title: Impact of bioinformatic procedures in the development and translation of high-throughput molecular classifiers in oncology.
abstract: The progressive introduction of high-throughput molecular techniques in the clinic allows for the extensive and systematic exploration of multiple biologic layers of tumors. Molecular profiles and classifiers generated from these assays represent the foundation of what the National Academy describes as the future of "precision medicine". However, the analysis of such complex data requires the implementation of sophisticated bioinformatic and statistical procedures. It is critical that oncology practitioners be aware of the advantages and limitations of the methods used to generate classifiers to usher them into the clinic. This article uses publicly available expression data from patients with non-small cell lung cancer to first illustrate the challenges of experimental design and preprocessing of data before clinical application and highlights the challenges of high-dimensional statistical analysis. It provides a roadmap for the translation of such classifiers to clinical practice and makes key recommendations for good practice.
authors.affiliation: Sage Bionetworks, Seattle, WA 98109, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Ferté
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Trister
authors.forename: Erich
authors.initials: E
authors.lastname: Huang
authors.forename: Brian M
authors.initials: BM
authors.lastname: Bot
authors.forename: Justin
authors.initials: J
authors.lastname: Guinney
authors.forename: Frederic
authors.initials: F
authors.lastname: Commo
authors.forename: Solveig
authors.initials: S
authors.lastname: Sieberts
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Friend
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011786:Quality Control; D012107:Research Design; D057170:Translational Research, Biomedical