The GENCODE pseudogene resource

As part of the GENCODE annotation of the human genome, we present the first genome-wide pseudogene assignment for protein-coding genes, based on both large-scale manual annotation and in silico pipelines. A key aspect of this coupled approach is that it allows us to identify pseudogenes in an unbiased fashion as well as untangle complex events through manual evaluation. We integrate the pseudogene annotations with the extensive ENCODE functional genomics information. In particular, we determine the expression level, transcription-factor and RNA polymerase II binding, and chromatin marks associated with each pseudogene. Based on their distribution, we develop simple statistical models for each type of activity, which we validate with large-scale RT-PCR-Seq experiments. Finally, we compare our pseudogenes with conservation and variation data from primate alignments and the 1000 Genomes project, producing lists of pseudogenes potentially under selection.At one extreme, some pseudogenes possess conventional characteristics of functionality; these may represent genes that have recently died. On the other hand, we find interesting patterns of partial activity, which may suggest that dead genes are being resurrected as functioning non-coding RNAs. The activity data of each pseudogene are stored in an associated resource, psiDR, which will be useful for the initial identification of potentially functional pseudogenes.Pseudogenes are defined as defunct genomic loci with sequence similarity to functional genes but lacking coding potential due to the presence of disruptive mutations such as frame shifts and premature stop codons [1-4]. The functional paralogs of pseudogenes are often referred to as parent genes. Based on the mechanism of their creation, pseudogenes can be categorized into three large groups: (1) processed pseudogenes, created by retrotransposition of mRNA from functional protein-coding loci back into the genome; (2) duplicated (also referred to as unprocessed)