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KMW: conceived the methods, provided biological interpretation.
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Clearly such high false positive rates have serious implications for the conclusions drawn by any study which uses independence assumption methods to provide biological interpretation of microarray data.
YYL provided biological analysis.
ALR: provided biological interpretation.
FZ provided biological samples.
JW Huh provided biological direction.
Gene set testing, in which enrichment of significant differentially expressed genes is sought among gene sets, is by now a standard method to provide biological interpretation for gene expression data.
Moreover, these methods provide a biological metric to filter the vast amount of publicly available microarray experiments for subsequent meta-analysis and systems biology research.
Since protein selection methods provide simultaneous biological and structural data on the compound(s) to be analyzed, the detection of false positives due to library impurities or degradation of compounds in a bioactive mixture is very improbable.
Furthermore, we cannot conclude that the unique categories found by any method provided additional biological insight supporting the differences observed without extensive individual validation with a variety of techniques, which is beyond the scope of this work.
We believe that our scoring matrixes and template-based method are able to provide biological insights and binding mechanisms of TCR-pMHC and to reveal the immune reactions for peptide vaccine designs.
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