title: Gene integrated set profile analysis: a context-based approach for inferring biological endpoints.
abstract: The identification of genes with specific patterns of change (e.g. down-regulated and methylated) as phenotype drivers or samples with similar profiles for a given gene set as drivers of clinical outcome, requires the integration of several genomic data types for which an 'integrate by intersection' (IBI) approach is often applied. In this approach, results from separate analyses of each data type are intersected, which has the limitation of a smaller intersection with more data types. We introduce a new method, GISPA (Gene Integrated Set Profile Analysis) for integrated genomic analysis and its variation, SISPA (Sample Integrated Set Profile Analysis) for defining respective genes and samples with the context of similar, a priori specified molecular profiles. With GISPA, the user defines a molecular profile that is compared among several classes and obtains ranked gene sets that satisfy the profile as drivers of each class. With SISPA, the user defines a gene set that satisfies a profile and obtains sample groups of profile activity. Our results from applying GISPA to human multiple myeloma (MM) cell lines contained genes of known profiles and importance, along with several novel targets, and their further SISPA application to MM coMMpass trial data showed clinical relevance.
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA 30333, USA Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30333, USA Jeanne.kowalski@emory.edu.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Kowalski
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30333, USA.
authors.forename: Bhakti
authors.initials: B
authors.lastname: Dwivedi
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30333, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Newman
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA 30333, USA Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30333, USA.
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Switchenko
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA 30333, USA.
authors.forename: Rini
authors.initials: R
authors.lastname: Pauly
authors.affiliation: Department of Biomedical Informatics and Neurology, School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Gutman
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA 30333, USA.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Arora
authors.affiliation: Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Khanjan
authors.initials: K
authors.lastname: Gandhi
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30333, USA.
authors.forename: Kylie
authors.initials: K
authors.lastname: Ainslie
authors.affiliation: Centers for Disease Control, Atlanta, GA 30322, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Doho
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30333, USA Department of Biomedical Informatics and Neurology, School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA 30333, USA Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Moreno
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA 30333, USA Department of Radiation Oncology, School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rossi
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA 30333, USA Department of Radiation Oncology, School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Vertino
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA 30333, USA Department of Hematology and Medical Oncology, School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA 30333, USA Department of Hematology and Medical Oncology, School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Leon
authors.initials: L
authors.lastname: Bernal-Mizrachi
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA 30333, USA Department of Hematology and Medical Oncology, School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Boise
mesh_terms: D045744:Cell Line, Tumor; D019175:DNA Methylation; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D023281:Genomics / Q000379:methods*; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics / Q000401:mortality; D009154:Mutation; D011379:Prognosis
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