Changes in gene expression have been observed in the aging human brain, but our understanding of the underlying regulatory mechanisms remains limited. We analyzed single-nucleus gene expression, chromatin accessibility, DNA methylation, and 3D chromatin architecture from human hippocampal tissues spanning the adult lifespan.
Many diseases are linked to defects in Complex I subunits, but the extent to which non-mitochondrial proteins contribute to CI function is less clear. Here, we perform CRISPR screens to identify regulators of CI abundance across its N, Q, and P modules, which mediate NADH oxidation, quinone reduction, and proton pumping, respectively.
Impaired mitochondrial proteostasis underlies a broad spectrum of diseases, yet effective therapies remain limited. Here we show that deficiency of HTRA2, a mitochondrial intermembrane space protease, can be rescued by hypoxia therapy.
Programmable composition of complex systems is a longstanding goal of biological research. Generative modeling has improved the reliability of computational design, but existing methods are highly specialized and are difficult to extend or compose. Here, we introduce Proto, a high-level programming language for generative biology.
Obtaining antibodies to specific protein targets is a widely important yet experimentally laborious process. Here we introduce Germinal, a broadly enabling generative pipeline that designs antibodies against specific epitopes with nanomolar binding affinities while requiring only low-n experimental testing.
STING agonists are promising innate immune therapies, but their effectiveness is limited by the toxicity to activated T cells. Here, we identify the cationic amino acid transporter SLC7A1 as a cGAMP transporter and suggest that modulation of SLC7A1 may influence T cell susceptibility to cGAMP and its analogs.
Modern genomics produces billions of sequencing records per run, which are typically stored as gzip-compressed FASTQ files. While this format is widely used, it is not optimal for high-throughput processing. Here, we present BINSEQ, a family of simple binary formats that enable high-throughput parallel processing of sequencing data.
We developed PerturbSpace, a novel approach that integrates CRISPR perturbations with spatially hashed single-cell multiomics. This approach enables the first high-throughput, spatially resolved Perturb-seq analysis across complex tissue architecture in vivo.
Here, we present Iteratively Defined Lengths of Inaccessibility (IDLI), a computational method that maps the single-molecule co-occupancy of structurally distinct nucleosomes, subnucleosomes and other protein–DNA interactions through long-read single-molecule footprinting.
Delivering mRNA to specific cell types remains challenging. Recent work opens the possibility of using synthetic RNA transfer pathways to engineer mRNA ‘delivery cells’. These cells could enable targeted editing, reprogramming or elimination of selected cells for therapeutic benefit.