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A Sample Selection Strategy to Boost the Statistical Power of Signature Detection in Cancer Expression Profile Studies
Jia, Zhenyu1,2; Wang, Yipeng3; Hu, Yuanjie4; McLaren, Christine5; Yu, Yingyan6,7; Ye, Kai8; Xia, Xiao-Qin9; Koziol, James A.10; Lernhardt, Waldemar11; McClelland, Michael1,12; Mercola, Dan1; Jia, ZY (reprint author), Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA.
2013-02-01
Source PublicationANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
ISSN1871-5206
Volume13Issue:2Pages:203-211
AbstractIn case-control profiling studies, increasing the sample size does not always improve statistical power because the variance may also be increased if samples are highly heterogeneous. For instance, tumor samples used for gene expression assay are often heterogeneous in terms of tissue composition or mechanism of progression, or both; however, such variation is rarely taken into account in expression profiles analysis. We use a prostate cancer prognosis study as an example to demonstrate that solely recruiting more patient samples may not increase power for biomarker detection at all. In response to the heterogeneity due to mixed tissue, we developed a sample selection strategy termed Stepwise Enrichment by which samples are systematically culled based on tumor content and analyzed with t-test to determine an optimal threshold for tissue percentage. The selected tissue-percentage threshold identified the most significant data by balancing the sample size and the sample homogeneity; therefore, the power is substantially increased for identifying the prognostic biomarkers in prostate tumor epithelium cells as well as in prostate stroma cells. This strategy can be generally applied to profiling studies where the level of sample heterogeneity can be measured or estimated.; In case-control profiling studies, increasing the sample size does not always improve statistical power because the variance may also be increased if samples are highly heterogeneous. For instance, tumor samples used for gene expression assay are often heterogeneous in terms of tissue composition or mechanism of progression, or both; however, such variation is rarely taken into account in expression profiles analysis. We use a prostate cancer prognosis study as an example to demonstrate that solely recruiting more patient samples may not increase power for biomarker detection at all. In response to the heterogeneity due to mixed tissue, we developed a sample selection strategy termed Stepwise Enrichment by which samples are systematically culled based on tumor content and analyzed with t-test to determine an optimal threshold for tissue percentage. The selected tissue-percentage threshold identified the most significant data by balancing the sample size and the sample homogeneity; therefore, the power is substantially increased for identifying the prognostic biomarkers in prostate tumor epithelium cells as well as in prostate stroma cells. This strategy can be generally applied to profiling studies where the level of sample heterogeneity can be measured or estimated.
SubtypeArticle
KeywordExpression Profiles Cell-type Heterogeneity Prostate Cancer Statistical Power Sample Size Stepwise Enrichment
Department[Jia, Zhenyu; McClelland, Michael; Mercola, Dan] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA; [Jia, Zhenyu] Guizhou Normal Coll, Guizhou Prov Key Lab Computat Nanomat Sci, Guiyang 550018, Peoples R China; [Wang, Yipeng] AltheaDx Inc, San Diego, CA 92121 USA; [Hu, Yuanjie] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA; [McLaren, Christine] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA; [Yu, Yingyan] Shanghai Jiao Tong Univ, Sch Med, Shanghai Ruijin Hosp, Shanghai 200025, Peoples R China; [Yu, Yingyan] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Digest Surg, Shanghai 200025, Peoples R China; [Ye, Kai] Univ Med Ctr, Mol Epidemiol Sect, Leiden, Netherlands; [Xia, Xiao-Qin] Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China; [Koziol, James A.] Scripps Res Inst, La Jolla, CA 92037 USA; [Lernhardt, Waldemar] Proveri Inc, San Diego, CA 92109 USA; [McClelland, Michael] Vaccine Res Inst San Diego, San Diego, CA 92121 USA
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationNational Institute of Health from NCI Strategic Partners for the Evaluation of Cancer Signatures (SPECS) program [U01 CA114810]; NCI Early Detection Research Network (EDRN) [U01 CA152738]; NCI SBIR [HHSN261200900055C]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine [P30CA62203]; [R01 CA068822] ; National Institute of Health from NCI Strategic Partners for the Evaluation of Cancer Signatures (SPECS) program [U01 CA114810]; NCI Early Detection Research Network (EDRN) [U01 CA152738]; NCI SBIR [HHSN261200900055C]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine [P30CA62203]; [R01 CA068822] ; National Institute of Health from NCI Strategic Partners for the Evaluation of Cancer Signatures (SPECS) program [U01 CA114810]; NCI Early Detection Research Network (EDRN) [U01 CA152738]; NCI SBIR [HHSN261200900055C]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine [P30CA62203]; [R01 CA068822] ; National Institute of Health from NCI Strategic Partners for the Evaluation of Cancer Signatures (SPECS) program [U01 CA114810]; NCI Early Detection Research Network (EDRN) [U01 CA152738]; NCI SBIR [HHSN261200900055C]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine [P30CA62203]; [R01 CA068822]
Indexed BySCI
Language英语
WOS Research AreaOncology ; Pharmacology & Pharmacy
WOS SubjectOncology ; Chemistry, Medicinal
WOS IDWOS:000317848800004
WOS KeywordGENE-EXPRESSION ; BREAST-CANCER ; PROSTATE-CANCER ; MICROARRAY DATA ; DNA MICROARRAY ; DECONVOLUTION ; PATTERNS ; BIOMARKERS ; PROGNOSIS ; SPECIMENS
Funding OrganizationNational Institute of Health from NCI Strategic Partners for the Evaluation of Cancer Signatures (SPECS) program [U01 CA114810]; NCI Early Detection Research Network (EDRN) [U01 CA152738]; NCI SBIR [HHSN261200900055C]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine [P30CA62203]; [R01 CA068822] ; National Institute of Health from NCI Strategic Partners for the Evaluation of Cancer Signatures (SPECS) program [U01 CA114810]; NCI Early Detection Research Network (EDRN) [U01 CA152738]; NCI SBIR [HHSN261200900055C]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine [P30CA62203]; [R01 CA068822] ; National Institute of Health from NCI Strategic Partners for the Evaluation of Cancer Signatures (SPECS) program [U01 CA114810]; NCI Early Detection Research Network (EDRN) [U01 CA152738]; NCI SBIR [HHSN261200900055C]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine [P30CA62203]; [R01 CA068822] ; National Institute of Health from NCI Strategic Partners for the Evaluation of Cancer Signatures (SPECS) program [U01 CA114810]; NCI Early Detection Research Network (EDRN) [U01 CA152738]; NCI SBIR [HHSN261200900055C]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine [P30CA62203]; [R01 CA068822]
Citation statistics
Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/19344
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorJia, ZY (reprint author), Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA.
Affiliation1.Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA
2.Guizhou Normal Coll, Guizhou Prov Key Lab Computat Nanomat Sci, Guiyang 550018, Peoples R China
3.AltheaDx Inc, San Diego, CA 92121 USA
4.Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA
5.Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA
6.Shanghai Jiao Tong Univ, Sch Med, Shanghai Ruijin Hosp, Shanghai 200025, Peoples R China
7.Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Digest Surg, Shanghai 200025, Peoples R China
8.Univ Med Ctr, Mol Epidemiol Sect, Leiden, Netherlands
9.Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China
10.Scripps Res Inst, La Jolla, CA 92037 USA
11.Proveri Inc, San Diego, CA 92109 USA
12.Vaccine Res Inst San Diego, San Diego, CA 92121 USA
Recommended Citation
GB/T 7714
Jia, Zhenyu,Wang, Yipeng,Hu, Yuanjie,et al. A Sample Selection Strategy to Boost the Statistical Power of Signature Detection in Cancer Expression Profile Studies[J]. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY,2013,13(2):203-211.
APA Jia, Zhenyu.,Wang, Yipeng.,Hu, Yuanjie.,McLaren, Christine.,Yu, Yingyan.,...&Jia, ZY .(2013).A Sample Selection Strategy to Boost the Statistical Power of Signature Detection in Cancer Expression Profile Studies.ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY,13(2),203-211.
MLA Jia, Zhenyu,et al."A Sample Selection Strategy to Boost the Statistical Power of Signature Detection in Cancer Expression Profile Studies".ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY 13.2(2013):203-211.
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