Genetics

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A Generalizable Machine Learning Framework for cfDNA based Early Detection of Hepatocellular Carcinoma: a Feasibility Study with Preclinical Validation

Early detection of hepatocellular carcinoma (HCC) is critical for improving patient outcomes, yet current screening tools lack sensitivity and specificity. We demonstrate a flexible machine learning framework for HCC detection using methylation profiles from bisulfite sequencing across multiple assay platforms and sample types. The framework supports a “split-and-filter” approach that routes each ...

Intrinsic DNA sequence determinants and tissue-specific regulation of human replication origins

The accurate duplication of the genome relies on the spatiotemporal control of DNA replication initiation, yet the determinants specifying mammalian origin locations remain elusive. By developing ORIFormer, a transformer-based neural network, we decode a complex, conserved DNA sequence grammar that accurately predicts initiation sites. This approach uncovers novel determinants, which we validate b...

The expression level of CACNA1C-encoded CaV1.2 is a tipping point between promotion and inhibition of dendritic growth in neurons

The CACNA1C gene encodes the CaV1.2 L-type voltage-gated calcium channel, which plays a crucial role in neuronal signaling. CACNA1C is a risk gene for...

InfluenceNet: Encoding Motif Influence for Interpretable Modeling of Cis-Regulatory Syntax

Cis-regulatory elements shape gene expression by recruiting transcription factors (TFs) to DNA motifs, yet how motifs cooperate or compete across dist...

DTCFinder: a bench-to-bits toolkit for label-free, whole-spectrum analysis of disseminated and circulating tumor cells in liquid biopsies

Disseminated (DTCs) and circulating tumor cells (CTCs) are rare but pivotal in understanding cancer metastasis and advancing liquid biopsy-based diagn...

Genomic foundation models reveal RNA-binding proteins regulating translation and mRNA degradation during Drosophila development

The regulation of mRNA decay and translation is crucial for cellular function and development; however, the complex interplay of RNA-binding proteins ...

Programmatic design and editing of cis-regulatory elements

The development of modern genome editing and DNA synthesis has enabled researchers to edit DNA sequences with high precision but has left unsolved the...

scPRINT-2: Towards the next-generation of cell foundation models and benchmarks

Cell biology has been booming with foundation models trained on large single-cell RNA-seq databases, but benchmarks and capabilities remain unclear. W...

A Druggable Tumor Suppressor and Leukemic Stem Cell Marker

Acute myeloid leukemia (AML) often enters remission after chemotherapy but frequently relapses due to chemotherapy-resistant leukemic stem cells (LSCs...

CancerSTFormer enables multi-scale analysis of spot-resolution spatial transcriptomes and dissects gene and immune regulatory responses to targeted therapies

The growing number of spot-resolution sequencing based spatial transcriptomic (ST) datasets provides an unprecedented opportunity to study multicellul...

MicroGenomer: A Foundation Model for Transferable Microbial Genome Representations Enabling Multi-scale Genomic Understanding and Ecophysiological Trait Prediction

Microorganisms underpin global biogeochemical cycles and represent a vast, underexplored reservoir for sustainable biotechnology and human health. The...

A Biologically Grounded Structural Causal Model Enables cfRNA Specific In-Context Learning

Cell-free RNA (cfRNA) in human plasma provides a minimally invasive readout of tissue physiology, yet its extreme sparsity, heavy-tailed abundance dis...

A foundational model for joint sequence-function multi-species modeling at scale for long-range genomic prediction

Genomic prediction and design require models that integrate local sequence features with long-range regulatory dependencies spanning hundreds of kilob...

Integrative Genomic and Functional Analyses Reveal NINL as a Modulator of Tau Aggregation

Proteostasis dysfunction is a hallmark of frontotemporal dementia (FTD) and Alzheimer’s disease (AD), yet the genetic and molecular pathways that disr...

Interpretable Thermodynamic Score-based Classification of Relaxation Excursions

Classification and regression are cornerstones of computational biology and science at large, from identifying cell types to stratifying patients by d...

Identification of genomic features that uniquely impact estrogen receptor alpha binding and its effects on gene expression in endometrial cancer

Estrogen receptor alpha (ER) is an established oncogenic transcription factor in breast and endometrial cancer; however, more is known about the mecha...

vir2vec: A Viral Genome-Wide Viral Embedding

Genomic language models (gLMs) have recently emerged as powerful numerical surrogates for DNA, but existing architectures are largely focused on human...

Machine learning-based prediction of human structural variation and characterization of associated sequence determinants

Structural variants (SVs) represent a major source of genetic diversity and play key roles in human disease and evolution. Yet, the extent to which lo...

A Comparative Review of Deep Learning Methods for RNA Tertiary Structure Prediction

Several deep learning-based tools for RNA 3D structure prediction have recently emerged, including DRfold, DeepFoldRNA, RhoFold, RoseTTAFoldNA, trRose...

Ω-Loop mutations control dynamics of the active site by modulating the hydrogen-bonding network in PDC-3 β-lactamase

The expression of antibiotic-inactivating enzymes, such as Pseudomonas-derived cephalosporinase-3 (PDC-3), is a major mechanism of intrinsic resistanc...

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