title: Integrated modeling of clinical and gene expression information for personalized prediction of disease outcomes.
abstract: We describe a comprehensive modeling approach to combining genomic and clinical data for personalized prediction in disease outcome studies. This integrated clinicogenomic modeling framework is based on statistical classification tree models that evaluate the contributions of multiple forms of data, both clinical and genomic, to define interactions of multiple risk factors that associate with the clinical outcome and derive predictions customized to the individual patient level. Gene expression data from DNA microarrays is represented by multiple, summary measures that we term metagenes; each metagene characterizes the dominant common expression pattern within a cluster of genes. A case study of primary breast cancer recurrence demonstrates that models using multiple metagenes combined with traditional clinical risk factors improve prediction accuracy at the individual patient level, delivering predictions more accurate than those made by using a single genomic predictor or clinical data alone. The analysis also highlights issues of communicating uncertainty in prediction and identifies combinations of clinical and genomic risk factors playing predictive roles. Implicated metagenes identify gene subsets with the potential to aid biological interpretation. This framework will extend to incorporate any form of data, including emerging forms of genomic data, and provides a platform for development of models for personalized prognosis.
authors.affiliation: Institute of Statistics and Decision Sciences, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pittman
authors.forename: Erich
authors.initials: E
authors.lastname: Huang
authors.forename: Holly
authors.initials: H
authors.lastname: Dressman
authors.forename: Cheng-Fang
authors.initials: CF
authors.lastname: Horng
authors.forename: Skye H
authors.initials: SH
authors.lastname: Cheng
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Tsou
authors.forename: Chii-Ming
authors.initials: CM
authors.lastname: Chen
authors.forename: Andrea
authors.initials: A
authors.lastname: Bild
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Iversen
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Huang
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Nevins
authors.forename: Mike
authors.initials: M
authors.lastname: West
mesh_terms: D001499:Bayes Theorem; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013624:Taiwan