JMASM 52: Extremely Efficient Permutation and Bootstrap Hypothesis Tests Using R

Re-sampling based statistical tests are known to be computationally heavy, but reliable when small sample sizes are available. Despite their nice theoretical properties not much effort has been put to make them efficient. Computationally efficient method for calculating permutation-based p-values for the Pearson correlation coefficient and two independent samples t-test are proposed. The method is general and can be applied to other similar two sample mean or two mean vectors cases

Enhanced protein isoform characterization through long-read proteogenomics

[Background] The detection of physiologically relevant protein isoforms encoded by the human genome is critical to biomedicine. Mass spectrometry (MS)-based proteomics is the preeminent method for protein detection, but isoform-resolved proteomic analysis relies on accurate reference databases that match the sample; neither a subset nor a superset database is ideal. Long-read RNA sequencing (e.g., PacBio or Oxford Nanopore) provides full-length transcripts which can be used to predict full-length protein isoforms.[Results] We describe here a long-read proteogenomics approach for integrating sample-matched long-read RNA-seq and MS-based proteomics data to enhance isoform characterization. We introduce a classification scheme for protein isoforms, discover novel protein isoforms, and present the first protein inference algorithm for the direct incorporation of long-read transcriptome data to enable detection of protein isoforms previously intractable to MS-based detection. We have released an open-source Nextflow pipeline that integrates long-read sequencing in a proteomic workflow for isoform-resolved analysis.[Conclusions] Our work suggests that the incorporation of long-read sequencing and proteomic data can facilitate improved characterization of human protein isoform diversity. Our first-generation pipeline provides a strong foundation for future development of long-read proteogenomics and its adoption for both basic and translational research.This work was supported by a National Institutes of Health (NIH) grant R35GM142647 (G.M.S.), NIH grant R35GM126914 (L.M.S.), and Jackson Laboratory (A.D.M.). The codeathon which initiated the project was supported by the NIH STRIDES Initiative at the NIH.Peer reviewe