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data: beautiful



Circos at British Library Beautiful Science exhibit—Feb 20–May 26


genomics + data mining

ICDM2012 Keynote

Needles in Stacks of Needles: genomics + data mining

Download talk

visual abstract

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The talk introduces genomics and cancer biology to computer scientists and outlines areas in which data mining methods are being used to further our understanding of the genome. The theme is one of complexity and relevance — computers manage the former, but we are the ultimate judges of the latter. (download talk, ICDM2012)

abstract

In 2001, the first human genome sequence was published. Now, just over 10 years later, we capable of sequencing a genome in just a few days. Massive parallel sequencing projects now make it possible to study the cancers of thousands of individuals. New data mining approaches are required to robustly interrogate the data for causal relationships among the inherently noisy biology. How does one identify genetic changes that are specific and causal to a disease within the rich variation that is either natural or merely correlated? The problem is one of finding a needle in a stack of needles. I will provide a non-specialist introduction to data mining methods and challenges in genomics, with a focus on the role visualization plays in the exploration of the underlying data.

references

The title of the talk was drawn from the paper

Gregory M. Cooper & Jay Shendure Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data Nature Reviews Genetics 12, 628-640 (September 2011)

I will be posting a full list of references for the talk shortly.

news + thoughts

Happy Pi Approximation Day— π, roughly speaking 10,000 times

Wed 23-07-2014

Celebrate Pi Approximation Day (July 22nd) with the art arm waving. This year I take the first 10,000 most accurate approximations (m/n, m=1..10,000) and look at their accuracy.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Accuracy of the first 10,000 m/n approximations of Pi. (details)

I turned to the spiral again after applying it to stack stacked ring plots of frequency distributions in Pi for the 2014 Pi Day.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Frequency distribution of digits of Pi in groups of 4 up to digit 4,988. (details)

Analysis of Variance (ANOVA) and Blocking—Accounting for Variability in Multi-factor Experiments

Mon 07-07-2014

Our 10th Points of Significance column! Continuing with our previous discussion about comparative experiments, we introduce ANOVA and blocking. Although this column appears to introduce two new concepts (ANOVA and blocking), you've seen both before, though under a different guise.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Analysis of variance (ANOVA) and blocking. (read)

If you know the t-test you've already applied analysis of variance (ANOVA), though you probably didn't realize it. In ANOVA we ask whether the variation within our samples is compatible with the variation between our samples (sample means). If the samples don't all have the same mean then we expect the latter to be larger. The ANOVA test statistic (F) assigns significance to the ratio of these two quantities. When we only have two-samples and apply the t-test, t2 = F.

ANOVA naturally incorporates and partitions sources of variation—the effects of variables on the system are determined based on the amount of variation they contribute to the total variation in the data. If this contribution is large, we say that the variation can be "explained" by the variable and infer an effect.

We discuss how data collection can be organized using a randomized complete block design to account for sources of uncertainty in the experiment. This process is called blocking because we are blocking the variation from a known source of uncertainty from interfering with our measurements. You've already seen blocking in the paired t-test example, in which the subject (or experimental unit) was the block.

We've worked hard to bring you 20 pages of statistics primers (though it feels more like 200!). The column is taking a month off in August, as we shrink our error bars.

Krzywinski, M. & Altman, N. (2014) Points of Significance: Analysis of Variance (ANOVA) and Blocking Nature Methods 11:699-700.

Background reading

Krzywinski, M. & Altman, N. (2014) Points of Significance: Designing Comparative Experiments Nature Methods 11:597-598.

Krzywinski, M. & Altman, N. (2014) Points of Significance: Comparing Samples — Part I — t-tests Nature Methods 11:215-216.

Krzywinski, M. & Altman, N. (2013) Points of Significance: Significance, P values and t-tests Nature Methods 10:1041-1042.

...more about the Points of Significance column

Designing Experiments—Coping with Biological and Experimental Variation

Thu 29-05-2014

This month, Points of Significance begins a series of articles about experimental design. We start by returning to the two-sample and paired t-tests for a discussion of biological and experimental variability.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Designing Comparative Experiments. (read)

We introduce the concept of blocking using the paired t-test as an example and show how biological and experimental variability can be related using the correlation coefficient, ρ, and how its value imapacts the relative performance of the paired and two-sample t-tests.

We also emphasize that when reporting data analyzed with the paired t-test, differences in sample means (and their associated 95% CI error bars) should be shown—not the original samples—because the correlation in the samples (and its benefits) cannot be gleaned directly from the sample data.

Krzywinski, M. & Altman, N. (2014) Points of Significance: Designing Comparative Experiments Nature Methods 11:597-598.

Background reading

Krzywinski, M. & Altman, N. (2014) Points of Significance: Comparing Samples — Part I — t-tests Nature Methods 11:215-216.

Krzywinski, M. & Altman, N. (2013) Points of Significance: Significance, P values and t-tests Nature Methods 10:1041-1042.

Have skew, will test

Wed 28-05-2014

Our May Points of Significance Nature Methods column jumps straight into dealing with skewed data with Non Parametric Tests.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Non Parametric Testing. (read)

We introduce non-parametric tests and simulate data scenarios to compare their performance to the t-test. You might be surprised—the t-test is extraordinarily robust to distribution shape, as we've discussed before. When data is highly skewed, non-parametric tests perform better and with higher power. However, if sample sizes are small they are limited to a small number of possible P values, of which none may be less than 0.05!

Krzywinski, M. & Altman, N. (2014) Points of Significance: Non Parametric Testing Nature Methods 11:467-468.

Background reading

Krzywinski, M. & Altman, N. (2014) Points of Significance: Comparing Samples — Part I — t-tests Nature Methods 11:215-216.

Krzywinski, M. & Altman, N. (2013) Points of Significance: Significance, P values and t-tests Nature Methods 10:1041-1042.

Mind your p's and q's

Sat 29-03-2014

In the April Points of Significance Nature Methods column, we continue our and consider what happens when we run a large number of tests.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Comparing Samples — Part II — Multiple Testing. (read)

Observing statistically rare test outcomes is expected if we run enough tests. These are statistically, not biologically, significant. For example, if we run N tests, the smallest P value that we have a 50% chance of observing is 1–exp(–ln2/N). For N = 10k this P value is Pk=10kln2 (e.g. for 104=10,000 tests, P4=6.9×10–5).

We discuss common correction schemes such as Bonferroni, Holm, Benjamini & Hochberg and Storey's q and show how they impact the false positive rate (FPR), false discovery rate (FDR) and power of a batch of tests.

Krzywinski, M. & Altman, N. (2014) Points of Significance: Comparing Samples — Part II — Multiple Testing Nature Methods 11:215-216.

Krzywinski, M. & Altman, N. (2014) Points of Significance: Comparing Samples — Part I — t-tests Nature Methods 11:215-216.

Krzywinski, M. & Altman, N. (2013) Points of Significance: Significance, P values and t-tests Nature Methods 10:1041-1042.