Xinyan Zhang1, Bingzong Li2, Huiying Han3, Sha Song3, Hongxia Xu3, Zixuan Yi4, Yating Hong2, Wenzhuo Zhuang3, Nengjun Yi5. 1. Department of Biostatistics, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA, USA. 2. Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, China. 3. Department of Cell Biology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China. 4. School of Medicine, Eastern Virginia Medical School, Norfork, VA, USA. 5. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
Abstract
Motivation: Molecular analyses suggest that myeloma is composed of distinct sub-types that have different molecular pathologies and various response rates to certain treatments. Drug responses in multiple myeloma (MM) are usually recorded as a multi-level ordinal outcome. One of the goals of drug response studies is to predict which response category any patients belong to with high probability based on their clinical and molecular features. However, as most of genes have small effects, gene-based models may provide limited predictive accuracy. In that case, methods for predicting multi-level ordinal drug responses by incorporating biological pathways are desired but have not been developed yet. Results: We propose a pathway-structured method for predicting multi-level ordinal responses using a two-stage approach. We first develop hierarchical ordinal logistic models and an efficient quasi-Newton algorithm for jointly analyzing numerous correlated variables. Our two-stage approach first obtains the linear predictor (called the pathway score) for each pathway by fitting all predictors within each pathway using the hierarchical ordinal logistic approach, and then combines the pathway scores as new predictors to build a predictive model. We applied the proposed method to two publicly available datasets for predicting multi-level ordinal drug responses in MM using large-scale gene expression data and pathway information. Our results show that our approach not only significantly improved the predictive performance compared with the corresponding gene-based model but also allowed us to identify biologically relevant pathways. Availability and implementation: The proposed approach has been implemented in our R package BhGLM, which is freely available from the public GitHub repository https://github.com/abbyyan3/BhGLM.
Motivation: Molecular analyses suggest that myeloma is composed of distinct sub-types that have different molecular pathologies and various response rates to certain treatments. Drug responses in multiple myeloma (MM) are usually recorded as a multi-level ordinal outcome. One of the goals of drug response studies is to predict which response category any patients belong to with high probability based on their clinical and molecular features. However, as most of genes have small effects, gene-based models may provide limited predictive accuracy. In that case, methods for predicting multi-level ordinal drug responses by incorporating biological pathways are desired but have not been developed yet. Results: We propose a pathway-structured method for predicting multi-level ordinal responses using a two-stage approach. We first develop hierarchical ordinal logistic models and an efficient quasi-Newton algorithm for jointly analyzing numerous correlated variables. Our two-stage approach first obtains the linear predictor (called the pathway score) for each pathway by fitting all predictors within each pathway using the hierarchical ordinal logistic approach, and then combines the pathway scores as new predictors to build a predictive model. We applied the proposed method to two publicly available datasets for predicting multi-level ordinal drug responses in MM using large-scale gene expression data and pathway information. Our results show that our approach not only significantly improved the predictive performance compared with the corresponding gene-based model but also allowed us to identify biologically relevant pathways. Availability and implementation: The proposed approach has been implemented in our R package BhGLM, which is freely available from the public GitHub repository https://github.com/abbyyan3/BhGLM.
Authors: I J F Hofman; M van Duin; E De Bruyne; L Fancello; G Mulligan; E Geerdens; E Garelli; C Mancini; H Lemmens; M Delforge; P Vandenberghe; I Wlodarska; A Aspesi; L Michaux; K Vanderkerken; P Sonneveld; K De Keersmaecker Journal: Leukemia Date: 2016-12-02 Impact factor: 11.528
Authors: E Malek; M A Y Abdel-Malek; S Jagannathan; N Vad; R Karns; A G Jegga; A Broyl; M van Duin; P Sonneveld; F Cottini; K C Anderson; J J Driscoll Journal: Leukemia Date: 2016-09-28 Impact factor: 11.528