Taking a Systems Approach to the Identification of Novel Therapeutic Targets and Biomarkers

被引:0
作者
Dunn, David A. [2 ]
Apanovitch, Donald [1 ]
Follettie, Max
He, Tao
Ryan, Terence
机构
[1] Pfizer Inc, Pearl River, NY 10965 USA
[2] Pfizer Inc, Collegeville, PA 19426 USA
关键词
Chemical biology; high content screening; multivariate analysis; ontological classification; predictive modeling; proteomics; transcriptomics; MASS-SPECTROMETRY; SMALL MOLECULES; DRUG DISCOVERY; IN-VIVO; CHEMICAL GENETICS; BIOLOGY; CANCER; PATHWAY; MICROARRAYS; PROTEOMICS;
D O I
暂无
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
Systems biology focuses on the roles of cellular pathways and networks rather than single biomolecules to describe biological function. A systems view of biology requires technology that can generate and quantitatively analyze, large multi-dimensional data sets from many different sources. New technology has made this approach to drug discovery increasingly feasible. Detailed changes in cellular phenotype can be quantitatively measured using high content phenotypic screens. Changes in a cells entire transcriptome or proteome can be profiled in detail. Libraries of small molecules, peptides or poly-nucleotides such as siRNA can be screened to identify perturbagens that modulate transcriptomic, proteomic and cellular phenotypic signatures. These molecular agents can be used to deconvolute pathways and networks. The power of these technologies lies in their ability to generate complex biological data at massive scales. Integration and analysis of this multi-parametric data is vital to systems biology research. Patterns and relationships within these data sets can be revealed using factor and principal component analysis. These patterns can point to pathways that are relevant to specific biological processes making the ultimate goal of understanding the biology of a cell at the systems level possible.
引用
收藏
页码:721 / 734
页数:14
相关论文
共 139 条
[1]   High content screening applied to large-scale cell biology [J].
Abraham, VC ;
Taylor, DL ;
Haskins, JR .
TRENDS IN BIOTECHNOLOGY, 2004, 22 (01) :15-22
[2]   Biomaterial microarrays: rapid, microscale screening of polymer-cell interaction [J].
Anderson, DG ;
Putnam, D ;
Lavik, EB ;
Mahmood, TA ;
Langer, R .
BIOMATERIALS, 2005, 26 (23) :4892-4897
[3]   Integrating cytomics and proteomics [J].
Bernas, T ;
Grégori, G ;
Asem, EK ;
Robinson, JP .
MOLECULAR & CELLULAR PROTEOMICS, 2006, 5 (01) :2-13
[4]   Pharmacogenomic approaches in clinical studies to identify biomarkers of safety and efficacy [J].
Burczynski, M. E. .
TOXICOLOGY LETTERS, 2009, 186 (01) :18-21
[5]   Can cell systems biology rescue drug discovery? [J].
Butcher, EC .
NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (06) :461-467
[6]   Systems biology in drug discovery [J].
Butcher, EC ;
Berg, EL ;
Kunkel, EJ .
NATURE BIOTECHNOLOGY, 2004, 22 (10) :1253-1259
[7]  
C, 2003, DRUG DISCOV TODAY, V8, P168
[8]   Evaluation of DNA microarray results with quantitative gene expression platforms [J].
Canales, Roger D. ;
Luo, Yuling ;
Willey, James C. ;
Austermiller, Bradley ;
Barbacioru, Catalin C. ;
Boysen, Cecilie ;
Hunkapiller, Kathryn ;
Jensen, Roderick V. ;
Knight, Charles R. ;
Lee, Kathleen Y. ;
Ma, Yunqing ;
Maqsodi, Botoul ;
Papallo, Adam ;
Peters, Elizabeth Herness ;
Poulter, Karen ;
Ruppel, Patricia L. ;
Samaha, Raymond R. ;
Shi, Leming ;
Yang, Wen ;
Zhang, Lu ;
Goodsaid, Federico M. .
NATURE BIOTECHNOLOGY, 2006, 24 (09) :1115-1122
[9]   Transdominant genetic analysis of a growth control pathway [J].
Caponigro, G ;
Abedi, MR ;
Hurlburt, AP ;
Maxfield, A ;
Judd, W ;
Kamb, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (13) :7508-7513
[10]   Image-based chemical screening [J].
Carpenter, Anne E. .
NATURE CHEMICAL BIOLOGY, 2007, 3 (08) :461-465