Sorting points into neighborhoods (SPIN): data analysis and visualization by ordering distance matrices.
CONCLUSIONS
We introduce a novel unsupervised approach for the organization and visualization of multidimensional data. At the heart of the method is a presentation of the full pairwise distance matrix of the data points, viewed in pseudocolor. The ordering of points is iteratively permuted in search of a linear ordering, which can be used to study embedded shapes. Several examples indicate how the shapes of certain structures in the data (elongated, circular and compact) manifest themselves visually in our permuted distance matrix. It is important to identify the elongated objects since they are often associated with a set of hidden variables, underlying continuous variation in the data. The problem of determining an optimal linear ordering is shown to be NP-Complete, and therefore an iterative search algorithm with O(n3) step-complexity is suggested. By using sorting points into neighborhoods, i.e. SPIN to analyze colon cancer expression data we were able to address the serious problem of sample heterogeneity, which hinders identification of metastasis related genes in our data. Our methodology brings to light the continuous variation of heterogeneity--starting with homogeneous tumor samples and gradually increasing the amount of another tissue. Ordering the samples according to their degree of contamination by unrelated tissue allows the separation of genes associated with irrelevant contamination from those related to cancer progression.


BACKGROUND
Software package will be available for academic users upon request.
Tsafrir
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Department of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel. fedafna@wisemail.weizmann.ac.il
Tsafrir
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Ein-Dor
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Zuk
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Notterman
D A
DA
Domany
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D000465:Algorithms; D014408:Biomarkers, Tumor / Q000145:classification / Q000378:metabolism*; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D003196:Computer Graphics; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D003936:Diagnosis, Computer-Assisted / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D016247:Information Storage and Retrieval / Q000379:methods*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000145:classification / Q000378:metabolism*; D010363:Pattern Recognition, Automated / Q000379:methods; D012984:Software; D014584:User-Computer Interface
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins