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Molecular Systems Biology
Scopus
ISSN 1744-4292 · Springer Nature · 1,487 articles in the index
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Journal Article
The DNA dialect: a comprehensive guide to pretrained genomic language models
Abstract Following their success in natural language processing and protein biology, pretrained large language models have started appearing in genomics in large numbers. These genomic language models (gLMs), trained on diverse DNA and RNA sequences, promise improved performance on a variety of…
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Journal Article
Single-cell analysis reveals critical toxin/antitoxin ratio triggering persister resuscitation
Abstract Persisters represent a transient, antibiotic-tolerant subpopulation within isogenic bacterial populations, contributing to infection relapses. However, the mechanisms driving persister formation and resuscitation remain elusive. Here, we developed nano-flow cytometry (nFCM)-based methods…
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Journal Article
Pooled single-cell screen in colorectal cancer defines transcriptional modules linked to oncogenes
Abstract Oncogenic mutations shape colorectal cancer (CRC) biology, yet their impact on transcriptional phenotypes remains incompletely understood, and their individual prognostic value is limited. Here, we perform a pooled single-cell transcriptomic screen of over 100,000 CRC cells with a…
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Journal Article
Limited proteolysis-coupled mass spectrometry captures proteome-wide protein structural alterations and biomolecular condensation in living cells
Abstract The function of a protein is determined by its structure, which may change dynamically in response to post-translational modifications, interaction with other molecules, or environmental factors like temperature. Limited proteolysis-coupled mass spectrometry (LiP-MS) captures such…
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Journal Article
The evolutionary dynamics between viral mimics and host proteins
Abstract Viral proteins interact with host proteins to hijack cellular pathways important for viral replication. Viral mimics are proteins whose structural similarity to host-mimicked proteins allows them to interact with mutual host targets. This mimicry poses a challenge for the host—how to avoid…
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Journal Article
A universal surface functionalization technique to chemically enhance live microbial cells
Abstract Microbial surface functionalization is a powerful strategy for endowing microbes with novel, non-genetic functions. However, existing methods are often species-specific, limited in scope, and compromise cell viability. Here, we present a universal and modular platform for high-density…
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Journal Article
Identifying clinically relevant cell state interactions in the tumor microenvironment of IDH-mutant gliomas using CSI-TME
Abstract Tumor microenvironment (TME) is characterized by a milieu of distinct cell types that exist in heterogenous transcriptional states across tumors. Functional interactions among these cell states drive tumor progression and therapy response. Systematic characterization of functional…
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Journal Article
SyntheMol-RL: a flexible reinforcement learning framework for designing easily synthesizable antibiotics
Abstract The rise of antibiotic-resistant pathogens such as Staphylococcus aureus has created an urgent need for new antibiotics. Generative artificial intelligence (AI) has shown promise in drug discovery, but existing models often fail to propose compounds that are both effective and…
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Journal Article
VEFill: accurate and generalizable deep mutational scanning score imputation across protein domains
Abstract Deep Mutational Scanning (DMS) assays can systematically assess the effects of amino acid substitutions on protein function, but many datasets have incomplete variant coverage due to technical constraints. We developed VEFill (Variant Effect Fill), a gradient boosting model for imputing…
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Journal Article
Common xenobiotics modulate gut microbial responses to low‑calorie sweeteners in vitro
Abstract The gut microbiota is implicated in adverse effects associated with low-calorie sweeteners. Yet, the direct impact of sweeteners on gut bacteria remains largely uncharacterized. Here, we report interactions between 25 phylogenetically diverse gut bacterial strains and 39 commercially used…
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Journal Article
Paradoxical non-catalytic kinase functions are driven by inhibitor-induced displacement of autoinhibitory domains
Abstract ATP-competitive kinase inhibitors represent one of the largest classes of targeted anti-cancer drugs. While their primary mechanism is to block catalytic activity, they can also trigger paradoxical phenotypic effects that cannot be explained by catalytic inhibition alone. These…
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Journal Article
Engineered E. coli swarming for binary and analog input recording
Abstract Many bacterial species form self-organized macroscale patterns through swarming. Despite its extensive genetic tractability, Escherichia coli remains underexplored for robust, applied control of swarming. Here we develop a set of E. coli strains that generate centimeter-scale swarming…
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Journal Article
Interpretable multi-omics integration across mixed-order tensors with MANTRA
Abstract The integration of multi-modal molecular data is crucial for understanding complex diseases, but existing methods struggle with modern experimental designs that generate datasets with mixed-order tensors—for example, a third-order drug–response tensor alongside a second-order…
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Journal Article
Quantitative interactome mapping of skeletal muscle insulin resistance
Abstract Protein-protein interactions (PPIs) are dynamic and critical to adaptive homeostasis. While there have been massive efforts to catalogue proteome-wide PPIs, global quantification of changes remains a challenge. Here, we integrate dynamic protein correlation profiling - mass spectrometry…
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Journal Article
To cleave or not to cleave: a systemic evaluation of DSS versus DSSO for cross-linking mass spectrometry analysis
Abstract Cross-linking mass spectrometry is a powerful method for structural analysis, but choosing between cleavable and non-cleavable cross-linkers remains challenging. We rigorously compared non-cleavable DSS with cleavable DSSO and found that DSS consistently yields more cross-link…
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Journal Article
Cross-species insights from ART-D to uncover evolutionarily conserved oncogenic mechanisms
Abstract Cancer arises from oncogenic clones, yet the dynamic mechanisms driving their stepwise evolution toward malignancy remain incompletely understood. Here, we establish the Atlas of Ras-driven Tumors in Drosophila (ART-D), a systematic, cross-species platform that dissects the molecular and…
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Journal Article
Burst of aneuploidy: a cost of adaptation driven by breakdown of cell cycle control
Abstract Complex genome rearrangements are intriguing because it remains unclear whether they occurred gradually or suddenly, and what promoted or impeded their development. We started by asking whether double loss of heterozygosity (dLOH) involving two different chromosomes is simply the result of…
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Journal Article
Immunoglobulin sub-class levels define inter-donor plasma variability: a longitudinal dual-lab study
Abstract Advances in mass spectrometry have transformed plasma proteomics, allowing high-throughput analysis of large cohorts. This study utilized the TIMES (Tracking Individuals Monthly for Evaluating Stability) cohort, consisting of 51 healthy participants monitored monthly over 12 months, to…
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Journal Article
Cell painting and thermal proteome profiling for inference of drug targets and mechanism of action
Abstract Understanding the mechanism of action (MoA) of bioactive compounds is a central challenge in drug discovery and chemical biology. We propose a strategy for integrating morphological data with proteomics to provide deeper insights into the MoA of compounds. We combine the rich phenotypic…
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