Automated whole-genome multiple alignment of rat, mouse, and human.
We have built a whole-genome multiple alignment of the three currently available mammalian genomes using a fully automated pipeline that combines the local/global approach of the Berkeley Genome Pipeline and the LAGAN program. The strategy is based on progressive alignment and consists of two main steps: (1) alignment of the mouse and rat genomes, and (2) alignment of human to either the mouse-rat alignments from step 1, or the remaining unaligned mouse and rat sequences. The resulting alignments demonstrate high sensitivity, with 87% of all human gene-coding areas aligned in both mouse and rat. The specificity is also high: <7% of the rat contigs are aligned to multiple places in human, and 97% of all alignments with human sequence >100 kb agree with a three-way synteny map built independently, using predicted exons in the three genomes. At the nucleotide level <1% of the rat nucleotides are mapped to multiple places in the human sequence in the alignment, and 96.5% of human nucleotides within all alignments agree with the synteny map. The alignments are publicly available online, with visualization through the novel Multi-VISTA browser that we also present.
Brudno
Michael
M
Department of Computer Science, Stanford University, Stanford, California 94305, USA.
Poliakov
Alexander
A
Salamov
Asaf
A
Cooper
Gregory M
GM
Sidow
Arend
A
Rubin
Edward M
EM
Solovyev
Victor
V
Batzoglou
Serafim
S
Dubchak
Inna
I
D000818:Animals; D001331:Automation; D019295:Computational Biology / Q000379:methods / Q000639:trends; D005091:Exons / Q000235:genetics; D016678:Genome; D015894:Genome, Human; D006801:Humans; D051379:Mice; D020161:Physical Chromosome Mapping / Q000379:methods / Q000639:trends; D051381:Rats; D016415:Sequence Alignment / Q000379:methods* / Q000592:standards / Q000639:trends*; D012984:Software; D026801:Synteny / Q000235:genetics