Calderon Munkholm (trainenemy04)
Single-cell RNA sequencing (scRNA-seq) captures whole transcriptome information of individual cells. While scRNA-seq measures thousands of genes, researchers are often interested in only dozens to hundreds of genes for a closer study. Then, a question is how to select those informative genes from scRNA-seq data. Moreover, single-cell targeted gene profiling technologies are gaining popularity for their low costs, high sensitivity and extra (e.g. spatial) information; however, they typically can only measure up to a few hundred genes. Then another challenging question is how to select genes for targeted gene profiling based on existing scRNA-seq data. Here, we develop the single-cell Projective Non-negative Matrix Factorization (scPNMF) method to select informative genes from scRNA-seq data in an unsupervised way. Compared with existing gene selection methods, scPNMF has two advantages. First, its selected informative genes can better distinguish cell types. Second, it enables the alignment of new targeted gene profiling data with reference data in a low-dimensional space to facilitate the prediction of cell types in the new data. Technically, scPNMF modifies the PNMF algorithm for gene selection by changing the initialization and adding a basis selection step, which selects informative bases to distinguish cell types. We demonstrate that scPNMF outperforms the state-of-the-art gene selection methods on diverse scRNA-seq datasets. selleck kinase inhibitor Moreover, we show that scPNMF can guide the design of targeted gene profiling experiments and the cell-type annotation on targeted gene profiling data. The R package is open-access and available at https//github.com/JSB-UCLA/scPNMF. The data used in this work are available at Zenodo https//doi.org/10.5281/zenodo.4797997. Supplementary data are available at Bioinformatics online. Supplementary data are available at Bioinformatics online. Tandem mass spectrometry data acquired using data independent acquisition (DIA) is challenging to interpret because the data exhibits complex structure along both the mass-to-charge (m/z) and time axes. The most common approach to analyzing this type of data makes use of a library of previously observed DIA data patterns (a 'spectral library'), but this approach is expensive because the libraries do not typically generalize well across laboratories. Here, we propose DIAmeter, a search engine that detects peptides in DIA data using only a peptide sequence database. Although some existing library-free DIA analysis methods (i) support data generated using both wide and narrow isolation windows, (ii) detect peptides containing post-translational modifications, (iii) analyze data from a variety of instrument platforms and (iv) are capable of detecting peptides even in the absence of detectable signal in the survey (MS1) scan, DIAmeter is the only method that offers all four capabilities in a single tool. The open source, Apache licensed source code is available as part of the Crux mass spectrometry analysis toolkit (http//crux.ms). Supplementary data are available at Bioinformatics online. Supplementary data are available at Bioinformatics online. Bacteriophages (aka phages), which mainly infect bacteria, play key roles in the biology of microbes. As the most abundant biological entities on the planet, the number of discovered phages is only the tip of the iceberg. Recently, many new phages have been revealed using high-throughput sequencing, particularly metagenomic sequencing. Compared to the fast accumulation of phage-like sequences, there is a serious lag in taxonomic classification of phages. High diversity, abundance and limited known phages pose great challenges for taxonomic analysis. In particular, alignment-based tools have difficulty in classifying fast accumulating contigs assembled from metagenomic data. In this work, we present