Alizadeh et. al. (2000)ClusteringHierarchical ClusteringDivisiveAgglomerativeAverage-Linkage MethodDiffuse Large B-cell LymphomaLymphochipExpression AnalysisFigure 1Figure 2:Figure 3:Figure 4:Figure 5ConclusionsAlizadeh et. al. (2000)Stephen Ayers12/2/01Clustering“Clustering is finding a natural grouping in a set of data, so that samples within a cluster will be more similar to each other than they are to samples in other clusters.”Finding groups of correlated genes “signature groups”Genes without well established relationshipsExtract features of groupsHierarchical Clustering•Tiers of points from a bottom layer of 1 point in each of n clusters to top level of n points, all in one cluster•Usually represented in dendrogramDivisive•Top-down•Start with all samples and successively split into separate clustersAgglomerative•Bottom-up approach •Less computationally intensive•Start with n singletons and successively merge clusters–Place all values in separate clusters–Merge most similar clusters into higher clusters–Repeat until all clusters have been mergedAverage-Linkage Method•Available <<http://rana.stanford.edu/clustering >>1. Compute similarity matrix2. Scan matrix to find most highest similarity•Uses form of the correlation coefficient3. A node is created between these values4. Values are replaced by nodeDiffuse Large B-cell Lymphoma•Most common subtype of non-Hodgkin’s Lymphoma•25,000 cases/year•40% of patients respond well•Possible undetected heterogeneity •Found 2 classes using clustering (Eisen 1998): Germinal Center B-like and Activated B-likeLymphochip•17,856 cDNA clones total•12,069 germinal center B-cell library •2,338 lymphomic cancer genes•3,186 genes important to lymphocyte or cancer biology•¼ of genes = duplicatesExpression Analysis•DLBCL, Follicular Lymphoma, Chronic Lympohcytic Leukemia•Lymphocyte subpopulations with a range of conditions•-normal human tonsils, lymph nodes•-lymphoma, leukemia cell linesFigure 1Figure 2:Figure 3:Figure 4:GCActivatedFigure 5Conclusions•More categories likely•Changes in treatment•Possible drug
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