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Using an experimental and computational framework inspired by compressed sensing, we greatly reduced the number of measurements needed to run Perturb-seq. Our compressed Perturb-seq strategy relies on collecting measurements comprising random linear combinations of genetic perturbations, followed by deconvolving the perturbation effects on the transcriptome using sparsity-exploiting algorithms.
We designed a method for fast aptamer selection by integrating biomaterials science, engineering principles and biology. Aptamer candidates dynamically interacting with immobilized targets in a three-dimensional, non-fouling and macroporous polyethylene glycol hydrogel were rapidly enriched and selected with high affinity against five protein targets.
Most features of a cell are determined by gene programs — sets of co-expressed genes that execute a specific function. By incorporating existing knowledge about gene programs and cell types, the Spectra factor analysis method improves how we decode single-cell transcriptomic data and offers insights into challenging tumor immune contexts.
The detection of mobile genetic elements is crucial for exploring the ecology and evolution of microbial communities, and it has diverse implications in biotechnology and public health. geNomad is a computational framework that enables researchers to precisely identifiy and annotate plasmids and viruses in sequencing data on a large scale.
By using fixed charges to engineer a strong electroosmotic flow, we achieve the unidirectional transport of natural polypeptides across nanopores. Our approach enables native proteins to be transported enzymatically and non-enzymatically in the absence of denaturant and electrophoretic tags, with potential applications for protein sequencing.
BugSigDB is a community-editable wiki that harmonizes how key microbial differential abundance methods and results are reported, identifying rare and common patterns across the literature of published host-associated microbiome studies.
Data integration between weakly linked single-cell modalities is challenging using existing methods. Therefore, we developed MaxFuse to enable matching and integration between cells from modalities such as single-cell spatial proteomic datasets and single-cell transcriptomic datasets, or other modalities where features are only weakly correlated.
Although base and prime editors can be highly efficient in human hematopoietic stem cells, we find they can cause adverse cellular responses, including reduced engraftment and the generation of DNA double-strand breaks and genotoxic byproducts, albeit at a lower frequency than Cas9. We also find that base editors increase the genome-wide mutagenic load.
Human glial progenitors transplanted into a chimeric mouse brain replace sick or older human glia, a finding that could one day lead to new treatments for neurological disease.
GEARS, a machine learning model informed by biological knowledge of gene–gene relationships, effectively predicts transcriptional responses to multi-gene perturbations. GEARS can predict the effects of perturbing previously unperturbed genes and detects non-additive interactions, such as synergy, when predicting combinatorial perturbation outcomes. Thus, GEARS expands insights gained from perturbational screens.
Directly analyzing the role of the gut microbiota during the course of infection with human-specific pathogens is not possible with existing methods. To overcome this problem, we developed a germ-free precision mouse model, which we used to compare the acquisition, replication and pathogenesis of HIV and Epstein–Barr virus.
A systematic examination of eight different single-cell assay for transposase-accessible chromatin by sequencing (scATAC-seq) technologies revealed marked differences in the complexity of sequencing libraries and the specificity of DNA tagmentation that they achieve. Our pipeline for universal mapping of scATAC-seq data (PUMATAC) allowed a fair benchmarking of existing methods and enables the seamless integration of future datasets and technologies.