Title
Into the heart of darkness: large-scale clustering of human non-coding DNA.
Abstract
It is currently believed that the human genome contains about twice as much non-coding functional regions as it does protein-coding genes, yet our understanding of these regions is very limited.We examine the intersection between syntenically conserved sequences in the human, mouse and rat genomes, and sequence similarities within the human genome itself, in search of families of non-protein-coding elements. For this purpose we develop a graph theoretic clustering algorithm, akin to the highly successful methods used in elucidating protein sequence family relationships. The algorithm is applied to a highly filtered set of about 700 000 human-rodent evolutionarily conserved regions, not resembling any known coding sequence, which encompasses 3.7% of the human genome. From these, we obtain roughly 12 000 non-singleton clusters, dense in significant sequence similarities. Further analysis of genomic location, evidence of transcription and RNA secondary structure reveals many clusters to be significantly homogeneous in one or more characteristics. This subset of the highly conserved non-protein-coding elements in the human genome thus contains rich family-like structures, which merit in-depth analysis.Supplementary material to this work is available at http://www.soe.ucsc.edu/~jill/dark.html
Year
DOI
Venue
2004
10.1093/bioinformatics/bth946
ISMB/ECCB (Supplement of Bioinformatics)
Keywords
Field
DocType
human genome,rna secondary structure,large-scale clustering,rodent evolutionarily conserved region,non-protein-coding element,sequence similarity,in-depth analysis,significant sequence similarity,coding sequence,elucidating protein sequence family,human non-coding dna,syntenically conserved sequence,protein sequence
Genome,Conserved sequence,Conserved non-coding sequence,Genome project,Noncoding DNA,Biology,Comparative genomics,Bioinformatics,Human genome,Sequence analysis
Conference
Volume
Issue
ISSN
20 Suppl 1
1
1367-4811
Citations 
PageRank 
References 
3
1.17
9
Authors
3
Name
Order
Citations
PageRank
Gill Bejerano155163.30
David Haussler283273068.93
Mathieu Blanchette363162.65