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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

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.

Propensity score weighting

Mon 17-03-2025

The needs of the many outweigh the needs of the few. —Mr. Spock (Star Trek II)

This month, we explore a related and powerful technique to address bias: propensity score weighting (PSW), which applies weights to each subject instead of matching (or discarding) them.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Propensity score weighting. (read)

Kurz, C.F., Krzywinski, M. & Altman, N. (2025) Points of significance: Propensity score weighting. Nat. Methods 22:1–3.

Happy 2025 π Day—
TTCAGT: a sequence of digits

Thu 13-03-2025

Celebrate π Day (March 14th) and sequence digits like its 1999. Let's call some peaks.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
2025 π DAY | TTCAGT: a sequence of digits. The digits of π are encoded into DNA sequence and visualized with Sanger sequencing. (details)

Crafting 10 Years of Statistics Explanations: Points of Significance

Sun 09-03-2025

I don’t have good luck in the match points. —Rafael Nadal, Spanish tennis player

Points of Significance is an ongoing series of short articles about statistics in Nature Methods that started in 2013. Its aim is to provide clear explanations of essential concepts in statistics for a nonspecialist audience. The articles favor heuristic explanations and make extensive use of simulated examples and graphical explanations, while maintaining mathematical rigor.

Topics range from basic, but often misunderstood, such as uncertainty and P-values, to relatively advanced, but often neglected, such as the error-in-variables problem and the curse of dimensionality. More recent articles have focused on timely topics such as modeling of epidemics, machine learning, and neural networks.

In this article, we discuss the evolution of topics and details behind some of the story arcs, our approach to crafting statistical explanations and narratives, and our use of figures and numerical simulations as props for building understanding.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Crafting 10 Years of Statistics Explanations: Points of Significance. (read)

Altman, N. & Krzywinski, M. (2025) Crafting 10 Years of Statistics Explanations: Points of Significance. Annual Review of Statistics and Its Application 12:69–87.

Propensity score matching

Mon 16-09-2024

I don’t have good luck in the match points. —Rafael Nadal, Spanish tennis player

In many experimental designs, we need to keep in mind the possibility of confounding variables, which may give rise to bias in the estimate of the treatment effect.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Propensity score matching. (read)

If the control and experimental groups aren't matched (or, roughly, similar enough), this bias can arise.

Sometimes this can be dealt with by randomizing, which on average can balance this effect out. When randomization is not possible, propensity score matching is an excellent strategy to match control and experimental groups.

Kurz, C.F., Krzywinski, M. & Altman, N. (2024) Points of significance: Propensity score matching. Nat. Methods 21:1770–1772.

Understanding p-values and significance

Tue 24-09-2024

P-values combined with estimates of effect size are used to assess the importance of experimental results. However, their interpretation can be invalidated by selection bias when testing multiple hypotheses, fitting multiple models or even informally selecting results that seem interesting after observing the data.

We offer an introduction to principled uses of p-values (targeted at the non-specialist) and identify questionable practices to be avoided.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Understanding p-values and significance. (read)

Altman, N. & Krzywinski, M. (2024) Understanding p-values and significance. Laboratory Animals 58:443–446.

Martin Krzywinski | contact | Canada's Michael Smith Genome Sciences CentrePHSA
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