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epigenetics: fun



The Outbreak Poems — artistic emissions in a pandemic


visualization + design

Creating the Genome Research November 2012 Cover

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Cover image accompanying Spark: A navigational paradigm for genomic data exploration. Genome Research 22 (11). (zoom, Genome Research)

The Genome Research cover design takes a fun and illustrative approach to visualization. It's both art and science — in a 4:1 ratio.

The cover image accompanies the article by Cydney Nielsen from our visualization group, describing her Spark tool for visualization epigenetics data.

Nielsen CB, Younesy H, O'Geen H, Xu X, Jackson AR, et al. (2012) Spark: A navigational paradigm for genomic data exploration. Genome Res 22: 2262-2269.

Instead of a literal depiction of output from Spark, the final design presents what appears to be necklaces of the kind of tiles that Spark uses for its visual presentation. I took a chance that Genome Research had a sense of humor. Luckily, they did and accepted the design for the cover.

Colored tiles are playfully suspended on vertical strings to illustrate how Spark, presented in this issue, uses clustering to group genomic regions (tiles) with similar data patterns (colored heatmaps) and facilitates genome-wide data exploration.Genome Research 22 (11)

The image was published on the November 2012 issue of cover of Genome Research.

Tools

Illustrator CS5, and a cup (or two) of Galileo coffee from a Rancilio Epoca.

Other Covers

I had two other covers published this year: the PNAS cover accompanied our manuscript about mouse vasculature development and the Trends in Genetics cover was commissioned.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Cover image accompanying our article on mouse vasculature development. Biology turns astrophysical. PNAS 1 May 2012; 109 (18) (zoom, how it was made, PNAS)
Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Cover image for the human genetics special issue. Trends in Genetics October 2012, 28 (10) (lowres, hires, how it was made, Trends in Genetics)

source of design

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
To lower this computational barrier, particularly in the early data exploration phases, Spark was developed as an interactive pattern discovery and visualization tool for epigenomic data. (Spark)

Thinking about design ideas for the cover, I looked to the kind of visual motifs that Spark used for inspiration. Immediately the colorful tiles, which represent clustered data tracks, stood out.

Spark's output is very stylized, colorful and high contrast. It was important to preserve this aesthetic in the design. I also wanted to incorporate the idea of clustering in the design, as well as the concept that the clusters represented data from different parts of the genome.

While it was not important to illustrate how Spark organizes and analyzed data explicitly — in fact, I wanted these aspects to be subtle — it was important that the cover illustration had connections to Spark at several levels.

Spark

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Many genomics techniques produce measurements that have both a value and a position on a reference genome, for example ChIP-sequencing.

Spark was created by Cydney Nielsen, who works with me at the Genome Sciences Center. It is designed to mitigate the difficulties arising from the fact that genome-wide data is typically scattered across thousands of points of interest.

Genome browsers integrate diverse data sets by plotting them as vertically stacked tracks across a common genomic x-axis. Genome browsers are designed for viewing local regions of interest (e.g. an individual gene) and are frequently used during the initial data inspection and exploration phases.

Most genome browsers support zooming along the genome coordinate. This type of overview is not always useful because it produces a summary across a continuous genomic range (e.g. chromosome 1) and not across the subset of regions that are of interest (e.g. genes on chromosome 1). Spark addresses this shortcoming and provides a way to help answer questions like: What are the common data patterns across genes start sites in my data set?

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Spark's approach to analysis and display of epigenetic data.

Spark's visualization is driven by clustering data tracks (e.g. ChIP-seq coverage) from across equivalent regions (e.g. gene start sites). The clustered tracks are displayed as heatmaps, with each row being a data track and each column a windowed region of the genome.

early comps

With fond memories of Monte Carlo simulations from my physics days, I set out to simulate some realistic-looking, but entirely synthetic, Spark cluster tiles.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
A collection of synthetic Spark tiles, each 7x20.

My first idea was a design which would show these tiles falling, perhaps accumulating on a pile on the ground. Quick prototypes of this idea were disappointing. The tiles appeared flimsy and too complex, while the image was largely empty. I spent several hours messing around with the rotation and pseudo-3D layout, but could not find anything that was satisfying.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Spark tiles, falling.
Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Early attempt at a design. Meh.

I thought to do this right would require a proper simulation within a 3D system.

refining the design

To address the fact that the tiles felt flimsy and overly complicated and the design lacked depth, I simplified the tile simulation to generate 5x5 tiles. These simpler representations still embodied how Spark displayed data, but did so minimally.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
A second attempt at simulating Spark clusters.

To keep with the idea that the clusters come from different regions of the genome, I thought of arranging them along line segments. Unlike the design in which the tiles were falling, this constrained the layout significantly and allowed me to play with the design to make it look like the clusters were draped over it. By casting a light shadow behind each string of tiles, a subtle 3D effect could be achieved while still keeping the design within a plane.

There are 11 orientations of tiles created by rotating a thin square around the vertical axis with a slight forward tilt. There are 5 rotations to the left and right at angles 10, 26, 46, 66 and 80 degrees. The rotation was achieved using Illustrator's Extrude and Bevel 3D filter.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Layout of tiles.
Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Rotated tiles with Spark clusters.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Flight and Fall by Rachel Nottingham. (artist's site)

The layout and rotation of the tiles was inspired by Flight and Fall by Rachel Nottingham, a mobile of paper birds.

I wanted to keep the layout of the spark tiles pleasant, without being too organized. I find this to be a difficult balance to achieve — natural randomness is deceptively difficult to create by hand.

final image

Four different versions of the design were submitted to Genome Research. I was happiest with the treatment in which the tiles maintained their color and the Spark clusters were projected as tones of white. This designed felt more solid and punchy — I feel like you can reach out and touch one of those strings.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Final Spark cover designs. The top left one was chosen by Genome Research.

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news + thoughts

Points of Significance celebrates 50th column

Mon 24-08-2020

We are celebrating the publication of our 50th column!

To all our coauthors — thank you and see you in the next column!

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance: Celebrating 50 columns of clear explanations of statistics. (read)

Uncertainty and the management of epidemics

Mon 24-08-2020

When modelling epidemics, some uncertainties matter more than others.

Public health policy is always hampered by uncertainty. During a novel outbreak, nearly everything will be uncertain: the mode of transmission, the duration and population variability of latency, infection and protective immunity and, critically, whether the outbreak will fade out or turn into a major epidemic.

The uncertainty may be structural (which model?), parametric (what is `R_0`?), and/or operational (how well do masks work?).

This month, we continue our exploration of epidemiological models and look at how uncertainty affects forecasts of disease dynamics and optimization of intervention strategies.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Uncertainty and the management of epidemics. (read)

We show how the impact of the uncertainty on any choice in strategy can be expressed using the Expected Value of Perfect Information (EVPI), which is the potential improvement in outcomes that could be obtained if the uncertainty is resolved before making a decision on the intervention strategy. In other words, by how much could we potentially increase effectiveness of our choice (e.g. lowering total disease burden) if we knew which model best reflects reality?

This column has an interactive supplemental component (download code) that allows you to explore the impact of uncertainty in `R_0` and immunity duration on timing and size of epidemic waves and the total burden of the outbreak and calculate EVPI for various outbreak models and scenarios.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Uncertainty and the management of epidemics. (Interactive supplemental materials)

Bjørnstad, O.N., Shea, K., Krzywinski, M. & Altman, N. (2020) Points of significance: Uncertainty and the management of epidemics. Nature Methods 17.

Background reading

Bjørnstad, O.N., Shea, K., Krzywinski, M. & Altman, N. (2020) Points of significance: Modeling infectious epidemics. Nature Methods 17:455–456.

Bjørnstad, O.N., Shea, K., Krzywinski, M. & Altman, N. (2020) Points of significance: The SEIRS model for infectious disease dynamics. Nature Methods 17:557–558.

Cover of Nature Genetics August 2020

Mon 03-08-2020

Our design on the cover of Nature Genetics's August 2020 issue is “Dichotomy of Chromatin in Color” . Thanks to Dr. Andy Mungall for suggesting this terrific title.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Dichotomy of Chromatin in Color. Nature Genetics, August 2020 issue. (read more)

The cover design accompanies our report in the issue Gagliardi, A., Porter, V.L., Zong, Z. et al. (2020) Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade–specific epigenome and transcriptome landscapes. Nature Genetics 52:800–810.

Poster Design Guidelines

Wed 15-07-2020

Clear, concise, legible and compelling.

The PDF template is a poster about making posters. It provides design, typography and data visualiation tips with minimum fuss. Follow its advice until you have developed enough design sobriety and experience to know when to go your own way.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Poster Design Guidelines — Clear, concise, legible and compelling..

The SEIRS model for infectious disease dynamics

Thu 18-06-2020

Realistic models of epidemics account for latency, loss of immunity, births and deaths.

We continue with our discussion about epidemic models and show how births, deaths and loss of immunity can create epidemic waves—a periodic fluctuation in the fraction of population that is infected.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: The SEIRS model for infectious disease dynamics. (read)

This column has an interactive supplemental component (download code) that allows you to explore epidemic waves and introduces the idea of the phase plane, a compact way to understand the evolution of an epidemic over its entire course.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: The SEIRS model for infectious disease dynamics. (Interactive supplemental materials)

Bjørnstad, O.N., Shea, K., Krzywinski, M. & Altman, N. (2020) Points of significance: The SEIRS model for infectious disease dynamics. Nature Methods 17:557–558.

Background reading

Bjørnstad, O.N., Shea, K., Krzywinski, M. & Altman, N. (2020) Points of significance: Modeling infectious epidemics. Nature Methods 17:455–456.