Brain signaling becomes less integrated and more segregated with age.

The integration-segregation framework is a popular first step to understand brain dynamics because it simplifies brain dynamics into two states based on global versus local signaling patterns. However, there is no consensus for how to best define the two states. Here, we map integration and segregation to order and disorder states from the Ising model in physics to calculate state probabilities, and , from functional MRI data.

Normal tissue transcriptional signatures for tumor-type-agnostic phenotype prediction.

Cancer transcriptional patterns reflect both unique features and shared hallmarks across diverse cancer types, but whether differences in these patterns are sufficient to characterize the full breadth of tumor phenotype heterogeneity remains an open question. We hypothesized that these shared transcriptomic signatures reflect repurposed versions of functional tasks performed by normal tissues. Starting with normal tissue transcriptomic profiles, we use non-negative matrix factorization to derive six distinct transcriptomic phenotypes, called archetypes, which combine to describe both normal tissue patterns and variations across a broad spectrum of malignancies.

Origins of Life: The Protein Folding Problem all over again?

How did specific useful protein sequences arise from simpler molecules at the origin of life? This seemingly needle-in-a-haystack problem has remarkably close resemblance to the old Protein Folding Problem, for which the solution is now known from statistical physics. Based on the logic that Origins must have come only after there was an operative evolution mechanism-which selects on phenotype, not genotype-we give a perspective that proteins and their folding processes are likely to have been the primary driver of the early stages of the origin of life.

The prebiotic emergence of biological evolution.

The origin of life must have been preceded by Darwin-like evolutionary dynamics that could propagate it. How did that adaptive dynamics arise? And from what prebiotic molecules? Using evolutionary invasion analysis, we develop a universal framework for describing any origin story for evolutionary dynamics. We find that autocatalysts, i.

Transcriptional drift in aging cells: A global decontroller.

As cells age, they undergo a remarkable global change: In transcriptional drift, hundreds of genes become overexpressed while hundreds of others become underexpressed. Using archetype modeling and Gene Ontology analysis on data from aging worms, we find that the up-regulated genes code for sensory proteins upstream of stress responses and down-regulated genes are growth- and metabolism-related. We observe similar trends within human fibroblasts, suggesting that this process is conserved in higher organisms.