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Canada's Michael Smith Genome Sciences Centre (GSC) at PHSA is an international leader in genomics, proteomics and bioinformatics for precision medicine. By developing and deploying cutting-edge genome sequencing, computational and analytical technology, we are creating novel strategies to prevent and diagnose cancers and other diseases, uncovering new therapeutic targets and helping the world realize the social and economic benefits of genome science.
We are the Canadian node of the Earth Biogenome Project.

Art of the Personalized Oncogenomics Program

A poet is, after all, a sort of scientist, but engaged in a qualitative science in which nothing is measurable. He lives with data that cannot be numbered, and his experiments can be done only once. The information in a poem is, by definition, not reproducible. He becomes an equivalent of scientist, in the act of examining and sorting the things popping in [to his head], finding the marks of remote similarity, points of distant relationship, tiny irregularities that indicate that this one is really the same as that one over there only more important. Gauging the fit, he can meticulously place pieces of the universe together, in geometric configurations that are as beautiful and balanced as crystals.
— Lewis Thomas (The Medusa and the Snail: More Notes of a Biology Watcher)

1 · What do the circles mean?

The legend can be printed at 4" × 6". The bitmap resolution is 600 dpi.


 / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Quick legend. 5 Years of Personalized Oncogenomics Project at Canada's Michael Smith Genome Sciences Centre. The poster shows 545 cancer cases.

2 · A case for a visual case summary

For every case, we sequence the DNA to study the genome structure and the RNA to discover which genes are expressed and to what extent. The analysis is quite complex and brings together many steps: sequence alignment, structural variation detection, expression profiling, pathway analysis and so on. Every case is "summarized" by a lengthy report, such as the one below, which can run to over 40 pages.

Personalized Oncogenomics Program at Canada's Michael Smith Genome Sciences Center / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
A report for a typical POG case is about 40–50 pages.

One of the goals of the 5-year anniversary art was to represent the cases in a way to clearly show their number, classification as well as diversity. There are many metrics that can be used and I decided to choose the case's correlation to other cancer types.

correlation to TCGA cancer database

For every POG case, the gene expression of 1,744 key genes is compared to that of 1,000's of cases in the TCGA database of cancer samples. For a given cancer type in the TCGA database (e.g. BRCA), we visualize the correlations using box plots. The box plot is ideal for showing the distribution of values in a sample.

Personalized Oncogenomics Program at Canada's Michael Smith Genome Sciences Center / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Every case is compared to a database of 1,000's of cases. Shown here are box plots for the Spearman correlation coefficient between the gene expression of the POG case and cancers of a specific type (e.g. BRCA, LUAD, etc).

The 10 largest Spearman correlation coefficients for the case shown above are

case    corr    type     tissue
-----------------------------------------------
POG661	0.436	BRCA	 Breast
POG661	0.371	PRAD	 Urologic
POG661	0.295	OV	 Gynecologic
POG661	0.257	UCEC	 Gynecologic
POG661	0.244	LUAD	 Thoracic
POG661	0.235	CESC_CAD Gynecologic
POG661	0.225	MB_Adult Central Nervous System
POG661	0.222	KICH	 Urologic
POG661	0.219	THCA	 Endocrine
POG661	0.208	UCS	 Gynecologic

In the figure below I show how the final encoding of the correlations is done. First, the top three correlations are taken—using more generates a busy look and diminishes visual impact. The correlations are encoded as concentric rings.

Because in most cases the differences in the top 3 correlations are relatively small, differences are emphasized by non-linearly scaling the encoding (the correlations are first scaled `r^3`).

Personalized Oncogenomics Program at Canada's Michael Smith Genome Sciences Center / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Case POG661. Median gene expression correlations with different cancer types from TCGA database. (A) Top 10 correlations shown as a bar plot. Color coding is by source tissue associated with the cancer type. (B) Top 10 correlations encoded as concentric rings. The width of the ring is proportional to the correlation. (C) Top 3 correlations. (D) Top 3 correlations scaled with a power to emphasize differences.

The type face is Proxima Nova. The colors for each tissue source are

         Gastrointestinal  234,62,144
                   Breast  237,75,51
                 Thoracic  242,130,56
              Gynecologic  253,188,61
              Soft tissue  244,217,59
                     Skin  193,216,51
                 Urologic  114,197,49
              Hematologic  29,166,68
            Head and neck  43,168,224
                Endocrine  71,82,178
   Central nervous system  127,65,146
                    Other  150,150,150
news + thoughts

Propensity score weighting

Mon 04-05-2026

It is not certain that everything is uncertain. —Blaise Pascal

We have already explored how we can mitigate bias caused by confounding variables in observational studies using propensity score (PS) matching (PSM) and propensity score weighting (PSW). However, any statistical model is only as good as its assumptions and, if it is specified incorrectly, it can itself produce biased estimates of the treatment effect.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Double Robustness. (read)

This month, we explore double robustness, a powerful statistical concept that provides a valuable “safety net” against the risk of an incorrect model. It offers two opportunities, instead of just one, to obtain a valid estimate of the treatment effect — making it possible to draw credible causal inferences from observational data without having to depend on a single set of modeling assumptions.

Kurz, C.F., Krzywinski, M. & Altman, N. (2026) Points of significance: Double Robustness. Nat. Methods 23:868–869.

Nature Biotechnology cover

Thu 23-04-2026

My cover design on the 7 April 2026 Nature Biotechnology issue shows the dendrogram that represents a cluster of uniquely expressed (or downregulated) genes in human naive stem cells induced from such cells. Within each dendrogram block, the genomic barcode sequence (sampled from Supplementary Table 1) is depicted with a Code 39 barcode. The highlighted barcode is one of those used for cell isolation.

Ishiguro S. et al. A multi-kingdom genetic barcoding system for precise clone isolation (2026) Nature Biotechnology 44:616–629.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
My Nature Biotechnology phylogenetic tree cover (volume 44, issue 4, 7 April 2026). (more)

Browse my gallery of cover designs.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
A catalogue of my journal and magazine cover designs. (more)

Happy 2026 π Day—
Art for the 5%

Fri 13-03-2026

Celebrate π Day (March 14th) and enjoy the art — but only if you're part of the 5%.

Go ahead, see what you can't see.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
2026 π DAY | Art for the 5%. Shown in the style of Ishihara color test plates, the art is visible only to those with colour blindness. (details)

Ishihara's Tests for Colour Deficiency

Sun 08-03-2026

Authentic and accurate images of Ishihara's test plates photographed (and lovingly color-corrected) from the 38-plate Ishihara's Tests for Colour Deficiency.

I also provide the position, size, and color of each circle on each test plate.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
ISHIHARA'S TEST PLATE 6 | This plate is part of the set of transformation plates. If you see 5, you're ok. If you see 2, you're not. (details)
Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
ISHIHARA'S TEST PLATE 18 | This plate is part of the set of mysterious hidden plates. If you don't see anything, you're ok. If you see 5, you're not. (details)

Symmetric alternatives to the ordinary least squares regression

Wed 23-07-2025

What immortal hand or eye, could frame thy fearful symmetry? — William Blake, "The Tyger"

This month, we look at symmetric regression, which, unlike simple linear regression, it is reversible — remaining unaltered when the variables are swapped.

Simple linear regression can summarize the linear relationship between two variables `X` and `Y` — for example, when `Y` is considered the response (dependent) and `X` the predictor (independent) variable.

However, there are times when we are not interested (or able) to distinguish between dependent and independent variables — either because they have the same importance or the same role. This is where symmetric regression can help.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Symmetric alternatives to the ordinary least squares regression. Geometry of quantities minimized in OLS and symmetric regression. OLS minimizes `\Sigma e_y^2` in `Y` ~ `X` and `\Sigma e_x^2` `X` ~ `Y`. Pythagorean regression minimizes AB (magenta). Geometric means regression (GMR) minimizes area of ABP (orange). Orthogonal regression (OR) minimizes HP (blue). (read)

Luca Greco, George Luta, Martin Krzywinski & Naomi Altman (2025) Points of significance: Symmetric alternatives to the ordinary least squares regression. Nat. Methods 22:1610–1612.

Beyond Belief Campaign BRCA Art

Wed 11-06-2025

Fuelled by philanthropy, findings into the workings of BRCA1 and BRCA2 genes have led to groundbreaking research and lifesaving innovations to care for families facing cancer.

This set of 100 one-of-a-kind prints explore the structure of these genes. Each artwork is unique — if you put them all together, you get the full sequence of the BRCA1 and BRCA2 proteins.

Martin Krzywinski | contact | Canada's Michael Smith Genome Sciences CentrePHSA
Google whack “vicissitudinal corporealization”
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