Methods for simultaneously identifying coherent local clusters with smooth global patterns in gene expression profiles.
BACKGROUND
The hierarchical clustering tree (HCT) with a dendrogram 1 and the singular value decomposition (SVD) with a dimension-reduced representative map 2 are popular methods for two-way sorting the gene-by-array matrix map employed in gene expression profiling. While HCT dendrograms tend to optimize local coherent clustering patterns, SVD leading eigenvectors usually identify better global grouping and transitional structures.


RESULTS
This study proposes a flipping mechanism for a conventional agglomerative HCT using a rank-two ellipse (R2E, an improved SVD algorithm for sorting purpose) seriation by Chen 3 as an external reference. While HCTs always produce permutations with good local behaviour, the rank-two ellipse seriation gives the best global grouping patterns and smooth transitional trends. The resulting algorithm automatically integrates the desirable properties of each method so that users have access to a clustering and visualization environment for gene expression profiles that preserves coherent local clusters and identifies global grouping trends.


CONCLUSIONS
We demonstrate, through four examples, that the proposed method not only possesses better numerical and statistical properties, it also provides more meaningful biomedical insights than other sorting algorithms. We suggest that sorted proximity matrices for genes and arrays, in addition to the gene-by-array expression matrix, can greatly aid in the search for comprehensive understanding of gene expression structures. Software for the proposed methods can be obtained at http://gap.stat.sinica.edu.tw/Software/GAP.
Tien
Yin-Jing
YJ
Institute of Statistical Science, Academia Sinica, Taipei, 11529, Taiwan. gary@stat.sinica.edu.tw
Lee
Yun-Shien
YS
Wu
Han-Ming
HM
Chen
Chun-Houh
CH
D000465:Algorithms; D016000:Cluster Analysis; D003196:Computer Graphics; D020869:Gene Expression Profiling / Q000379:methods*; D005810:Multigene Family / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010363:Pattern Recognition, Automated / Q000379:methods*; D020543:Proteome / Q000378:metabolism*; D012984:Software; D014584:User-Computer Interface
D020543:Proteome