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Canada's Michael Smith Genome Sciences Centre (GSC) at BC Cancer 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)


 / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
5 Years of Personalized Oncogenomics Project at Canada's Michael Smith Genome Sciences Centre. The poster shows 545 cancer cases. Cases ordered chronologically by case number.

 / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
5 Years of Personalized Oncogenomics Project at Canada's Michael Smith Genome Sciences Centre. The poster shows 545 cancer cases. Cases grouped by diagnosis (tissue type) and then by similarity within group.

1 · Cancer is the difference of differences

As individuals, we all have slightly different genomes. If you compare the genomes of two people, you will find about 3 million base pair differences, which is about 0.1% of the genome.

This variation exists not only within the population but potentially also, to a lesser extent, among our cells, which number around 40 trillion. That's roughly 10,000 cells for each base in your 3 billion base genome. And each has a role to play.

POG cases, by tissue type
n %
Gastrointestinal 141 25
 
Breast 138 25
 
Thoracic 57 10
 
Gynecologic 45 8.3
 
Soft tissue 44 8.1
 
Skin 11 2.0
 
Urologic 8 1.5
 
Hematologic 7 1.3
 
Head and neck 6 1.1
 
Endocrine 5 0.9
 
Central nervous system 5 0.9
 
Other 78 14
 
ALL 545

One consequence of this complexity and variation is that changes in the genome (through mutation or other processes) can have very different effects, depending on both the change and the genome. Cancer is a phenomena in which cells' ability to organize themselves as they divide is altered due to changes in the genome. It is an incredibly complex biological phenomenon—considering all the genomes in the population and all the possible changes that may arise, there is truly an inexhaustible number of ways in which the genome can break.

2 · Classifying cancer

Cancers are classified according to their site of origin, such as lung, breast, liver, or colon. This is a coarse grouping—within each group there are many subtypes with differences in response to treatment and overall behaviour.

3 · Diversities among clinical cases

The design of the POG art highlights the diversity and similarity among cases. The diversity is what makes the study of cancer difficult and the similarities are what makes inference possible.

Personalized Oncogenomics Program at Canada's Michael Smith Genome Sciences Center / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca

Each case is represented by three concentric rings. The width of each ring represents the extent to which the case is similar (as measured by correlation) to cancers of the type encoded by the color of the ring (see Methods).

4 · Remixes

In additional to the posters, I've created remixes for your desktop at 4k resolution.


 / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
png
5 Years of Personalized Oncogenomics Project at Canada's Michael Smith Genome Sciences Centre. The poster shows 545 cancer cases. Cases ordered chronologically by case number.

 / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
png
5 Years of Personalized Oncogenomics Project at Canada's Michael Smith Genome Sciences Centre. The poster shows 545 cancer cases. Cases ordered chronologically by case number.

 / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
png
5 Years of Personalized Oncogenomics Project at Canada's Michael Smith Genome Sciences Centre. The poster shows 545 cancer cases. Cases ordered chronologically by case number.

 / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
png
5 Years of Personalized Oncogenomics Project at Canada's Michael Smith Genome Sciences Centre. The poster shows 545 cancer cases. Cases ordered chronologically by case number.

5 · Ride to Conquer Cancer — Data-powered, human-driven

This year, the cyclists in the Ride to Conquer Cancer will not only have the chance to raise money for research (as they've always done) but also do so while wearing data (as they've never done before).

Personalized Oncogenomics Program at Canada's Michael Smith Genome Sciences Center / Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The design on the posters is being used for the Vancouver Ride to Conquer Cancer cycling jersey. (buy a jersey, tour info)

You can purchase your own data-powered and human-driven cycling jersey.

news + thoughts

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.

Nasa to send our human genome discs to the Moon

Sat 23-03-2024

We'd like to say a ‘cosmic hello’: mathematics, culture, palaeontology, art and science, and ... human genomes.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
SANCTUARY PROJECT | A cosmic hello of art, science, and genomes. (details)
Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
SANCTUARY PROJECT | Benoit Faiveley, founder of the Sanctuary project gives the Sanctuary disc a visual check at CEA LeQ Grenoble (image: Vincent Thomas). (details)
Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
SANCTUARY PROJECT | Sanctuary team examines the Life disc at INRIA Paris Saclay (image: Benedict Redgrove) (details)

Comparing classifier performance with baselines

Fri 22-03-2024

All animals are equal, but some animals are more equal than others. —George Orwell

This month, we will illustrate the importance of establishing a baseline performance level.

Baselines are typically generated independently for each dataset using very simple models. Their role is to set the minimum level of acceptable performance and help with comparing relative improvements in performance of other models.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Comparing classifier performance with baselines. (read)

Unfortunately, baselines are often overlooked and, in the presence of a class imbalance, must be established with care.

Megahed, F.M, Chen, Y-J., Jones-Farmer, A., Rigdon, S.E., Krzywinski, M. & Altman, N. (2024) Points of significance: Comparing classifier performance with baselines. Nat. Methods 21:546–548.

Happy 2024 π Day—
sunflowers ho!

Sat 09-03-2024

Celebrate π Day (March 14th) and dig into the digit garden. Let's grow something.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
2024 π DAY | A garden of 1,000 digits of π. (details)

How Analyzing Cosmic Nothing Might Explain Everything

Thu 18-01-2024

Huge empty areas of the universe called voids could help solve the greatest mysteries in the cosmos.

My graphic accompanying How Analyzing Cosmic Nothing Might Explain Everything in the January 2024 issue of Scientific American depicts the entire Universe in a two-page spread — full of nothing.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
How Analyzing Cosmic Nothing Might Explain Everything. Text by Michael Lemonick (editor), art direction by Jen Christiansen (Senior Graphics Editor), source: SDSS

The graphic uses the latest data from SDSS 12 and is an update to my Superclusters and Voids poster.

Michael Lemonick (editor) explains on the graphic:

“Regions of relatively empty space called cosmic voids are everywhere in the universe, and scientists believe studying their size, shape and spread across the cosmos could help them understand dark matter, dark energy and other big mysteries.

To use voids in this way, astronomers must map these regions in detail—a project that is just beginning.

Shown here are voids discovered by the Sloan Digital Sky Survey (SDSS), along with a selection of 16 previously named voids. Scientists expect voids to be evenly distributed throughout space—the lack of voids in some regions on the globe simply reflects SDSS’s sky coverage.”

voids

Sofia Contarini, Alice Pisani, Nico Hamaus, Federico Marulli Lauro Moscardini & Marco Baldi (2023) Cosmological Constraints from the BOSS DR12 Void Size Function Astrophysical Journal 953:46.

Nico Hamaus, Alice Pisani, Jin-Ah Choi, Guilhem Lavaux, Benjamin D. Wandelt & Jochen Weller (2020) Journal of Cosmology and Astroparticle Physics 2020:023.

Sloan Digital Sky Survey Data Release 12

constellation figures

Alan MacRobert (Sky & Telescope), Paulina Rowicka/Martin Krzywinski (revisions & Microscopium)

stars

Hoffleit & Warren Jr. (1991) The Bright Star Catalog, 5th Revised Edition (Preliminary Version).

cosmology

H0 = 67.4 km/(Mpc·s), Ωm = 0.315, Ωv = 0.685. Planck collaboration Planck 2018 results. VI. Cosmological parameters (2018).

Error in predictor variables

Tue 02-01-2024

It is the mark of an educated mind to rest satisfied with the degree of precision that the nature of the subject admits and not to seek exactness where only an approximation is possible. —Aristotle

In regression, the predictors are (typically) assumed to have known values that are measured without error.

Practically, however, predictors are often measured with error. This has a profound (but predictable) effect on the estimates of relationships among variables – the so-called “error in variables” problem.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Error in predictor variables. (read)

Error in measuring the predictors is often ignored. In this column, we discuss when ignoring this error is harmless and when it can lead to large bias that can leads us to miss important effects.

Altman, N. & Krzywinski, M. (2024) Points of significance: Error in predictor variables. Nat. Methods 21:4–6.

Background reading

Altman, N. & Krzywinski, M. (2015) Points of significance: Simple linear regression. Nat. Methods 12:999–1000.

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of significance: Logistic regression. Nat. Methods 13:541–542 (2016).

Das, K., Krzywinski, M. & Altman, N. (2019) Points of significance: Quantile regression. Nat. Methods 16:451–452.

Martin Krzywinski | contact | Canada's Michael Smith Genome Sciences CentreBC Cancer Research CenterBC CancerPHSA
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