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      LORSEN: Fast and Efficient eQTL Mapping With Low Rank Penalized Regression

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          Abstract

          Characterization of genetic variations that are associated with gene expression levels is essential to understand cellular mechanisms that underline human complex traits. Expression quantitative trait loci (eQTL) mapping attempts to identify genetic variants, such as single nucleotide polymorphisms (SNPs), that affect the expression of one or more genes. With the availability of a large volume of gene expression data, it is necessary and important to develop fast and efficient statistical and computational methods to perform eQTL mapping for such large scale data. In this paper, we proposed a new method, the low rank penalized regression method (LORSEN), for eQTL mapping. We evaluated and compared the performance of LORSEN with two existing methods for eQTL mapping using extensive simulations as well as real data from the HapMap3 project. Simulation studies showed that our method outperformed two commonly used methods for eQTL mapping, LORS and FastLORS, in many scenarios in terms of area under the curve (AUC). We illustrated the usefulness of our method by applying it to SNP variants data and gene expression levels on four chromosomes from the HapMap3 Project.

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          The meaning and use of the area under a receiver operating characteristic (ROC) curve.

          A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed ROC curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques.
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            Regression Shrinkage and Selection Via the Lasso

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              Regularization Paths for Generalized Linear Models via Coordinate Descent

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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                17 November 2021
                2021
                : 12
                : 690926
                Affiliations
                [ 1 ]Department of Mathematical Sciences, Michigan Technological University, Houghton, MI, United States
                [ 2 ]College of Forest Resources and Environmental Science, Michigan Technological University, Houghton, MI, United States
                Author notes

                Edited by: Qi Yan, Columbia University, United States

                Reviewed by: Rong Zhang, Amgen , United States

                Chi-Yang Chiu, University of Tennessee Health Science Center (UTHSC), United States

                *Correspondence: Kui Zhang, kuiz@ 123456mtu.edu

                This article was submitted to Statistical Genetics and Methodology, a section of the journal Frontiers in Genetics

                Article
                690926
                10.3389/fgene.2021.690926
                8636089
                4bd157b0-1a2f-42a7-b2b1-ad54c72adf90
                Copyright © 2021 Gao, Wei and Zhang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 April 2021
                : 08 October 2021
                Categories
                Genetics
                Methods

                Genetics
                eqtl mapping,proximal gradient method,cis-eqtl,trans-eqtl,penalized regression
                Genetics
                eqtl mapping, proximal gradient method, cis-eqtl, trans-eqtl, penalized regression

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