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The construction of a complete EST-based gene index is an intricate task yet to be accomplished. GeneTide, the Gene Terra Incognita Discovery Endeavor (http://genecards.weizmann.ac.il/genetide/), which is the newest addition to the GeneCards suite of databases, comprehensively maps >4.5 of the ∼5.5 million human ESTs currently available at dbEST with either known or newly defined putative human genes. The association is accomplished via data mining genomic resources, and integrating using a unified scoring scheme. Groups of unassociated transcripts serve as a basis for defining EST-based gene candidates (EGCs). These EGCs are annotated with various parameters, including expression data, to determine their validity as possible de-novo genes. An immediate application of GeneTide to microarray annotation has increased, in a specific example, the number of annotated Affymetrix HGU95A-E probe sets by 50% in comparison to previous attempts.