Arc Research

A high-resolution protein-RNA binding atlas for structure-aware interaction prediction and post-transcriptional regulatory modeling
BioRxiv
Goodarzi Lab

A high-resolution protein-RNA binding atlas for structure-aware interaction prediction and post-transcriptional regulatory modeling

RNA-binding proteins control post-transcriptional gene expression by regulating RNA processing, localization, stability, and translation. Here we introduce a high-throughput CLIP-seq platform that combines endogenous protein tagging for uniform affinity capture with ligation-free library preparation to generate high-resolution RNA-protein binding profiles.

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The adaptive architecture of tRNA dependencies across physiological tumor environments
BioRxiv
Goodarzi Lab

The adaptive architecture of tRNA dependencies across physiological tumor environments

The genetic code is decoded by a highly redundant transfer RNA (tRNA) repertoire. Here, we establish an atlas of tRNA dependencies through large-scale CRISPRi perturbation mapping across matched in vivo tumor growth and in vitro cell culture for 16 cancer cell lines spanning seven tissue types.

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PIE: Generalizing perturbation effects across unseen perturbations, contexts and datasets
BioRxiv
Computational

PIE: Generalizing perturbation effects across unseen perturbations, contexts and datasets

Predicting cellular response to perturbations is key to understanding biological mechanisms and selecting therapeutic targets. Here, we introduce PIE, a model that addresses these limitations by reformulating the learning task around population level perturbation effects and incorporating auxiliary inputs that better characterize the biological system.

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Extracellular cGAMP transmission exacerbates neuroinflammation in aging and multiple sclerosis
BioRxiv
Li Lab

Extracellular cGAMP transmission exacerbates neuroinflammation in aging and multiple sclerosis

Neuroinflammation drives neurodegeneration and cognitive decline in aging, but the signals that spread this inflammation across the CNS remain unclear. Here, we show in mice that advanced age and experimental autoimmune encephalomyelitis both result in elevated cytosolic mtDNA in microglia.

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Coevolutionary mining of prokaryotic non-coding elements with a genome language mode
BioRxiv
Hie Lab

Coevolutionary mining of prokaryotic non-coding elements with a genome language mode

Microbial genomes encode essential ncRNAs and nucleic-acid-interacting proteins. However, discovery of these systems remains based on similarity to known sequences. Here, we introduce Minerva, a framework for coevolutionary mining that uses genome language models to predict pairwise interactions directly from sequence.

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Tahoe-100M: Mapping drug-induced molecular phenotypes at single-cell resolution
Cell
Goodarzi LabComputational

Tahoe-100M: Mapping drug-induced molecular phenotypes at single-cell resolution

Tahoe-100M, generated by Tahoe, is a giga-scale single-cell perturbation atlas comprising 100 million transcriptomes from 50 diverse cancer cell lines treated with 1,100 drug-dose conditions. This parallel profiling of thousands of perturbations at single-cell resolution with minimal batch effects is enabled by the Mosaic platform.

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scBaseCount: An AI agent-curated, standardized, auto-updated single-cell data repository
Cell
Computational

scBaseCount: An AI agent-curated, standardized, auto-updated single-cell data repository

Here, we introduce scBaseCount, a database that leverages an AI agent to automate discovery and metadata extraction and standardize data processing. It is the largest public repository of single-cell gene expression data, comprising over 502 million cells across 27 organisms and 75 tissues.

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ENPP1 buffers extracellular cGAMP in brown adipose tissue to limit insulin resistance
Cell Reports
Li Lab

ENPP1 buffers extracellular cGAMP in brown adipose tissue to limit insulin resistance

The mechanism underlying the role of ENPP1 in metabolic disease remains unsolved. Using a 2′3′-cyclic GMP-AMP (cGAMP)-hydrolysis-deficient mouse (Enpp1H362A), we show that selective loss of this activity exacerbates high-fat diet (HFD)-induced weight gain and insulin resistance.

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Chemogenomic maps reveal a PRDX1-dependent iron–damage axis in the DNA damage response
Nature Chemical Biology
Gilbert Lab

Chemogenomic maps reveal a PRDX1-dependent iron–damage axis in the DNA damage response

The DNA damage response (DDR) is a sophisticated network of cellular pathways whose perturbation leads to genome instability and is a key hallmark of oncogenesis. Here, we present data from 32 genome-scale loss-of-function CRISPR interference chemical–genetic screens with inhibitors targeting core constituents of the DDR machinery.

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The diversity of terminal electron acceptors across eukaryotes
Trends in Biochemical Sciences
Jain LabReview

The diversity of terminal electron acceptors across eukaryotes

his review summarizes respiratory and fermentative electron acceptors across eukaryotes, focusing on the evolution of anaerobic pathways. We highlight how ancient metabolic strategies have been conserved and modified to support organisms’ adaptation to diverse environmental niches and to sustain biological resilience.

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