Data analysis in microarray experiment
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1 Chinese Bulletin of Life Sciences Vol. 16, No. 1 Feb., (004) Q33 A Data analysis in microarray experiment YANG Chang, FANG Fu-De * (National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS and PUMC, Beijing , China) Abstract: Genechip, representing the integration of multiple scientific field progress, is a newly developing high technology used to solve biology puzzle with automated and high-flux features. It has a successful application in large-scale research in genes function. After a relative long developing period, the method how to efficiently analyse mass data generated by chip experiment has become a hotspot in the chip research community. In principal, the method can be divided into two categories, the unsupervised method and the supervised method. Besides data analysis itself, two procedures performing before and after the analysis need to be paid attention to: the former is data normalization and reduction, the later is statistical test and biologic verification. Many commonly used statistical approaches and their merits and demerits will be introduced. Key words: genechip; data analysis 1 genechip [1] biochip ( chip) microarray Affymetrix (1977 ) (1941 ) *
2 4 ONA c CDA [] (matrix) 3 (Format I) (Format II) (normalization ) [] 3.1 [] 3. [3] mrna Cy5 Cy3 3.3 [3] mrna Cy5 Cy3 Cy5 Cy3 ratio log ratio Cy5/Cy3 (vector) LOWESS (locally weighted scatterplot smoothing) 3.4 [3] A A
3 43 K T K =R K /G K R K G K [7] D's(n-1) [8] 4 (filtering) [5] (dimension reduction) [4] (unsupervised) (supervised) (non-redundant) 5.1 (unsupervised grouping) [4] (cluster analysis) 7 (1) () (classification) (hierarchical clustering) Bayesian K (K-means clustering) (self-organizing maps, SOMs) (principal component analysis, PCA) (two-way clustering) [9] (deterministic annealing) [9] (graph-theoretic) [10] (neural network clustering) (multidimensional scaling analysis) [11] (divisive) (agglomerative) K 5 (legal genes) (active genes) [6] (relevant gene informative gene) [6]
4 44 (metric distances) (semi-metric distances) (Euclidean distance) d ij i j (1)d ij 0 () d ij =d ji (3)d ii =0 (average-linkage) UPGM (unweighted pair-group method average) (4) i j k d ik d ij +d jk (x 1,x,x 3 ) (y 1,y,y 3 ) d 1 x i y i X Y i n K-means (self-organized maps, SOMs) [3] 5.1. K-means K-means (similarity matrix) k (hierarchical clustering) [3,1] (vector) (cluster) k ( 1) (single-linkage) 1 K-means (complete-linkage) (self-organized maps SOMs) [3] SOMs 3
5 principal component analysis PCA [3] PCA PCA PCA 1 SOMs) 5. (supervised grouping) [4] ( K-means Time 87.5% 8 A C E B D (classification) (support vector machine SVM) [13] SOMs SVM SOMs K-means SVM SOMs
6 46 q P q q Bonferroni Bon- P (overabundance P ferroni analysis) P P [6] htm) 7 ( PRM [15] [6] probabilistic relational models, logistic (neural network) analysis LDA) (1inear discriminant [16] GenMAPP 6 genmapp.org Pubgene t Stanford (significance 8 analysis of microarrays, SAM) Excel ~tibs/sam Ben-Dor [14] (the threshold number of misclassification, TNoM) (score)
7 47 Windows Macintosh Solaris Unix 1 Cluster Michael B. Eisen Hierarchical Clustering PCA SOMs K-means Clustering Planet [19].10 TreeView stanford.edu/microarray/smd Genesis [17] AMADA [18] (data mining) BRCA (systematic analysis) [19] [1] Cheung V G, Morley M, Aguilar F, et al. Making and reading microarrays. Nat Genet, 1999, 1: 15~19 []. [M]. :, 000 [3] Quackenbush J. Computational genetics: computational analysis of microarray data. Nat Rev Genet, 001, : 418~47
8 48 [4] Raychaudhuri S, Sutphin P D, Chang J T, et al. Basic microarray analysis: grouping and feature reduction. Trends Biotechnol, 001, 19(5): 189~193 [5] Fellenberg K, Hauser N C, Brors B, et al. Correspondence analysis applied to microarray data. Proc Natl Acad Sci USA, 001, 98(19): 10781~10786 [6] Kaminski N, Friedman N. Practical approaches to analyzing results of microarray experiments. Am J Respir Cell Mol Biol, 00, 7(): 15~13 [7] Schena M, Shalon D, Heller R, et al. Parallel human genome analysis: microarray-based expression monitoring of 1000 genes. Proc Natl Acad Sci U S A, 1996, 93(0): 10614~10619 [8] Lee J H, Kaminski N, Dolganov G, et al. Interleukin-13 induces dramatically different transcriptional programs in three human airway cell types. Am J Respir Cell Mol Biol, 001, 5: 474~485 [9] Alon U, Barkai N, Notterman D A, et al. Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays. Proc Natl Acad Sci USA, 1999, 96: 6745~6750 [10] Ben-Dor A, Shamir R, Yakhini Z. Clustering gene expression patterns. J Comput Biol, 1999, 6: 81~97 [11] Bittner M, Meltzer P, Trent J. Data analysis and integration: of steps and arrows. Nature Genet, 1999, : 13~15 [1] Eisen M B, Spellman P T, Brown P O, et al. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA, 1998, 95: 14863~14868 [13] Tamayo P, Slonim D, Mesirov J, et al. Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoietic differentiation. Proc Natl Acad Sci USA, 1999, 96: 907~91 [14] Ben-Dor A, Bruhn L, Friedman N, et al. Tissue classification with gene expression profiles. J Comput Biol, 000, 7: 559~583 [15] Segal E, Taskar B, Gasch A, et al. Rich probabilistic models for gene expression. Bioinformatics, 001, 17: S43~S5 [16] Dahlquist K D, Salomonis N, Vranizan K, et al. GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways. Nature Genet, 00, 31: 19~0 [17] Sturn A, Quackenbush J, Trajanoski Z. Genesis: cluster analysis of microarray data. Bioinformatics, 00, 18(1): 07~08 [18] Xia X H, Xie Z. AMADA: analysis of microarray data. Bioinformatics, 001, 17: 569~570 [19] Planet P J, DeSalle R, Siddall M, et al. Systematic analysis of microarray data: ordering and interpreting patterns of gene expression. Genome Res, 001, 11(7): 1149~1155
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