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ENCODE Pseudogenes and Transcription

This study identifies 211 pseudogenes in ENCODE regions using an updated computational pipeline and manual curation. The analysis compares Yale's pseudogenes with those from VEGA and ENSEMBL groups, revealing various classifications including processed, duplicated, and others. Notably, around 40% of these pseudogenes intersect with transcription activity, suggesting potential transcriptional relevance. The findings indicate weak correlations between gene and pseudogene numbers within these regions, with a significant association of non-unique transcriptional activity overlapping with pseudogenes.

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ENCODE Pseudogenes and Transcription

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  1. ENCODE Pseudogenes and Transcription Deyou Zheng Yale University 7-05-05, ENCODE-GT

  2. Yale 75 113 VEGA 40 23 ENSEMBL 2 9 Pseudogenes in ENCODE Regions • 211 pseudogenes were identified using an updated computational pipeline (Zhang et al. 2003) and manual curation. • Compare Yale pseudogenes with pseudogenes from VEGA group and the ENSEMBL group. 2

  3. Manually Picked (ENm*) Randomly Picked (ENr*) No. of Pseudogenes No. of Genes Break Down of Yale Pseudogenes r2=0.31 • More pseudogenes in the manually picked regions. • 211 Pseudogenes can be separated into 104 processed, 19 duplicated and 88 others. Others – those can’t be clearly binned to processed or duplicated, e.g., fragments. • Numbers of genes and pseudogenes are weakly correlated in ENCODE regions. 3

  4. Genes ENm004 Yale TARs using Oligo-microarray Affymetrix TARs using Oligo-microarray EST Intersection of Pseudogenes with Transcription Data Pseudogenes GIS-PET CAGE Transcription factors binding sites from ChIP-Chip Sequence conservation in rat, mouse and chimp 4

  5. Yale_Pgene_58 Example of a Pseudogene with Various Transcription Evidence 5

  6. Intersection of Pseudogenes with Transcription Data • By random chance, 20-30 Yale pseudogenes will intersect with TARs. • ~40% ENCODE pseudogenes intersect with TARs. So high percentage? 6

  7. Intersection of TARs with Pseudogenes Affy-Unique-TAR Yale-Unique-TAR No. of TARs Overlapping a Pseudogene Affy-not-Unique-TAR Yale-not-Unique-TAR No. of TARs • Not-”unique” TAR: one with a sequence of 60 bp (~3 probes) mapping to > 1 genomic locations (≥ 95% identity). 7 7

  8. Summary • 211 Pseudogenes (253, Yale + Vega) in ENCODE regions. • Some pseudogenes (< 7%) might be transcribed based on GIS-PET, CAGE or EST data. • About one half of pseudogenes overlap with TARs. • Non-unique TARs intersect with pseudogenes 5 times more often than unique TARs, probably due to cross-hybridization. • Comparison with previous analysis: • A more detailed survey found that 12-16% of chr22 pseudogenes intersected with TARs from tiling microarray (Zheng et al., 2005). • Both a chr22 and a whole genome analysis showed that ~5% human pseudogenes are likely transcribed (Zheng et al., 2005; Harrison et al., 2005). • Cheng et al. (2005) also reported that pseudogene-overlapping TARs are usually not unique. We repeat their analysis using ENCODE pseudogenes and find the same. • Refs: • Cheng et al., 2005, Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science. 308(5725): 1149-54. • Harrison et al., 2005, Transcribed processed pseudogenes in the human genome: an intermediate form of expressed retrosequence lacking protein-coding ability. Nucleic Acids Res. 33(8): 2374-83. • Zheng et al., 2005, Integrated pseudogene annotation for human chromosome 22: evidence for transcription. J Mol Biol. 349(1):27-45. 8

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