SELF-DIRECTED METHOD FOR CELL-TYPE IDENTIFICATION AND SEPARATION OF GENE EXPRESSION MICROARRAYS

摘要

Gene expression analysis is generally performed on heterogeneous tissue samples consisting of multiple cell types. Current methods developed to separate heterogeneous gene expression rely on prior knowledge of the cell-type composition and/or signatures—these are not available in most public datasets. We present a novel method to identify the cell-type composition, signatures and proportions per sample without need for a priori information. The method was successfully tested on controlled and semi-controlled datasets and performed as accurately as current methods that do require additional information. As such, this method enables the analysis of cell-type specific gene expression using existing large pools of publically available microarray datasets.

主权项

1. A method of identifying cell-type, signatures and proportions in a heterogeneous tissue sample that includes multiple cell types, comprising the steps of:
providing purified reference signatures for each of the cell types suspected to exist in the sample; obtaining an initial estimate of expression profiles for each cell-type; estimating the true number of cell types using the symmetric Kullback-Leibler divergence (SKLD) between each of the estimated cell-type profiles and the initial cell-type reference signatures, where the closest estimated profiles are then chosen as the final cell-type specific separated signatures; and computing the cell-type proportions per sample, using the method of non-negative least squares (NNLS).