title: Multilevel regularized regression for simultaneous taxa selection and network construction with metagenomic count data.
abstract: BACKGROUND
  Identifying disease associated taxa and constructing networks for bacteria interactions are two important tasks usually studied separately. In reality, differentiation of disease associated taxa and correlation among taxa may affect each other. One genus can be differentiated because it is highly correlated with another highly differentiated one. In addition, network structures may vary under different clinical conditions. Permutation tests are commonly used to detect differences between networks in distinct phenotypes, and they are time-consuming.
  
  
  RESULTS
  In this manuscript, we propose a multilevel regularized regression method to simultaneously identify taxa and construct networks. We also extend the framework to allow construction of a common network and differentiated network together. An efficient algorithm with dual formulation is developed to deal with the large-scale n ≪ m problem with a large number of taxa (m) and a small number of samples (n) efficiently. The proposed method is regularized with a general Lp (p ∈ [0, 2]) penalty and models the effects of taxa abundance differentiation and correlation jointly. We demonstrate that it can identify both true and biologically significant genera and network structures.
  
  
  METHODS
  Software MLRR in MATLAB is available at http://biostatistics.csmc.edu/mlrr/.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA, Molecular and Computational Biology Program, Department of Biological Sciences, USC, Los Angeles, CA 90089, USA, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA and F. Widjaja Foundation - Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Zhenqiu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA, Molecular and Computational Biology Program, Department of Biological Sciences, USC, Los Angeles, CA 90089, USA, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA and F. Widjaja Foundation - Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Fengzhu
authors.initials: F
authors.lastname: Sun
authors.affiliation: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA, Molecular and Computational Biology Program, Department of Biological Sciences, USC, Los Angeles, CA 90089, USA, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA and F. Widjaja Foundation - Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Braun
authors.affiliation: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA, Molecular and Computational Biology Program, Department of Biological Sciences, USC, Los Angeles, CA 90089, USA, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA and F. Widjaja Foundation - Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Dermot P B
authors.initials: DP
authors.lastname: McGovern
authors.affiliation: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA, Molecular and Computational Biology Program, Department of Biological Sciences, USC, Los Angeles, CA 90089, USA, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA and F. Widjaja Foundation - Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Piantadosi
mesh_terms: D000465:Algorithms; D001419:Bacteria / Q000145:classification* / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D056186:Metagenomics / Q000379:methods*; D010641:Phenotype; D012044:Regression Analysis; D012984:Software