Art of the Personalized Oncogenomics Program
In research the horizon recedes as we advance, and is no nearer at sixty than it was at twenty. As the power of endurance weakens with age, the urgency of the pursuit grows more intense ... And research is always incomplete.
— Mark Pattison (Isaac Casaubon)
contents
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.
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.
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.
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).
In additional to the posters, I've created remixes for your desktop at 4k resolution.
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).
You can purchase your own data-powered and human-driven cycling jersey.
Happy 2025 π Day—
TTCAGT: a sequence of digits
Celebrate π Day (March 14th) and sequence digits like its 1999. Let's call some peaks.
Crafting 10 Years of Statistics Explanations: Points of Significance
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.
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
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.
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
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.
Altman, N. & Krzywinski, M. (2024) Understanding p-values and significance. Laboratory Animals 58:443–446.
Depicting variability and uncertainty using intervals and error bars
Variability is inherent in most biological systems due to differences among members of the population. Two types of variation are commonly observed in studies: differences among samples and the “error” in estimating a population parameter (e.g. mean) from a sample. While these concepts are fundamentally very different, the associated variation is often expressed using similar notation—an interval that represents a range of values with a lower and upper bound.
In this article we discuss how common intervals are used (and misused).
Altman, N. & Krzywinski, M. (2024) Depicting variability and uncertainty using intervals and error bars. Laboratory Animals 58:453–456.
Nasa to send our human genome discs to the Moon
We'd like to say a ‘cosmic hello’: mathematics, culture, palaeontology, art and science, and ... human genomes.
