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      dRFEtools: dynamic recursive feature elimination for omics

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      , ,
      Bioinformatics
      Oxford University Press

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          Abstract

          Motivation

          Advances in technology have generated larger omics datasets with potential applications for machine learning. In many datasets, however, cost and limited sample availability result in an excessively higher number of features as compared to observations. Moreover, biological processes are associated with networks of core and peripheral genes, while traditional feature selection approaches capture only core genes.

          Results

          To overcome these limitations, we present dRFEtools that implements dynamic recursive feature elimination (RFE), reducing computational time with high accuracy compared to standard RFE, expanding dynamic RFE to regression algorithms, and outputting the subsets of features that hold predictive power with and without peripheral features. dRFEtools integrates with scikit-learn (the popular Python machine learning platform) and thus provides new opportunities for dynamic RFE in large-scale omics data while enhancing its interpretability.

          Availability and implementation

          dRFEtools is freely available on PyPI at https://pypi.org/project/drfetools/ or on GitHub https://github.com/LieberInstitute/dRFEtools, implemented in Python 3, and supported on Linux, Windows, and Mac OS.

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          Most cited references5

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          An Expanded View of Complex Traits: From Polygenic to Omnigenic

          A central goal of genetics is to understand the links between genetic variation and disease. Intuitively, one might expect disease-causing variants to cluster into key pathways that drive disease etiology. But for complex traits, association signals tend to be spread across most of the genome-including near many genes without an obvious connection to disease. We propose that gene regulatory networks are sufficiently interconnected such that all genes expressed in disease-relevant cells are liable to affect the functions of core disease-related genes and that most heritability can be explained by effects on genes outside core pathways. We refer to this hypothesis as an "omnigenic" model.
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            Developmental and genetic regulation of the human cortex transcriptome illuminate schizophrenia pathogenesis

            Summary: GWAS have identified 108 schizophrenia risk loci, but risk mechanisms for individual loci are largely unknown. Using developmental, genetic, and illness-based RNA sequencing expression analysis in human brain, we characterized the human brain transcriptome around these loci and found enrichment for developmentally regulated genes with novel examples of shifting isoform usage across pre- and post-natal life. Across the genome, we found widespread expression quantitative trait loci (eQTLs), including many with transcript specificity and previously unannotated sequence that were independently replicated. We leveraged this general eQTL database to show that 48.1% of risk variants for schizophrenia associated with nearby expression. We lastly found 237 genes significantly differentially expressed between patients and controls which replicated in an independent dataset, implicated synaptic processes and were strongly regulated in early development. These findings together offer genetic- and diagnosis-related targets for better modeling schizophrenia risk. This publicly-available resource is available at: http://eqtl.brainseq.org/phase1
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              Regional Heterogeneity in Gene Expression, Regulation, and Coherence in the Frontal Cortex and Hippocampus across Development and Schizophrenia

              The hippocampus formation, although prominently implicated in schizophrenia pathogenesis, has been overlooked in large-scale genomics efforts in the schizophrenic brain. We performed RNA-seq in hippocampi and dorsolateral prefrontal cortices (DLPFCs) from 551 individuals (286 with schizophrenia). We identified substantial regional differences in gene expression and found widespread developmental differences that were independent of cellular composition. We identified 48 and 245 differentially expressed genes (DEGs) associated with schizophrenia within the hippocampus and DLPFC, with little overlap between the brain regions. 124 of 163 (76.6%) of schizophrenia GWAS risk loci contained eQTLs in any region. Transcriptome-wide association studies in each region identified many novel schizophrenia risk features that were brain region-specific. Last, we identified potential molecular correlates of in vivo evidence of altered prefrontal-hippocampal functional coherence in schizophrenia. These results underscore the complexity and regional heterogeneity of the transcriptional correlates of schizophrenia and offer new insights into potentially causative biology. Collado-Torres et al. describe the BrainSeq Phase II gene expression resource encompassing two brain regions from 551 genotyped individuals spanning the entire human lifespan (286 with schizophrenia). This resource can answer region-specific questions about development and schizophrenia and its genetic risk.
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                Author and article information

                Contributors
                Role: Associate Editor
                Journal
                Bioinformatics
                Bioinformatics
                bioinformatics
                Bioinformatics
                Oxford University Press
                1367-4803
                1367-4811
                August 2023
                26 August 2023
                26 August 2023
                : 39
                : 8
                : btad513
                Affiliations
                Lieber Institute for Brain Development , Baltimore, MD 21205, United States
                Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, MD 21205, United States
                Lieber Institute for Brain Development , Baltimore, MD 21205, United States
                Lieber Institute for Brain Development , Baltimore, MD 21205, United States
                Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, MD 21205, United States
                Author notes
                Corresponding authors. Lieber Institute for Brain Development, 855 N Wolfe St, #300, Baltimore, MD 21205, United States. E-mails: kynonjade.benjamin@ 123456libd.org (K.J.M.B.) and apua.paquola@ 123456libd.org (A.C.M.P.)
                Author information
                https://orcid.org/0000-0003-2016-4646
                Article
                btad513
                10.1093/bioinformatics/btad513
                10471895
                37632789
                b334d5f8-4e6a-4687-8cf9-725560d49cec
                © The Author(s) 2023. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 November 2022
                : 09 July 2023
                : 16 August 2023
                : 31 August 2023
                Page count
                Pages: 3
                Funding
                Funded by: National Institute on Minority Health;
                Funded by: Health Disparities of the National Institutes of Health;
                Award ID: K99MD016964
                Categories
                Applications Note
                Genome Analysis
                AcademicSubjects/SCI01060

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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