **12**:277-278.

Puga, J.L, Krzywinski, M. & Altman, N. (2015) Points of Significance: Bayes' Theorem *Nature Methods* **12**:277-278.

In our first column on Bayesian statistics, we introduce conditional probabilities and Bayes' theorem

*P*(B|A) = *P*(A|B) × *P*(B) / *P*(A)

This relationship between conditional probabilities *P*(B|A) and *P*(A|B) is central in Bayesian statistics. We illustrate how Bayes' theorem can be used to quickly calculate useful probabilities that are more difficult to conceptualize within a frequentist framework.

Using Bayes' theorem, we can incorporate our beliefs and prior experience about a system and update it when data are collected.

Puga, J.L, Krzywinski, M. & Altman, N. (2015) Points of Significance: Bayes' Theorem *Nature Methods* **12**:277-278.

Oldford, R.W. & Cherry, W.H. Picturing probability: the poverty of Venn diagrams, the richness of eikosograms. (University of Waterloo, 2006)

Celebrate `pi` Day (March 14th) with splitting its digit endlessly. This year I use a treemap approach to encode the digits in the style of Piet Mondrian.

The art has been featured in Ana Swanson's Wonkblog article at the Washington Post—10 Stunning Images Show The Beauty Hidden in `pi`.

I also have art from 2013 `pi` Day and 2014 `pi` Day.

The split plot design originated in agriculture, where applying some factors on a small scale is more difficult than others. For example, it's harder to cost-effectively irrigate a small piece of land than a large one. These differences are also present in biological experiments. For example, temperature and housing conditions are easier to vary for groups of animals than for individuals.

The split plot design is an expansion on the concept of blocking—all split plot designs include at least one randomized complete block design. The split plot design is also useful for cases where one wants to increase the sensitivity in one factor (sub-plot) more than another (whole plot).

Altman, N. & Krzywinski, M. (2015) Points of Significance: Split Plot Design *Nature Methods* **12**:165-166.

1. Krzywinski, M. & Altman, N. (2014) Points of Significance: Designing Comparative Experiments *Nature Methods* **11**:597-598.

2. Krzywinski, M. & Altman, N. (2014) Points of Significance: Analysis of variance (ANOVA) and blocking *Nature Methods* **11**:699-700.

3. Blainey, P., Krzywinski, M. & Altman, N. (2014) Points of Significance: Replication *Nature Methods* **11**:879-880.

In an audience of 8 men and 8 women, chances are 50% that at least one has some degree of color blindness^{1}. When encoding information or designing content, use colors that is color-blind safe.