title: Identification of Reliable Components in Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS): a Data-Driven Approach across Metabolic Processes.
abstract: There is an increasing need to use multivariate statistical methods for understanding biological functions, identifying the mechanisms of diseases, and exploring biomarkers. In addition to classical analyses such as hierarchical cluster analysis, principal component analysis, and partial least squares discriminant analysis, various multivariate strategies, including independent component analysis, non-negative matrix factorization, and multivariate curve resolution, have recently been proposed. However, determining the number of components is problematic. Despite the proposal of several different methods, no satisfactory approach has yet been reported. To resolve this problem, we implemented a new idea: classifying a component as "reliable" or "unreliable" based on the reproducibility of its appearance, regardless of the number of components in the calculation. Using the clustering method for classification, we applied this idea to multivariate curve resolution-alternating least squares (MCR-ALS). Comparisons between conventional and modified methods applied to proton nuclear magnetic resonance ((1)H-NMR) spectral datasets derived from known standard mixtures and biological mixtures (urine and feces of mice) revealed that more plausible results are obtained by the modified method. In particular, clusters containing little information were detected with reliability. This strategy, named "cluster-aided MCR-ALS," will facilitate the attainment of more reliable results in the metabolomics datasets.
authors.affiliation: Team for Advanced Development and Evaluation of Human Disease Models, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Motegi
authors.affiliation: RIKEN Center for Sustainable Resource Science, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Yuuri
authors.initials: Y
authors.lastname: Tsuboi
authors.affiliation: Team for Advanced Development and Evaluation of Human Disease Models, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Saga
authors.affiliation: Team for Advanced Development and Evaluation of Human Disease Models, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kagami
authors.affiliation: Team for Advanced Development and Evaluation of Human Disease Models, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Team for Advanced Development and Evaluation of Human Disease Models, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Toki
authors.affiliation: Team for Advanced Development and Evaluation of Human Disease Models, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Minowa
authors.affiliation: Team for Advanced Development and Evaluation of Human Disease Models, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.|Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research (JFCR), 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
authors.affiliation: RIKEN Center for Sustainable Resource Science, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|Graduate School of Bioagricultural Sciences, Nagoya University, 1 Furo-cho, Chikusa-ku, Nagoya, Aichi 464-0810, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kikuchi
mesh_terms: D000465:Algorithms; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D016000:Cluster Analysis; D003627:Data Interpretation, Statistical; D016002:Discriminant Analysis; D005243:Feces / Q000737:chemistry*; D016018:Least-Squares Analysis; D055432:Metabolomics / Q000379:methods / Q000706:statistics & numerical data; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015999:Multivariate Analysis; D025341:Principal Component Analysis / Q000379:methods*; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D015203:Reproducibility of Results; D014556:Urine / Q000737:chemistry*
chemical_list: D015415:Biomarkers