Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes

被引：907

作者：

Chen, Rui ^{[1
]}

Mias, George I. ^{[1
]}

Li-Pook-Than, Jennifer ^{[1
]}

Jiang, Lihua ^{[1
]}

Lam, Hugo Y. K. ^{[1
]}

Chen, Rong ^{[2
,3
]}

Miriami, Elana ^{[1
]}

Karczewski, Konrad J. ^{[1
]}

Hariharan, Manoj ^{[1
]}

Dewey, Frederick E. ^{[4
]}

Cheng, Yong ^{[1
]}

Clark, Michael J. ^{[1
]}

Im, Hogune ^{[1
]}

Habegger, Lukas ^{[7
,8
]}

Balasubramanian, Suganthi ^{[7
,8
]}

O'Huallachain, Maeve ^{[1
]}

Dudley, Joel T. ^{[2
,3
]}

Hillenmeyer, Sara ^{[1
]}

Haraksingh, Rajini ^{[1
]}

Sharon, Donald ^{[1
]}

Euskirchen, Ghia ^{[1
]}

Lacroute, Phil ^{[1
]}

Bettinger, Keith ^{[1
]}

Boyle, Alan P. ^{[1
]}

Kasowski, Maya ^{[1
]}

Grubert, Fabian ^{[1
]}

Seki, Scott ^{[2
,3
]}

Garcia, Marco ^{[2
]}

Whirl-Carrillo, Michelle ^{[1
]}

Gallardo, Mercedes ^{[10
,11
]}

Blasco, Maria A. ^{[10
]}

Greenberg, Peter L. ^{[5
]}

Snyder, Phyllis ^{[1
]}

Klein, Teri E. ^{[1
]}

Altman, Russ B. ^{[1
,6
]}

Butte, Atul J. ^{[2
,3
]}

Ashley, Euan A. ^{[4
]}

Gerstein, Mark ^{[7
,8
,9
]}

Nadeau, Kari C. ^{[2
,3
]}

Tang, Hua ^{[1
]}

Snyder, Michael ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Pediat, Div Syst Med, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Pediat, Div Immunol & Allergy, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Div Cardiovasc Med, Ctr Inherited Cardiovasc Dis, Stanford, CA 94305 USA

[5] Stanford Univ, Dept Med, Div Hematol, Stanford, CA 94305 USA

[6] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

[7] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA

[8] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA

[9] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA

[10] Spanish Natl Canc Ctr CNIO, Mol Oncol Program, Telomeres & Telomerase Grp, E-28029 Madrid, Spain

[11] Life Length, E-28003 Madrid, Spain

来源：

CELL | 2012年 / 148卷 / 06期

基金：

欧洲研究理事会;

关键词：

TIME-SERIES ANALYSIS; PERIODICITY DETECTION; GENE ONTOLOGY; RNA; EXPRESSION; IDENTIFICATION; TRANSCRIPT; MUTATIONS; ALGORITHM; DATABASE;

D O I：

10.1016/j.cell.2012.02.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Personalized medicine is expected to benefit from combining genomic information with regular monitoring of physiological states by multiple high-throughput methods. Here, we present an integrative personal omics profile (iPOP), an analysis that combines genomic, transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single individual over a 14 month period. Our iPOP analysis revealed various medical risks, including type 2 diabetes. It also uncovered extensive, dynamic changes in diverse molecular components and biological pathways across healthy and diseased conditions. Extremely high-coverage genomic and transcriptomic data, which provide the basis of our iPOP, revealed extensive heteroallelic changes during healthy and diseased states and an unexpected RNA editing mechanism. This study demonstrates that longitudinal iPOP can be used to interpret healthy and diseased states by connecting genomic information with additional dynamic omics activity.

引用

页码：1293 / 1307

页数：15

共 60 条

[1] CNVnator: An approach to discover, genotype, and characterize typical and atypical CNVs from family and population genome sequencing [J].

Abyzov, Alexej ;

Urban, Alexander E. ;

Snyder, Michael ;

Gerstein, Mark .

GENOME RESEARCH, 2011, 21 (06) :974-984

[2] A method and server for predicting damaging missense mutations [J].

Adzhubei, Ivan A. ;

Schmidt, Steffen ;

Peshkin, Leonid ;

Ramensky, Vasily E. ;

Gerasimova, Anna ;

Bork, Peer ;

Kondrashov, Alexey S. ;

Sunyaev, Shamil R. .

NATURE METHODS, 2010, 7 (04) :248-249

[3] Robust regression for periodicity detection in non-uniformly sampled time-course gene expression data [J].

Ahdesmaki, Miika ;

Lahdesmaki, Harri ;

Gracey, Andrew ;

Shmulevich, Ilya ;

Yli-Harja, Olli .

BMC BIOINFORMATICS, 2007, 8 (1)

[4] A map of human genome variation from population-scale sequencing [J].

Altshuler, David ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Collins, Francis S. ;

De la Vega, Francisco M. ;

Donnelly, Peter ;

Egholm, Michael ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Knoppers, Bartha M. ;

Lander, Eric S. ;

Lehrach, Hans ;

Mardis, Elaine R. ;

McVean, Gil A. ;

Nickerson, DebbieA. ;

Peltonen, Leena ;

Schafer, Alan J. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Deiros, David ;

Metzker, Mike ;

Muzny, Donna ;

Reid, Jeff ;

Wheeler, David ;

Wang, Jun ;

Li, Jingxiang ;

Jian, Min ;

Li, Guoqing ;

Li, Ruiqiang ;

Liang, Huiqing ;

Tian, Geng ;

Wang, Bo ;

Wang, Jian ;

Wang, Wei ;

Yang, Huanming ;

Zhang, Xiuqing ;

Zheng, Huisong ;

Lander, Eric S. ;

Altshuler, David L. ;

Ambrogio, Lauren ;

Bloom, Toby ;

Cibulskis, Kristian ;

Fennell, Tim J. ;

Gabriel, Stacey B. .

NATURE, 2010, 467 (7319) :1061-1073

[5]

[Anonymous], EURASIP J BIOINFORM

[6] Gene Ontology: tool for the unification of biology [J].

Ashburner, M ;

Ball, CA ;

Blake, JA ;

Botstein, D ;

Butler, H ;

Cherry, JM ;

Davis, AP ;

Dolinski, K ;

Dwight, SS ;

Eppig, JT ;

Harris, MA ;

Hill, DP ;

Issel-Tarver, L ;

Kasarskis, A ;

Lewis, S ;

Matese, JC ;

Richardson, JE ;

Ringwald, M ;

Rubin, GM ;

Sherlock, G .

NATURE GENETICS, 2000, 25 (01) :25-29

[7] Clinical assessment incorporating a personal genome [J].

Ashley, Euan A. ;

Butte, Atul J. ;

Wheeler, Matthew T. ;

Chen, Rong ;

Klein, Teri E. ;

Dewey, Frederick E. ;

Dudley, Joel T. ;

Ormond, Kelly E. ;

Pavlovic, Aleksandra ;

Morgan, Alexander A. ;

Pushkarev, Dmitry ;

Neff, Norma F. ;

Hudgins, Louanne ;

Gong, Li ;

Hodges, Laura M. ;

Berlin, Dorit S. ;

Thorn, Caroline F. ;

Sangkuhl, Katrin ;

Hebert, Joan M. ;

Woon, Mark ;

Sagreiya, Hersh ;

Whaley, Ryan ;

Knowles, Joshua W. ;

Chou, Michael F. ;

Thakuria, Joseph V. ;

Rosenbaum, Abraham M. ;

Zaranek, Alexander Wait ;

Church, George M. ;

Greely, Henry T. ;

Quake, Stephen R. ;

Altman, Russ B. .

LANCET, 2010, 375 (9725) :1525-1535

[8] Integrated genomic analyses of ovarian carcinoma [J].

Bell, D. ;

Berchuck, A. ;

Birrer, M. ;

Chien, J. ;

Cramer, D. W. ;

Dao, F. ;

Dhir, R. ;

DiSaia, P. ;

Gabra, H. ;

Glenn, P. ;

Godwin, A. K. ;

Gross, J. ;

Hartmann, L. ;

Huang, M. ;

Huntsman, D. G. ;

Iacocca, M. ;

Imielinski, M. ;

Kalloger, S. ;

Karlan, B. Y. ;

Levine, D. A. ;

Mills, G. B. ;

Morrison, C. ;

Mutch, D. ;

Olvera, N. ;

Orsulic, S. ;

Park, K. ;

Petrelli, N. ;

Rabeno, B. ;

Rader, J. S. ;

Sikic, B. I. ;

Smith-McCune, K. ;

Sood, A. K. ;

Bowtell, D. ;

Penny, R. ;

Testa, J. R. ;

Chang, K. ;

Dinh, H. H. ;

Drummond, J. A. ;

Fowler, G. ;

Gunaratne, P. ;

Hawes, A. C. ;

Kovar, C. L. ;

Lewis, L. R. ;

Morgan, M. B. ;

Newsham, I. F. ;

Santibanez, J. ;

Reid, J. G. ;

Trevino, L. R. ;

Wu, Y. -Q. ;

Wang, M. .

NATURE, 2011, 474 (7353) :609-615

[9] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[10]

Chen K, 2009, NAT METHODS, V6, P677, DOI [10.1038/NMETH.1363, 10.1038/nmeth.1363]

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