Publications

Genotype-phenotype relationships are mediated through intricate networks of physical and functional interactions among macromolecules. Knowledge of the interactome is vital to understand and model genetics and cellular biology. Recent advances in accurately predicting tertiary protein structures using artificial intelligence (AI) approaches such as AlphaFold¹ have revived the vision that the protein-protein interactome might be fully predictable through computational modeling of quaternary...

The 2025 Voice AI Symposium represented a transition from conceptual research to clinical implementation in vocal biomarker science. Hosted by the NIH-funded Bridge2AI-Voice consortium, the meeting convened global experts to address the methodological, ethical, and translational challenges of integrating voice-based artificial intelligence (AI) into healthcare. This mini-review synthesizes symposium insights across six domains: multimodal integration, FAIR (Findable, Accessible, Interoperable,...

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Cells and organisms adjust their growth based on the availability of cholesterol, which is essential for cellular functions. However, the mechanisms by which cells sense cholesterol levels and translate these into growth signals are not fully understood. We report that cholesterol rapidly activates the master growth-regulatory TOR pathway in Drosophila tissues. We identify the nuclear receptor HR3, an ortholog of mammalian RORα, as an essential factor in cholesterol-induced TOR activation. We...

How will peer pressure among sellers affect their operations in an online marketplace? Motivated by online platforms' marketplace designs that prompt sellers to compare their performances, in this paper, we develop and study a price competition model in which sellers account for both profits and peer comparison outcomes. In our model, two sellers offer substitutable products, and each of them sets a price ex ante to maximize their expected total utility, which is the sum of one's profit and the...

Across biological subdisciplines, the last decade has seen an explosion of high-dimensional datasets. At the ICTS workshop ‘Unifying Theories in High-Dimensional Biophysics’, we discussed whether this high dimensionality poses a challenge or an opportunity for theoretically describing, understanding and predicting biological systems. We discussed methods, models and frameworks that can be used for this purpose. This Comment summarizes our discussions from the perspectives of individual...

CONCLUSIONS: Integrating subgroup-specific genetic events with clinical features facilitates MB risk stratification, informs context-dependent radiotherapy consideration, and provides actionable candidates for prospective validation.

Genetic interaction networks map functional connections between genes and their corresponding pathways and complexes. We previously developed TheCellMap.org as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) analysis in the budding yeast, Saccharomyces cerevisiae. We have expanded TheCellMap.org to include ~89,000 quantitative genetic interactions identified from genome-scale CRISPR-based analysis of ~4...

Cell-to-cell transmission of human immunodeficiency virus (HIV) presents a significant challenge to combination antiretroviral therapy (cART), as this mode of infection is markedly more efficient and often exhibits increased resistance to antiviral agents compared to cell-free viral infection. However, the impact of cell-to-cell virus transmission on the efficacy of broadly neutralizing antibody (bNAb) therapy remains unclear. In this study, we develop a mathematical model that incorporates both...

The oil refinery (OR) consortium is a model methanogenic enrichment culture used to study anaerobic benzene degradation. Over half of the culture's bacterial community consists of two closely related Desulfobacterota strains, designated ORM2a and ORM2b, whose mechanisms of benzene activation are unknown. Three proteomics data sets were integrated and analyzed using high-quality OR metagenomes and metagenome-assembled genomes (MAGs), including a complete circularized ORM2a MAG, to identify active...

Guidelines for managing scientific data have been established under the FAIR principles, requiring that data be Findable, Accessible, Interoperable, and Reusable. In many scientific disciplines, especially computational biology, both data and models are key to progress. For this reason, and recognizing that such models are a very special type of "data", we argue that computational models, especially mechanistic models prevalent in medicine, physiology and systems biology, deserve a complementary...

Climate change forces species to adapt rapidly to avoid extinction. To directly observe rapid adaptation and extinction, we conducted synchronized evolution experiments with Arabidopsis thaliana in 30 locations across Western Europe, the Mediterranean, the Levant, and North America. Whole-genome pooled sequencing of ~70,000 surviving plants revealed repeatable allele frequency shifts in similar climates but divergent shifts across contrasting ones, indicating evolutionary adaptation. We...

Single-cell RNA sequencing (scRNA-seq) allows transcriptional profiling, and cell-type annotation of individual cells. However, sample preparation in typical scRNA-seq experiments often homogenizes the samples, thus spatial locations of individual cells are often lost. Although spatial transcriptomic techniques, such as in situ hybridization (ISH) or Slide-seq, can be used to measure gene expression in specific locations in samples, it remains a challenge to measure or infer expression level for...

Posterior fossa type A (PFA) ependymoma is an unusual infantile brain tumour with few known somatic mutations, thought to be driven by epigenetic mechanisms¹. PFA ependymoma has a markedly higher incidence and worse prognosis in male children than in female children². The mechanisms that underlie these sex differences are at present unknown. Here we show that the cellular hierarchy of PFA ependymoma is less differentiated in male individuals than it is in female individuals. In the normal...

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CONCLUSIONS: Our results demonstrate that glomeruli and their components undergo dramatic and often divergent stiffness changes following different types of injury. Interestingly, podocyte softening is a common manifestation of proteinuric kidney diseases, a phenomenon that is associated with inactivation of transcription co-factors that maintain normal podocyte structure and function.

The accumulation of per- and polyfluoroalkyl substances (PFAS) in human tissues is known. However, PFAS accumulation in the lung tissue of lung cancer patients remains unexplored. We examined the distribution of 26 PFAS in lung tissues and found a total concentration ranging from 0.75 to 368 ng/g, with perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) identified as predominant compounds. Perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkyl sulfonic acids (PFSAs) were the most...

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To define and systematically characterize the human E3 ubiquitin ligase (E3) landscape, we generated the E3-ome, a compendium of E3s encoded by the human genome. The E3-ome integrates experimental data, bioinformatics, and published research, revealing 672 high-confidence E3s. We standardized E3 classifications to create a unified framework for annotation and comparative analysis. The E3-ome identified several previously unrecognized domains, motifs, E3 candidates, and relationships, expanding...

Artificial intelligence (AI) has the potential to transform health care; however, successful integration of AI into health care requires overcoming obstacles, such as biases in data and AI models, and addressing challenges in generating sufficient clinical evidence for deployment. In this Viewpoint, we present a community-based, actionable framework for responsible and ethical development, deployment, and integration of AI-based solutions in health care, emphasising bias mitigation and clinical...