Ultra-high efficiency T cell reprogramming at multiple loci with SEED-Selection.

Multiplexed reprogramming of T cell specificity and function can generate powerful next-generation cellular therapies. However, current manufacturing methods produce heterogenous mixtures of partially engineered cells. Here, we develop a one-step process to enrich for unlabeled cells with knock-ins at multiple target loci using a family of repair templates named Synthetic Exon/Expression Disruptors (SEEDs).

Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement.

Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816).

Genome-wide prediction of disease variant effects with a deep protein language model.

Predicting the effects of coding variants is a major challenge. While recent deep-learning models have improved variant effect prediction accuracy, they cannot analyze all coding variants due to dependency on close homologs or software limitations. Here we developed a workflow using ESM1b, a 650-million-parameter protein language model, to predict all ~450 million possible missense variant effects in the human genome, and made all predictions available on a web portal.

Characterizing changes in soil microbiome abundance and diversity due to different cover crop techniques.

Soil-based microorganisms assume a direct and crucial role in the promotion of soil health, quality and fertility, all factors known to contribute heavily to the quality and yield of agricultural products. Cover cropping, used in both traditional and organic farming, is a particularly efficient and environmentally favorable tool for manipulating microbiome composition in agricultural soils and has had clear benefits for soil quality and crop output. Several long-term investigations have evaluated the influence of multi-mix (multiple species) cover crop treatments on soil health and microbial diversity.