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.
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.
Epigenetic regulation involves the coordinated interplay of diverse proteins. We present COMBINE, a high-throughput platform that tests over 50,000 pairs of epigenetic effector domains up to 2,094 amino acids in length for their ability to modulate endogenous human gene transcription.
Here, we develop a multi-scale screening framework that integrates bulk patient transcriptomics, functional in vivo genetic screening, and single-cell transcriptomic and epigenomic profiling to nominate chromatin organizers that modulate ITH in breast cancer.
To identify strategies to enhance the utility of third-generation bi-steric mTORC1 inhibitors, we performed genome-scale CRISPR interference chemogenomics screens, which revealed that mTORC1 inhibitor-mediated cytostasis leaves cells exquisitely dependent on the lipid peroxide scavenging enzyme GPX4.
ENPP1 has long been linked with metabolic diseases, with the common ENPP1 K173Q variant conferring increased risk for type 2 diabetes. Here, we demonstrate that the K173Q variant has decreased cGAMP hydrolysis activity, suggesting that this loss of enzymatic function could contribute to its pathogenesis.