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Challenges in somatic variant calling include a lack of long-read variant callers and of publicly available benchmarking datasets. We developed DeepSomatic, a somatic variant caller for short- and long-read technologies, and created seven somatic variant benchmarks derived from cancer cell lines, which we make available as a public database: CASTLE-panel.
Precise control of transgene expression remains a challenge in engineering primary cells for diverse applications. We developed DIAL, a promoter editing framework that transmits transient inputs into stable setpoints of expression in primary cells and human induced pluripotent stem cells, paving the way for predictable programming of gene circuits in therapeutically relevant cells.
A method to produce embryonic stem cells for a range of bird species opens up opportunities in agriculture, developmental biology and species conservation.
Most bacteria cannot be grown in the laboratory, which means that their genetic diversity is hidden to traditional culture-based studies. We combined a new DNA extraction method, long-read sequencing, bioinformatics and chemical synthesis to access the genetic diversity of uncultured soil bacteria and abiotically decode it to discover bioactive small molecules.
A new screen platform named DEFUSE (DEath FUSion Escape) enables high-throughput discovery of small molecule protein degraders. DEFUSE identified SKPer1, a molecule that works by inducing proximity between an oncogenic driver and an E3 ligase, opening new avenues for targeted protein degradation.
Antibody–drug conjugates (ADCs) are promising targeted cancer therapies but have a limited payload scope. Antibody–bottlebrush prodrug conjugates offer modular synthesis and high drug-to-antibody ratios, enabling the use of a broad range of payloads, including lower potency drugs, while performing favorably compared to traditional ADCs in preclinical models.
We developed a universal control system and multitarget optimization framework that enables dynamic and synchronized expression of multiple genes and facilitates the overproduction of specific secondary metabolites in Streptomyces species.
Precision CRISPR–Cas9-mediated genome engineering remains challenging, particularly gene integration and editing in non-dividing cells. We present Pythia, a deep learning solution that forecasts optimal repair templates and enables predictable and accurate genome editing in diverse cellular contexts, both in vivo and in vitro.
A robust, clinically tractable skin metatranscriptomics workflow provides high technical reproducibility of profiles, uniform coverage across genes, and strong enrichment of microbial messenger RNAs across different skin sites. This workflow is useful for identifying active species and microbial functions in vivo for future biomarker discovery.
PepMLM, a protein language model fine-tuned on protein–peptide data, can generate potent, target-specific linear peptides capable of binding to and degrading proteins ranging from cancer receptors to drivers of neurodegeneration and viral proteins, all without requiring protein structural information.
Recent developments in B cell engineering expand our ability to study human disease and drive progress toward new B cell therapies, balancing challenges in clinical implementation with emerging opportunities.
Cells in a tissue influence each other through physical and chemical cues as they differentiate to their final fates and migrate through space. A new technique integrates spatial transcriptomic data with the dynamics of RNA transcription and splicing across an entire tissue to model the directions of cell differentiation and migration.
We developed low-input multiple methylation sequencing (LIME-seq) to detect RNA modifications in plasma cell-free RNA (cfRNA) and identified microbiome-derived RNA modification signatures that can distinguish people with colorectal cancer from those without. We suggest that monitoring the modification levels on cfRNA or other RNA species could aid disease diagnosis and prognosis.
Gene regulatory networks are crucial for understanding complex gene regulation in plants and could advance crop improvement for more sustainable and climate-resilient agricultural practices.
