Annette M Molinaro1, Karen Lostritto, Mark van der Laan. 1. Division of Biostatistics, Yale University Schools of Public Health and Medicine, 60 College St., New Haven, CT 06519, USA. annette.molinaro@yale.edu
Abstract
MOTIVATION: Until now, much of the focus in cancer has been on biomarker discovery and generating lists of univariately significant genes, as well as epidemiological and clinical measures. These approaches, although significant on their own, are not effective for elucidating the synergistic qualities of the numerous components in complex diseases. These components do not act one at a time, but rather in concert with numerous others. A compelling need exists to develop analytically sound and computationally advanced methods that elucidate a more biologically meaningful understanding of the mechanisms of cancer initiation and progression by taking these interactions into account. RESULTS: We propose a novel algorithm, partDSA, for prediction when several variables jointly affect the outcome. In such settings, piecewise constant estimation provides an intuitive approach by elucidating interactions and correlation patterns in addition to main effects. As well as generating 'and' statements similar to previously described methods, partDSA explores and chooses the best among all possible 'or' statements. The immediate benefit of partDSA is the ability to build a parsimonious model with 'and' and 'or' conjunctions that account for the observed biological phenomena. Importantly, partDSA is capable of handling categorical and continuous explanatory variables and outcomes. We evaluate the effectiveness of partDSA in comparison to several adaptive algorithms in simulations; additionally, we perform several data analyses with publicly available data and introduce the implementation of partDSA as an R package. AVAILABILITY: http://cran.r-project.org/web/packages/partDSA/index.html CONTACT: annette.molinaro@yale.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: Until now, much of the focus in cancer has been on biomarker discovery and generating lists of univariately significant genes, as well as epidemiological and clinical measures. These approaches, although significant on their own, are not effective for elucidating the synergistic qualities of the numerous components in complex diseases. These components do not act one at a time, but rather in concert with numerous others. A compelling need exists to develop analytically sound and computationally advanced methods that elucidate a more biologically meaningful understanding of the mechanisms of cancer initiation and progression by taking these interactions into account. RESULTS: We propose a novel algorithm, partDSA, for prediction when several variables jointly affect the outcome. In such settings, piecewise constant estimation provides an intuitive approach by elucidating interactions and correlation patterns in addition to main effects. As well as generating 'and' statements similar to previously described methods, partDSA explores and chooses the best among all possible 'or' statements. The immediate benefit of partDSA is the ability to build a parsimonious model with 'and' and 'or' conjunctions that account for the observed biological phenomena. Importantly, partDSA is capable of handling categorical and continuous explanatory variables and outcomes. We evaluate the effectiveness of partDSA in comparison to several adaptive algorithms in simulations; additionally, we perform several data analyses with publicly available data and introduce the implementation of partDSA as an R package. AVAILABILITY: http://cran.r-project.org/web/packages/partDSA/index.html CONTACT: annette.molinaro@yale.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Authors: Andreas Rosenwald; George Wright; Wing C Chan; Joseph M Connors; Elias Campo; Richard I Fisher; Randy D Gascoyne; H Konrad Muller-Hermelink; Erlend B Smeland; Jena M Giltnane; Elaine M Hurt; Hong Zhao; Lauren Averett; Liming Yang; Wyndham H Wilson; Elaine S Jaffe; Richard Simon; Richard D Klausner; John Powell; Patricia L Duffey; Dan L Longo; Timothy C Greiner; Dennis D Weisenburger; Warren G Sanger; Bhavana J Dave; James C Lynch; Julie Vose; James O Armitage; Emilio Montserrat; Armando López-Guillermo; Thomas M Grogan; Thomas P Miller; Michel LeBlanc; German Ott; Stein Kvaloy; Jan Delabie; Harald Holte; Peter Krajci; Trond Stokke; Louis M Staudt Journal: N Engl J Med Date: 2002-06-20 Impact factor: 91.245
Authors: Seunggu J Han; W Caleb Rutledge; Annette M Molinaro; Susan M Chang; Jennifer L Clarke; Michael D Prados; Jennie W Taylor; Mitchel S Berger; Nicholas A Butowski Journal: Neurosurgery Date: 2015-08 Impact factor: 4.654
Authors: Seunggu J Han; Dario J Englot; Harjus Birk; Annette M Molinaro; Susan M Chang; Jennifer L Clarke; Michael D Prados; Jennie W Taylor; Mitchel S Berger; Nicholas A Butowski Journal: Neurosurgery Date: 2015-08 Impact factor: 4.654
Authors: Annette M Molinaro; John K Wiencke; Gayathri Warrier; Devin C Koestler; Pranathi Chunduru; Ji Yoon Lee; Helen M Hansen; Sean Lee; Joaquin Anguiano; Terri Rice; Paige M Bracci; Lucie McCoy; Lucas A Salas; Brock C Christensen; Margaret Wrensch; Karl T Kelsey; Jennie W Taylor; Jennifer L Clarke Journal: J Natl Cancer Inst Date: 2022-03-08 Impact factor: 11.816
Authors: Annette M Molinaro; Jennette D Sison; Britt-Marie Ljung; Thea D Tlsty; Karla Kerlikowske Journal: Breast Cancer Res Treat Date: 2016-05-04 Impact factor: 4.872
Authors: John K Wiencke; Ze Zhang; Devin C Koestler; Lucas A Salas; Annette M Molinaro; Brock C Christensen; Karl T Kelsey Journal: Epigenetics Date: 2021-03-30 Impact factor: 4.528
Authors: Annette M Molinaro; Shawn Hervey-Jumper; Ramin A Morshed; Jacob Young; Seunggu J Han; Pranathi Chunduru; Yalan Zhang; Joanna J Phillips; Anny Shai; Marisa Lafontaine; Jason Crane; Ankush Chandra; Patrick Flanigan; Arman Jahangiri; Gino Cioffi; Quinn Ostrom; John E Anderson; Chaitra Badve; Jill Barnholtz-Sloan; Andrew E Sloan; Bradley J Erickson; Paul A Decker; Matthew L Kosel; Daniel LaChance; Jeanette Eckel-Passow; Robert Jenkins; Javier Villanueva-Meyer; Terri Rice; Margaret Wrensch; John K Wiencke; Nancy Ann Oberheim Bush; Jennie Taylor; Nicholas Butowski; Michael Prados; Jennifer Clarke; Susan Chang; Edward Chang; Manish Aghi; Philip Theodosopoulos; Michael McDermott; Mitchel S Berger Journal: JAMA Oncol Date: 2020-04-01 Impact factor: 33.006