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Where am I supposed to go? Where was I supposed to know?Violet Indianaget lost in questionsmore quotes

microscopy: small


In Silico Flurries: Computing a world of snow. Scientific American. 23 December 2017


data visualization + art

Creating the Molecular Case Studies Cover

If your photos aren’t good enough, then you’re not close enough
— Robert Capa

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Cover design for Apr 2018 issue of Molecular Case Studies. (zoom)

about the cover

Papillary thyroid carcinoma (PTC) cells, even though malignant, are still genetically programmed to try to be thyroid follicles and may retain their follicular growth pattern, which appear as circles on cross section. Two diagnostic features of papillary thyroid carcinoma are nuclear clearing and intranuclear cytoplasmic inclusions. The black-and-white image is an artistic treatment of a PTC microscopy image (40×) from one of the Personalized Oncogenomics Program study participants at the BC Cancer Research Center. Superimposed is a Circos plot of 17 genomic fusions involving 17 chromosomes identified in the sample by whole-genome sequencing. Showing through the Circos plot is an enhanced color version of the microscopy image. The original image is from Application of genomics to identify therapeutic targets in recurrent pediatric papillary thyroid carcinoma by Ronsley et al. in the April 2018 issue.


The theme of the April issue of Molecular Case Studies is precision oncogenomics. We have three papers in the issue based on work done in our Personalized Oncogenomics Program (POG).

...this special issue provide[s] a glimpse into current cancer precision medicine efforts, reflecting only a microcosm of ... genomics in this bustling space of clinical translation.
John C. Carpten & Elaine R. Mardis
The era of precision oncogenomics
Mol. Case Stud. (2018) 4(2).

I've previously created art based on POG data—posters to celebrate the program's 5-year anniversary.

input materials

The covers of Molecular Case Studies typically show microscopy images, with some shown in a more abstract fashion. There's also the occasional Circos plot.

I've previously taken a more fine-art approach to cover design, such for those of Nature, Genome Research and Trends in Genetics. I've used microscopy images to create a cover for PNAS—the one that made biology look like astrophysics—and thought that this is kind of material I'd start with for the MCS cover.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
A few of the microscopy slides submitted to me for the cover design. Courtesy of Anna Lee (Dept Pathology and Laboratory Medicine, UBC).

When I look at these kind of images, I have basically no idea what I'm looking at. Sure, I know this is life at tiny scale but I am not a pathologist. This helps me greatly.

Instead, I see color, shapes, and contrast. I hunt for patterns that would make for an interesting visual, without necessarily trying to communicate any of the science behind that—the paper does a much better job at this than I ever could. It's largely a process driven by intuition and my desire to see distinct visual patterns at different length scales with some symmetry, ideally broken in a pleasing way. Vague, I know.

Images of different regions of the same slide, at the same magnification, can have very different levels of visual engagement (for the non-specialist). Just compare the two images below.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Same magnification, same slide. The image on the right is interesting. The one on the left is not, artistically speaking. Courtesy of Anna Lee (Dept Pathology and Laboratory Medicine, UBC).

The slide on the left really caught my eye. It had the right proportion of tiny, small, medium and large things.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
I see a heart, a face and lava flow among faces. Obviously, faces everywhere—humans are good at those kinds of Type I errors. The panels below are 100% crops of the 40× slide of papillary thyroid carcinoma shown above them. Courtesy of Anna Lee (Dept Pathology and Laboratory Medicine, UBC).

black and white version

The black-and-white version was obtained by solarizing the image. There are both color and black-and-white options for solarization, a method in which various tones of the image are remapped in brightness.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
(A) The original slide (B) A black-and-white composition using Nik Color Efex 4 filters applied in succession to the slide: dark contrast, tonal contrast, white neutralizer and solarization.
Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Compounding effects of each of the filters on the image above.

And here's the first black-and-white take.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The initial black-and-white composition after applying Nik filters.

This looked good but a bit dark. I handled this by lightening the tone, differently depending on the element in the image. I also wanted to bring out more details in the internal structure of the cells. This was achieved by applying an otherwise aggressive sharpening mask.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The effect of additional sharpening and tone remaps, applied differently to intracellular and extracellular regions.

I was quite happy with this result. The combination of solarization and sharpening created a large variety of patterns inside the cells. My brain fought hard to see faces in them.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
100% crops of regions of the above black-and-white image. I see a heart (this is the same heart region shown in the color crop above), then a some kind of dog/cat chimera, in the last panel, a suprrised or scared camel. If you look very carefully, you can see a grumpy cat coming out of the heart.

Because I had slides at different magnifications, I created a design in which three slides at 10, 20 and 40 × were composited together so that from left to right the magnification increased across the image. The effect is subtle—you can easily miss it, which is the point.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
A seamless stitch of black-and-white treatments of 10, 20 and 40 × slides. As you go from left to right, the magnification increases.

I had pretty high hopes for these black-and-white versions. Previous covers in MCS have been colorful, though, so I thought to provide a color option.

color version

For the color version, I wanted to give the colors more punch. For sure.

I also wanted to emphasize the details, like for the black-and-white image.

The first process step of the color slide was done using 5 Nik filters, applied in succession: dark contrast, tonal contrast, sunlight, polarization and detail extractor. The effects of the stack of these filters is shown on the original image below. The whole image is shown and in each strip the filters are stacked.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The effect of stacking 5 Nik filters on the original image.

Here's the full image with the 5 Nik filters applied.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
A seamless stitch of black-and-white treatments of 10, 20 and 40 × slides. As you go from left to right, the magnification increases.

Not there yet, though. I added more sharpening (more than I've ever used before, so I felt a little weird, but got over it quickly). The colors were punched up too—I wanted more contrast between the blue and red areas and transform the reds a little into oranges.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
A seamless stitch of black-and-white treatments of 10, 20 and 40 × slides. As you go from left to right, the magnification increases.

If it looks like the blue areas are popping out of the image, that's the effect of the emboss filter.

final composition

The editors asked me to encorporate a Circos image in the final design. This was tricky—I had spent a lot of time up to now fiddling with extracting patterns and textures from the images.

Something as geometrical and rational as a data graphic would alter the personality of the design. But, the goal of artistic collaboration is always to find a way, so I took some gene fusions that were found in the sample with our structural variant pipeline and created a bare-bones Circos image out of them.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
A seamless stitch of black-and-white treatments of 10, 20 and 40 × slides. As you go from left to right, the magnification increases.

This was then superimposed on the image and emphasized by using the color design inside the circle and black-and-white design outside.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The final composition for the cover combines both black-and-white and color treatments. The colored pattern stands out above the black-and-white background.

It's always fun to invert images and see what happens.

Molecualar Case Studies - Creating the April 2018 cover / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Inverse of the above. Notice how the pattern inside the circle appears to be sitting below the plane, making the circle more of a window to a scene. .
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news + thoughts

Optimal experimental design

Tue 31-07-2018
Customize the experiment for the setting instead of adjusting the setting to fit a classical design.

The presence of constraints in experiments, such as sample size restrictions, awkward blocking or disallowed treatment combinations may make using classical designs very difficult or impossible.

Optimal design is a powerful, general purpose alternative for high quality, statistically grounded designs under nonstandard conditions.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Optimal experimental design. (read)

We discuss two types of optimal designs (D-optimal and I-optimal) and show how it can be applied to a scenario with sample size and blocking constraints.

Smucker, B., Krzywinski, M. & Altman, N. (2018) Points of significance: Optimal experimental design Nature Methods 15:599–600.

Background reading

Krzywinski, M., Altman, N. (2014) Points of significance: Two factor designs. Nature Methods 11:1187–1188.

Krzywinski, M. & Altman, N. (2014) Points of significance: Analysis of variance (ANOVA) and blocking. Nature Methods 11:699–700.

Krzywinski, M. & Altman, N. (2014) Points of significance: Designing comparative experiments. Nature Methods 11:597–598.

The Whole Earth Cataloguer

Mon 30-07-2018
All the living things.

An illustration of the Tree of Life, showing some of the key branches.

The tree is drawn as a DNA double helix, with bases colored to encode ribosomal RNA genes from various organisms on the tree.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The circle of life. (read, zoom)

All living things on earth descended from a single organism called LUCA (last universal common ancestor) and inherited LUCA’s genetic code for basic biological functions, such as translating DNA and creating proteins. Constant genetic mutations shuffled and altered this inheritance and added new genetic material—a process that created the diversity of life we see today. The “tree of life” organizes all organisms based on the extent of shuffling and alteration between them. The full tree has millions of branches and every living organism has its own place at one of the leaves in the tree. The simplified tree shown here depicts all three kingdoms of life: bacteria, archaebacteria and eukaryota. For some organisms a grey bar shows when they first appeared in the tree in millions of years (Ma). The double helix winding around the tree encodes highly conserved ribosomal RNA genes from various organisms.

Johnson, H.L. (2018) The Whole Earth Cataloguer, Sactown, Jun/Jul, p. 89

Why we can't give up this odd way of typing

Mon 30-07-2018
All fingers report to home row.

An article about keyboard layouts and the history and persistence of QWERTY.

My Carpalx keyboard optimization software is mentioned along with my World's Most Difficult Layout: TNWMLC. True typing hell.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
TNWMLC requires seriously flexible digits. It’s 87% more difficult than using a standard Qwerty keyboard, according to Martin Krzywinski, who created it (Credit: Ben Nelms). (read)

McDonald, T. (2018) Why we can't give up this odd way of typing, BBC, 25 May 2018.

Molecular Case Studies Cover

Fri 06-07-2018

The theme of the April issue of Molecular Case Studies is precision oncogenomics. We have three papers in the issue based on work done in our Personalized Oncogenomics Program (POG).

The covers of Molecular Case Studies typically show microscopy images, with some shown in a more abstract fashion. There's also the occasional Circos plot.

I've previously taken a more fine-art approach to cover design, such for those of Nature, Genome Research and Trends in Genetics. I've used microscopy images to create a cover for PNAS—the one that made biology look like astrophysics—and thought that this is kind of material I'd start with for the MCS cover.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Cover design for Apr 2018 issue of Molecular Case Studies. (details)

Happy 2018 `\tau` Day—Art for everyone

Wed 27-06-2018
Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
You know what day it is. (details)

Universe Superclusters and Voids

Mon 25-06-2018

A map of the nearby superclusters and voids in the Unvierse.

By "nearby" I mean within 6,000 million light-years.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The Universe — Superclustesr and Voids. The two supergalactic hemispheres showing Abell clusters, superclusters and voids within a distance of 6,000 million light-years from the Milky Way. (details)