Nature Genetics Cover — August 2020 issue
Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade–specific epigenome and transcriptome landscapes
Gagliardi, A., Porter, V.L., Zong, Z. et al. (2020) Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade–specific epigenome and transcriptome landscapes. Nature Genetics 52:800–810.
Nature Genetics selected our design for the cover of the August 2020 issue. The design is based on histone modifications across HPV-integration events, which we report on in Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade–specific epigenome and transcriptome landscapes.
The piece's title “Dichotomy of Chromatin in Color” was suggested by Dr. Andy Mungall, one of the senior authors on the report.
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about the cover
As reported by Gagliardi et al. in Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade–specific epigenome and transcriptome landscapes, human papillomavirus (HPV) is found integrated within the genome in most cervical tumors, and often is associated with marked epigenetic and transcriptional activation of the surrounding chromatin. The circular arrangement shows the profile of histone modifications observed with ChIP–seq across the HPV-integration events in the cluster with the highest increase in enrichment. It is composed of data sampled from two randomly paired individuals, with tracks facing inward and outward for each individual. Individuals are paired randomly, and track colors correspond to five histone marks with epigenetic enrichment.
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.