title: Meta-analytic framework for sparseK-means to identify disease subtypes in multiple transcriptomic studies.
abstract: Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparseK-means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups.
authors.affiliation: Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15261, zhh18@pitt.edu.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Huo
authors.affiliation: Department of Computational Biology, University of Pittsburgh, Pittsburgh, PA 15261, dingying85@gmail.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Computational Biology, University of Pittsburgh, Pittsburgh, PA 15261, shl96@pitt.edu.
authors.forename: Silvia
authors.initials: S
authors.lastname: Liu
authors.affiliation: Magee-Womens Research Institute, Pittsburgh, PA 15213, oesterreichs@upmc.edu.
authors.forename: Steffi
authors.initials: S
authors.lastname: Oesterreich
authors.affiliation: Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15261, ctseng@pitt.edu.
authors.forename: George
authors.initials: G
authors.lastname: Tseng
keywords: Disease subtype discovery; K-means; Lasso; Meta-analysis; Unsupervised machine learning