Distinguishing regulatory DNA from neutral sites.

Genome Res 2003 Jan;13(1):64-72

Departments of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.

We explore several computational approaches to analyzing interspecies genomic sequence alignments, aiming to distinguish regulatory regions from neutrally evolving DNA. Human-mouse genomic alignments were collected for three sets of human regions: (1) experimentally defined gene regulatory regions, (2) well-characterized exons (coding sequences, as a positive control), and (3) interspersed repeats thought to have inserted before the human-mouse split (a good model for neutrally evolving DNA). Models that potentially could distinguish functional noncoding sequences from neutral DNA were evaluated on these three data sets, as well as bulk genome alignments. Our analyses show that discrimination based on frequencies of individual nucleotide pairs or gaps (i.e., of possible alignment columns) is only partially successful. In contrast, scoring procedures that include the alignment context, based on frequencies of short runs of alignment columns, dramatically improve separation between regulatory and neutral features. Such scoring functions should aid in the identification of putative regulatory regions throughout the human genome.

Download full-text PDF

Source
http://www.genome.org/cgi/doi/10.1101/gr.817703
Publisher Site
http://dx.doi.org/10.1101/gr.817703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC430974PMC
January 2003
13 Reads

Publication Analysis

Top Keywords

regulatory regions
12
based frequencies
8
neutrally evolving
8
evolving dna
8
alignment columns
8
short runs
4
split good
4
runs alignment
4
distinguish functional
4
human-mouse split
4
model neutrally
4
models distinguish
4
inserted human-mouse
4
dna models
4
frequencies short
4
good model
4
columns dramatically
4
partially successful
4
sequences positive
4
coding sequences
4

Similar Publications