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The ability to predict scientific breakthroughs at scale would accelerate the pace of discovery and improve the efficiency of research investments. Recent advances in artificial intelligence, graph theory, and computing …

We used an autonomous lab, comprising a large language model (LLM) and a fully automated cloud laboratory, to optimize the cost efficiency of cell-free protein synthesis (CFPS). By conducting iterative optimization, the …

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The human basal ganglia (BG), subcortical nuclei fundamental to motor regulation and cognitive modulation, is constructed from neurons produced during gestation in the adjacent ganglionic eminences (GEs). GEs are transie…

The role of the immune system in regulating organismal lifespan remains poorly understood. Here, we show that CD4 T cells release "telomere Rivers" into circulation after acquiring telomeres from antigen-presenting cells…

MotivationThe rational design of chemical compounds that bind to a desired protein target molecule is a major goal of drug discovery. Most current molecular docking but also fragment-based build-up or machine-learning ba…

The ubiquitous availability of protein structures permits replacing sequence alignment with more accurate and sensitive structure alignment algorithms. LoL-align maximizes a local log-odds score for proteins to be homolo…

Constructing a cell universe requires integrating heterogeneous single-cell RNA-seq datasets, but is hindered by diverse batch effects. Single-cell foundation models (scFMs), inspired by large language models, aim to lea…

Understanding how genomic sequences shape three-dimensional (3D) genome architecture is funda-mental to interpreting diverse biological processes. Although previous studies have shown that sequence information can predic…

BackgroundSomatic mutations are increasingly recognised as drivers of diseases beyond cancer, including autoimmune disorders. However, identifying rare, cell type-specific causal mutations remains challenging due to thei…

Cell biology has been booming with foundation models trained on large single-cell RNA-seq databases, but benchmarks and capabilities remain unclear. We propose an additive benchmark across a gymnasium of tasks to discove…

Annotating single-cell and spatial RNA-seq data can be greatly enhanced by leveraging bulk RNA-seq, which remains a cost-effective and well-established benchmark for characterising transcriptional activity in immune cell…

Remarkable progress has been achieved by machine learning, particularly in accurate prediction of protein tertiary structures. Despite these advances, accurately annotating protein functions through machine learning appr…

MotivationMultiomics data integration aims to identify biological patterns shared across different molecular modalities. Traditional methods focus on detecting either jointly shared variation (across all modalities) or i…

Recent advances in spatially-resolved transcriptomics have enabled profiling of gene expression in a spatial context, which has led to the generation of large-scale single-cell and spatial atlases with computationally-de…

AO_SCPLOWBSTRACTC_SCPLOWProtein-language models (pLMs) provide a novel means for mapping the protein space. Which of these new maps best advances specific biological analyses, however, is not obvious. To elucidate the pr…

Proteins are essential in biological processes, primarily through their interactions with other molecules, including proteins. These interactions are crucial for cellular functions and maintaining life. Predicting Protei…

IntroductionChromatin accessibility profiling is an important tool for understanding gene regulation and cellular function. While public repositories house nearly 10,000 scATAC-seq experiments, unifying this data for mea…

The increasing size of single-cell RNA sequencing (scRNA-seq) datasets poses major computational challenges. This work benchmarks the scalability, efficiency, and accuracy of five widely used analysis frameworks (Seurat,…

RNA velocity is a computational framework for single-cell RNA sequencing (scRNA-seq) that estimates the future transcriptional state of individual cells, thereby capturing the direction and rate of cell state transitions…

Biosynthetic gene clusters (BGCs) are contiguous genomic regions that encode diverse, non-homologous proteins required for the production of specific natural products. Their genetic diversity underlies the structural com…

Single-cell and spatial transcriptomics have generated vast atlases of cellular states, yet these data are almost exclusively used for analysis rather than generation. Here we introduce the LLM-based model PGL, Portrayin…

Defining all human cell types and their roles in health and disease is a central goal of biology. Single-cell RNA sequencing has enabled the construction of organ-specific cell atlases, but building a comprehensive organ…

Perturbational studies are the gold standard for identifying causal relationships between components of biological systems. Recent technological advances, including Perturb-seq and related assays, have enabled high-throu…

Genomic language models (gLMs) have recently emerged as powerful numerical surrogates for DNA, but existing architectures are largely focused on human DNA or trained on limited viral references, and no dedicated benchmar…

1Single cells interact continuously to form a cell environment that drives key biological processes. Cells and cell environments are highly dynamic across time and space, fundamentally governed by molecular mechanisms, s…

Gene knockout experiments are essential for dissecting gene function, and CRISPR has made targeted gene disruption more accessible than ever. Single-cell CRISPR screening enables the construction of rich genetic perturba…

The FASTQ file format is the lingua franca of primary data distribution and processing across most of bioinformatics. Over time, the compression, storage, transmission, and decompression of gzip compressed fastq.gz files…

Human height can be divided into sitting height and leg length, reflecting growth of different parts of the skeleton whose relative proportions are captured by the ratio of sitting to total height (as sitting height rati…

The HXB/BXH family of recombinant inbred rat strains is a unique genetic resource that has been extensively phenotyped over 25 years, resulting in a vast dataset of quantitative molecular and physiological phenotypes. We…

Single-cell RNA sequencing datasets comprise true single cells, or singlets, in addition to cells that coalesce during the protocol, or doublets. Identifying singlets with high fidelity in single-cell RNA sequencing is n…

Yeast, a single eukaryotic cell model organism, demonstrates a progressive aging process. In the era of synthetic biology, study of the impact of synthetic chromosomes and aging is urgent and intriguing. Herein, we succe…

Insulinomas are rare neuroendocrine tumours arising from the pancreatic {beta}-cells. While retaining the ability to produce insulin, insulinomas feature aberrant proliferation and altered hormone secretion resulting in …

The development of Spatially Resolved Transcriptomics (SRT) technologies has revolutionized the study of tissue organization. We introduce a graph convolutional network with an attention and positive emphasis mechanism, …

In recent years, high-throughput spatial transcriptomics has emerged as a powerful tool for investigating the spatial distribution of mRNA expression and the effects it may have on cellular function. There is a lack of s…

The human genome is dominated by noncoding sequences, most of which are poorly conserved across species. How genetic information is distributed between coding and noncoding regions remains a fundamental unresolved questi…

Hybridization-based spatial transcriptomics technologies have advanced our ability to map cellular and subcellular organization in complex tissues. However, existing methods remain constrained in gene coverage, multimoda…

Biological aging imposes significant socio-economic costs, increasing health expenses, reducing productivity, stalling population growth and straining social systems, culminating in reduced economic activity. We draw ins…

We introduce Protenix-v1 (PX-v1), the first open-source structure prediction model to attain superior performance to AlphaFold3 while strictly adhering to the same training data cutoff, model size, and inference budget. …

Lipid nanoparticles (LNPs) are established carriers for nucleic acid delivery, however, achieving efficient delivery to non-hepatic tissues remains a major challenge. Here, we present LipiGo, a nanocarrier platform engin…

The identity of a cell is governed by regulatory proteins binding to the genome to control gene expression. Mapping these genome-wide binding events across thousands of proteins and cell types is essential for understand…

Therapeutic peptides combine the advantages of small molecules and antibodies, offering target flexibility and low immunogenicity, yet their successful translation requires careful evaluation of multiple developability p…

The detection of low-biomass microbial DNA in human tissues is often confounded by contamination, as demonstrated in the debates over the existence of microbiomes in the placenta, brain, blood, and tumors. Here we show t…