Sparse reduced-rank regression for integrating omics data

Background The problem of assessing associations between multiple omics data including genomics and metabolomics data to identify biomarkers potentially predictive of complex diseases has garnered considerable research interest nowadays. A popular epidemiology approach is to consider an association of each of the predictors with each of the response using a univariate linear regression model, and to select predictors that meet a priori specified significance level. Although this approach is simple and intuitive, it tends to require larger sample size which is costly. It also assumes variables for each data type are independent, and thus ignores correlations that exist between variables both within each data type and across the data types. Results We consider a multivariate linear regression model that relates multiple predictors with multiple responses, and to identify multiple relevant predictors that are simultaneously associated with the responses. We assume the coefficient matrix of the responses on the predictors is both row-sparse and of low-rank, and propose a group Dantzig type formulation to estimate the coefficient matrix. Conclusion Extensive simulations demonstrate the competitive performance of our proposed method when compared to existing methods in terms of estimation, prediction, and variable selection. We use the proposed method to integrate genomics and metabolomics data to identify genetic variants that are potentially predictive of atherosclerosis cardiovascular disease (ASCVD) beyond well-established risk factors. Our analysis shows some genetic variants that increase prediction of ASCVD beyond some well-established factors of ASCVD, and also suggest a potential utility of the identified genetic variants in explaining possible association between certain metabolites and ASCVD.

[1]  M. Wegkamp,et al.  Optimal selection of reduced rank estimators of high-dimensional matrices , 2010, 1004.2995.

[2]  G. Reinsel,et al.  Multivariate Reduced-Rank Regression: Theory and Applications , 1998 .

[3]  G. Limongelli,et al.  Inflammation and Cardiovascular Disease: From Pathogenesis to Therapeutic Target , 2014, Current Atherosclerosis Reports.

[4]  Alan Julian Izenman,et al.  Modern Multivariate Statistical Techniques , 2008 .

[5]  Fabian J Theis,et al.  Computational approaches for systems metabolomics. , 2016, Current opinion in biotechnology.

[6]  Stephen P. Boyd,et al.  Graph Implementations for Nonsmooth Convex Programs , 2008, Recent Advances in Learning and Control.

[7]  Zhuang Ma,et al.  Adaptive Estimation in Two-way Sparse Reduced-rank Regression , 2014, 1403.1922.

[8]  Xin Qi,et al.  Signal extraction approach for sparse multivariate response regression , 2017, J. Multivar. Anal..

[9]  Y. She,et al.  Selective Factor Extraction in High Dimensions , 2014, 1403.6212.

[10]  J. Griffin The Cinderella story of metabolic profiling: does metabolomics get to go to the functional genomics ball? , 2006, Philosophical Transactions of the Royal Society B: Biological Sciences.

[11]  P. Stenvinkel,et al.  Plasma sulfur amino acids in relation to cardiovascular disease, nutritional status, and diabetes mellitus in patients with chronic renal failure at start of dialysis therapy. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[12]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[13]  A. Tsybakov,et al.  Estimation of high-dimensional low-rank matrices , 2009, 0912.5338.

[14]  Jennifer G. Robinson,et al.  Reply: 2013 ACC/AHA guideline on the assessment of cardiovascular risk. , 2014, Journal of the American College of Cardiology.

[15]  Ji Zhu,et al.  Regularized Multivariate Regression for Identifying Master Predictors with Application to Integrative Genomics Study of Breast Cancer. , 2008, The annals of applied statistics.

[16]  Martin J. Wainwright,et al.  Estimation of (near) low-rank matrices with noise and high-dimensional scaling , 2009, ICML.

[17]  Alan Julian Izenman,et al.  Modern Multivariate Statistical Techniques: Regression, Classification, and Manifold Learning , 2008 .

[18]  R. Tibshirani,et al.  Efficient quadratic regularization for expression arrays. , 2004, Biostatistics.

[19]  M. Yuan,et al.  Dimension reduction and coefficient estimation in multivariate linear regression , 2007 .

[20]  R. Vasan,et al.  Genetic Architecture of the Cardiovascular Risk Proteome , 2017, Circulation.

[21]  P. Tontonoz,et al.  PPARs in atherosclerosis: the clot thickens. , 2004, The Journal of clinical investigation.

[22]  M. Wegkamp,et al.  Joint variable and rank selection for parsimonious estimation of high-dimensional matrices , 2011, 1110.3556.

[23]  Jennifer G. Robinson,et al.  2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines , 2014, Circulation.

[24]  Xiang Gao,et al.  Association of sulfur amino acid consumption with cardiometabolic risk factors: Cross-sectional findings from NHANES III , 2020, EClinicalMedicine.

[25]  Joanna M. Young,et al.  Inflammatory biomarkers for predicting cardiovascular disease. , 2013, Clinical biochemistry.

[26]  Y. She,et al.  Robust reduced-rank regression , 2015, Biometrika.

[27]  Hilde van der Togt,et al.  Publisher's Note , 2003, J. Netw. Comput. Appl..

[28]  Terence Tao,et al.  The Dantzig selector: Statistical estimation when P is much larger than n , 2005, math/0506081.

[29]  Kung-Sik Chan,et al.  Reduced rank stochastic regression with a sparse singular value decomposition , 2012 .

[30]  S. Keleş,et al.  Sparse partial least squares regression for simultaneous dimension reduction and variable selection , 2010, Journal of the Royal Statistical Society. Series B, Statistical methodology.

[31]  N. Stone Preventing Atherosclerotic Cardiovascular Disease Using American College of Cardiology and American Heart Association Prevention Guidelines: Some Good News, But Caveats Remain , 2016, Journal of the American Heart Association.

[32]  Jennifer G. Robinson,et al.  2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines , 2014, Circulation.

[33]  Jianhua Z. Huang,et al.  Sparse Reduced-Rank Regression for Simultaneous Dimension Reduction and Variable Selection , 2012 .

[34]  Christian Gieger,et al.  Genetics Meets Metabolomics: A Genome-Wide Association Study of Metabolite Profiles in Human Serum , 2008, PLoS genetics.

[35]  Kung-Sik Chan,et al.  Reduced rank regression via adaptive nuclear norm penalization. , 2012, Biometrika.

[36]  Emmanuel J. Candès,et al.  Tight Oracle Inequalities for Low-Rank Matrix Recovery From a Minimal Number of Noisy Random Measurements , 2011, IEEE Transactions on Information Theory.

[37]  Dylan S. Small,et al.  A review of instrumental variable estimators for Mendelian randomization , 2015, Statistical methods in medical research.

[38]  M. Wegkamp,et al.  Adaptive estimation of the rank of the coefficient matrix in high-dimensional multivariate response regression models , 2017, The Annals of Statistics.

[39]  A. Khera,et al.  Genetics of coronary artery disease: discovery, biology and clinical translation , 2017, Nature Reviews Genetics.

[40]  P. Deedwania Metabolic syndrome and vascular disease: is nature or nurture leading the new epidemic of cardiovascular disease? , 2003, Circulation.

[41]  Markus Perola,et al.  Genome-wide association study identifies multiple loci influencing human serum metabolite levels , 2012, Nature Genetics.

[42]  Emmanuel J. Candès,et al.  Tight oracle bounds for low-rank matrix recovery from a minimal number of random measurements , 2010, ArXiv.

[43]  Paul M. Ridker,et al.  Inflammation as a Cardiovascular Risk Factor , 2004, Circulation.

[44]  D. Wilcken,et al.  The pathogenesis of coronary artery disease. A possible role for methionine metabolism. , 1976, The Journal of clinical investigation.

[45]  C. Newgard,et al.  Integrated metabolomics and genomics: systems approaches to biomarkers and mechanisms of cardiovascular disease. , 2015, Circulation. Cardiovascular genetics.

[46]  Shane J. Neph,et al.  Systematic Localization of Common Disease-Associated Variation in Regulatory DNA , 2012, Science.