genomics + data mining
ICDM2012 Keynote
Needles in Stacks of Needles: genomics + data mining
visual abstract
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.
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.