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research: revealing


EMBO Practical Course: Bioinformatics and Genome Analysis, 5–17 June 2017.


data visualization + art

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The BC Cancer Agency’s Personalized Oncogenomics Program (POG) is a clinical research initiative applying genomic sequencing to the diagnosis and treatment of patients with incurable cancers.

Art of the Personalized Oncogenomics Program

Nature uses only the longest threads to weave her patterns, so that each small piece of her fabric reveals the organization of the entire tapestry.
— Richard Feynman

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The POG art shows 545 cases studied over the course of 5 years and is freely available as posters for printing and images for your desktop and presentation slides in both bitmap and PDF formats.

 / 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. (zoom)

 / 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. (zoom)

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.

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.

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).

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. (zoom)

 / 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. (zoom)

 / 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. (zoom)

 / 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. (zoom)
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news + thoughts

Classification and regression trees

Fri 28-07-2017
Decision trees are a powerful but simple prediction method.

Decision trees classify data by splitting it along the predictor axes into partitions with homogeneous values of the dependent variable. Unlike logistic or linear regression, CART does not develop a prediction equation. Instead, data are predicted by a series of binary decisions based on the boundaries of the splits. Decision trees are very effective and the resulting rules are readily interpreted.

Trees can be built using different metrics that measure how well the splits divide up the data classes: Gini index, entropy or misclassification error.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Classification and decision trees. (read)

When the predictor variable is quantitative and not categorical, regression trees are used. Here, the data are still split but now the predictor variable is estimated by the average within the split boundaries. Tree growth can be controlled using the complexity parameter, a measure of the relative improvement of each new split.

Individual trees can be very sensitive to minor changes in the data and even better prediction can be achieved by exploiting this variability. Using ensemble methods, we can grow multiple trees from the same data.

Krzywinski, M. & Altman, N. (2017) Points of Significance: Classification and regression trees. Nature Methods 14:757–758.

Background reading

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of Significance: Logistic regression. Nature Methods 13:541-542.

Altman, N. & Krzywinski, M. (2015) Points of Significance: Multiple Linear Regression Nature Methods 12:1103-1104.

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of Significance: Classifier evaluation. Nature Methods 13:603-604.

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of Significance: Model Selection and Overfitting. Nature Methods 13:703-704.

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of Significance: Regularization. Nature Methods 13:803-804.

...more about the Points of Significance column

Personal Oncogenomics Program 5 Year Anniversary Art

Wed 26-07-2017

The artwork was created in collaboration with my colleagues at the Genome Sciences Center to celebrate the 5 year anniversary of the Personalized Oncogenomics Program (POG).

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

The Personal Oncogenomics Program (POG) is a collaborative research study including many BC Cancer Agency oncologists, pathologists and other clinicians along with Canada's Michael Smith Genome Sciences Centre with support from BC Cancer Foundation.

The aim of the program is to sequence, analyze and compare the genome of each patient's cancer—the entire DNA and RNA inside tumor cells— in order to understand what is enabling it to identify less toxic and more effective treatment options.

Principal component analysis

Thu 06-07-2017
PCA helps you interpret your data, but it will not always find the important patterns.

Principal component analysis (PCA) simplifies the complexity in high-dimensional data by reducing its number of dimensions.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Principal component analysis. (read)

To retain trend and patterns in the reduced representation, PCA finds linear combinations of canonical dimensions that maximize the variance of the projection of the data.

PCA is helpful in visualizing high-dimensional data and scatter plots based on 2-dimensional PCA can reveal clusters.

Altman, N. & Krzywinski, M. (2017) Points of Significance: Principal component analysis. Nature Methods 14:641–642.

Background reading

Altman, N. & Krzywinski, M. (2017) Points of Significance: Clustering. Nature Methods 14:545–546.

...more about the Points of Significance column

`k` index: a weightlighting and Crossfit performance measure

Wed 07-06-2017

Similar to the `h` index in publishing, the `k` index is a measure of fitness performance.

To achieve a `k` index for a movement you must perform `k` unbroken reps at `k`% 1RM.

The expected value for the `k` index is probably somewhere in the range of `k = 26` to `k=35`, with higher values progressively more difficult to achieve.

In my `k` index introduction article I provide detailed explanation, rep scheme table and WOD example.

Dark Matter of the English Language—the unwords

Wed 07-06-2017

I've applied the char-rnn recurrent neural network to generate new words, names of drugs and countries.

The effect is intriguing and facetious—yes, those are real words.

But these are not: necronology, abobionalism, gabdologist, and nonerify.

These places only exist in the mind: Conchar and Pobacia, Hzuuland, New Kain, Rabibus and Megee Islands, Sentip and Sitina, Sinistan and Urzenia.

And these are the imaginary afflictions of the imagination: ictophobia, myconomascophobia, and talmatomania.

And these, of the body: ophalosis, icabulosis, mediatopathy and bellotalgia.

Want to name your baby? Or someone else's baby? Try Ginavietta Xilly Anganelel or Ferandulde Hommanloco Kictortick.

When taking new therapeutics, never mix salivac and labromine. And don't forget that abadarone is best taken on an empty stomach.

And nothing increases the chance of getting that grant funded than proposing the study of a new –ome! We really need someone to looking into the femome and manome.

Dark Matter of the Genome—the nullomers

Wed 31-05-2017

An exploration of things that are missing in the human genome. The nullomers.

Julia Herold, Stefan Kurtz and Robert Giegerich. Efficient computation of absent words in genomic sequences. BMC Bioinformatics (2008) 9:167