Statistical theory and the evaluation of Cox's proportional hazards model regularized by various penalties for survival DNA microarray expression data

• Project/Area Number: 24650149
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Statistical science
• Research Institution: Niigata University
• Principal Investigator: AKAZAWA Kohei 新潟大学, 医歯学総合病院, 教授 (10175771)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 比例ハザードモデル / 罰則化 / DNAマイクロアレイデータ / 生存時間解析 / バイオインフォマティックス / マイクロアレイデータ / モンテカルロシミュレーション / 検出力 / Elastic net罰則化 / 疾患感受性遺伝子

Research Abstract

In this study, we created programs using the R language to calculate statistical properties of Cox's proportional hazards model regularized by various penalties, including the statistical power based on the prognostic index, and conducted simulation experiments under various conditions of DNA microarray expression data with survival time. The results showed that when the number of candidate genes is larger than the sample size, the power of a validation set for penalized methods is greater than for stepwise methods in many cases. This tendency is most remarkable for the penalized methods including both the L1-norm and the L2-norm. Furthermore, we verified our programs to actual microarray gene expression data with survival time data to confirm their validity. Our simulation programs for Cox's proportional hazards model regularized by various penalties are very useful for planning DNA microarray studies or for evaluating the results of such studies.

Research Products

• [Journal Article] SORL1 is genetically associated with neuropathologically characterized late-onset Alzheimer's disease (2013)
  • Author(s): Wen Y, Miyashita A, Kitamura N, Tsukie T, Saito Y, Hatsuta H, Murayama S, Kakita A, Takahashi H, Akatsu H, Yamamoto T, Kosaka K, Yamaguchi H, Akazawa K, Ihara Y, Kuwano R
  • Journal Title: J Alzheimers Dis. Volume: 35(2) Pages: 387-394
  • Peer Reviewed
• [Journal Article] SORL1 is genetically associated with neuropathologically characterized late-onset Alzheimer's disease (2013)
  • Author(s): Wen Y, Miyashita A, Kitamura N, Tsukie T, Saito Y, Hatsuta H, Murayama S, et al.
  • Journal Title: J Alzheimers Dis Volume: 35(2) Issue: 2 Pages: 387-94
  • DOI: 10.3233/jad-122395
  • Peer Reviewed
• [Journal Article] High-Risk Ovarian Cancer Based on 126-Gene Expression Signature Is Uniquely Characterized by Downregulation of Antigen Presentation Pathway (2012)
  • Author(s): Yoshihara K, Tsunoda T, Shigemizu D, Fujiwara H, Hatae M, Fujiwara H, Masuzaki H, Katabuchi H, KawakamiY, Okamoto A, Nogawa T, Matsumura N, Udagawa Y, Saito T, Itamochi H, Takano M, Miyagi E, Sudo T, Ushijima K, Iwase H, Seki H, Terao Y, Enomoto T, Mikami M, Akazawa K, Tsuda H, Moriya T, Tajima A, Inoue I, and Kenichi Tanaka for The Japanese Serous Ovarian Cancer Study Group
  • Journal Title: Clin Cancer Res 2012 Volume: 18 Pages: 1374-1385
  • Peer Reviewed
• [Journal Article] High-Risk Ovarian Cancer Based on 126-Gene Expression Signature Is Uniquely Characterized by Downregulation of Antigen Presentation Pathway (2012)
  • Author(s): Kosuke Yoshihara
  • Journal Title: Clinical Cancer Research Volume: 18 Issue: 5 Pages: 1374-1385
  • DOI: 10.1158/1078-0432.ccr-11-2725
  • Peer Reviewed
• [Presentation] 疾患感受性遺伝子同定のためのマイクロアレイデータ解析法に関する研究―elastic net罰則化項により最適化されたCoxの比例ハザードモデルの特性について (2012)
  • Author(s): 北村信隆, 赤澤宏平
  • Organizer: 第32回日本医療情報学連合大会
  • Place of Presentation: 新潟・朱鷺メッセ
• [Presentation] 疾患感受性遺伝子同定のためのマイクロアレイデータ解析法に関する研究－elastic net罰則化項により最適化されたCox比例ハザードモデルの特性について－ (2012)
  • Author(s): 北村 信隆
  • Organizer: 第32回 医療情報学連合大会
  • Place of Presentation: 朱鷺メッセ新潟コンベンションセンター