Description
The consensus elements in this track were generated by the ENCODE Multi-Species
Analysis group from the nine different combinations of three conservation
algorithms (phastCons, binCons, and GERP) and three sequence alignment
methods (TBA, MLAGAN and MAVID) applied to the ENCODE region sequences
of
28 vertebrate species
as defined in the
September 2005 ENCODE MSA sequence freeze
and the
MSA species guide tree.
Three different stringencies were used.
The loose set of constrained
sequences represent bases identified as being constrained by any
conservation algorithm on any alignment. The moderate set of
constrained sequences is derived from bases shown to be constrained by
at least two of the three conservation algorithms on at least two of
the three alignments. Finally, the strict set of constrained
sequences represent only those bases that were constrained using all
three conservation programs on all three multi-sequence alignments.
Display Conventions and Configuration
The locations of constrained elements are indicated by blocks in the graphical
display. To show only selected subtracks within this annotation,
uncheck the boxes next to the tracks you wish to hide.
Methods
See the description pages for the TBA Elements,
MLAGAN Elements and
MAVID Elements
for additional information about methods used to generate these data.
Verification
See the description pages for the TBA Elements, MLAGAN Elements
and MAVID Elements
for information about verification techniques used to generate these data.
Credits
The strict, moderate, and loose data shown in these subtracks were
contributed by Elliott Margulies of NHGRI representing the ENCODE Multi-Species
Analysis group.
Conservation Scoring
PhastCons was developed by
Adam Siepel,
Cold Spring Harbor Laboratory, while at the
Haussler Lab at UCSC.
BinCons was developed by Elliott Margulies, while at the
Eric Green lab.
GERP
was developed primarily by Greg Cooper in the lab of
Arend Sidow
at Stanford University (Depts of Pathology and Genetics), in close collaboration
with Eric Stone (Biostatistics, NC State), and George Asimenos and
Eugene Davydov in the lab of
Serafim Batzoglou
(Dept. of Computer Science, Stanford).
Sequence Alignment
TBA and Blastz were developed by Minmei Hou, Scott Schwartz and Webb Miller of the
Penn State Bioinformatics
Group.
MLAGAN,
Shuffle-LAGAN, and SuperMap were written by Mike Brudno
while at the Batzoglou lab.
MUSCLE
was authored by Bob Edgar.
AB-BLAST
was provided by the
Gish lab
at the School of Medicine, University of Washington in St. Louis.
Mercator
was written by Colin Dewey and Lior Pachter at the
Pachter Lab Comparative Genomics Group at UC Berkeley.
MAVID
was authored by Nicholas Bray and Lior Pachter.
The phylogenetic tree is based on
Murphy et al. (2001)
and general consensus in the vertebrate phylogeny community.
References
Blanchette, M., Kent, W.J., Reimer, C., Elnitski, L., Smit, A.,
Roskin, K., Baertsch, R., Rosenbloom, K.R., Clawson, H. et al.
Aligning Multiple Genomic Sequences With the Threaded Blockset
Aligner.
Genome Res 14(4), 708-15 (2004).
Bray, N. and Pachter, L.
MAVID: Constrained Ancestral Alignment of Multiple Sequences.
Genome Res 14(4), 693-99 (2004).
Brudno, M., Do, C., Cooper, G., Kim, M.F., Davydov, E., NISC Comparative
Sequencing Program, Green, E.D., Sidow, A. and Batzoglou, S.
LAGAN and Multi-LAGAN: efficient tools for large-scale multiple
alignment of genomic DNA.
Genome Res 13(4), 721-31 (2003).
Brudno, M., Malde, S., Poliakov, A., Do, C., Couronne, O., Dubchak, I. and
Batzoglou, S.
Global alignment: finding rearrangements during alignment.
Bioinformatics 19(Suppl. 1), i54-i62 (2003).
Burge, C. and Karlin, S.
Prediction of complete gene structures in human genomic DNA.
J Mol Biol 268(1), 78-94 (1997).
Chiaromonte, F., Yap, V.B., and Miller, W.
Scoring pairwise genomic sequence alignments.
Pac Symp Biocomput, 115-26 (2002).
Cooper, G.M., Stone, E.A., Asimenos, G., NISC Comparative Sequencing Program,
Green, E.D., Batzoglou, S. and Sidow, A.
Distribution and intensity of constraint in mammalian genomic
sequence.
Genome Res 15(7), 901-13 (2005).
Dewey, C.N. and Pachter, L.
Mercator: multiple whole-genome orthology map construction.
In preparation.
Edgar, R.C.
MUSCLE: multiple sequence alignment with high
accuracy and high throughput.
Nucl Acids Res 32(5), 1792-97 (2004).
Kent, W.J.
BLAT-the BLAST-like alignment tool.
Genome Res 12(4), 656-664 (2002).
Kurtz, S., Phillippy, A., Delcher, A.L., Smoot, M., Shumway, M., Antonescu, C.
and Salzberg, S.L.
Versatile and open software for comparing large genomes.
Genome Biol 5(2), R12 (2004).
Margulies, E.H., Blanchette, M., NISC Comparative Sequencing Program,
Haussler, D. and Green, E.D.
Identification and characterization of multi-species conserved
sequences.
Genome Res 13(12), 2507-18 (2003).
Murphy, W.J., et al.
Resolution of the early placental mammal radiation using Bayesian phylogenetics. Science 294(5550), 2348-51 (2001).
Schwartz, S., Kent, W.J., Smit, A., Zhang, Z., Baertsch, R., Hardison, R.,
Haussler, D. and Miller, W.
Human-Mouse Alignments with BLASTZ.
Genome Res 13(1), 103-7 (2003).
Siepel, A., Bejerano, G., Pedersen, J.S., Hinrichs, A., Hou, M.,
Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L.W. et al.
Evolutionarily conserved elements in vertebrate,
insect, worm, and yeast genomes.
Genome Res 15(8), 1034-50 (2005).
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