Our featured article: Adapting systems biology to address the complexity of human disease in the single-cell era go.nature.com/3XBo6Vh #Review by @davidsebfischer.bsky.social, Martin A. Villanueva, Peter S. Winter & ‪@shaleklab.bsky.social‬ @broadinstitute.org @mit.edu @ragoninstitute.bsky.social

This review is a product of a great team effort together with Martin Villanueva, Peter Winter and Alex Shalek! www.nature.com/articles/s41... & rdcu.be/ecTna

In summary, we outline how systems biology is being adapted to the multiscale dynamics of human health and disease in omics-driven as what is effectively a two-loop cycle over discovery and validation.

We review strategies that can manage this distance and dissect how it relates to understanding cellular systems at specific spatiotemporal scales - be it the cellular scale often considered in the context of single-cell-resolved experiments, or the tissue niche scale captured with spatial omics.

Both are needed to build quantitative models are faithful to human biology and validated through perturbation experiments. However, the usage of two distinct systems incurs a "translational distance" that complicates systems biology approaches that utilize information from the two.

In this review, we discuss how one can rationalize what information about a multiscale cellular system is actually captured by on omics study. We leverage that insight to describe how one can translate between discovery efforts in human tissues and validation efforts in experimental model systems.

However, the dynamics of human tissues in disease settings is multiscale - not only does that impact quantitative models, it also reflects in experimental design and the resources of publicly available data that we have access to. This obstructs attempts at building such quantitative models.

You are already in this one @jasmineplummer.bsky.social!