building synteny maps recommended local aligners blastz most accurate, especially for genes chains...
Post on 21-Dec-2015
219 views
TRANSCRIPT
![Page 1: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/1.jpg)
Building synteny maps
Recommended local aligners• BLASTZ
Most accurate, especially for genes Chains local alignments
• WU-BLAST Good tradeoff of efficiency/sensitivity Best command-line options
• BLAT Fast, less sensitive Good for
• comparing very similar sequences • finding rough homology map
![Page 2: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/2.jpg)
Index-based local alignment
Dictionary:
All words of length k (~10)
Alignment initiated between words of alignment score T
(typically T = k)
Alignment:
Ungapped extensions until score
below statistical threshold
Output:
All local alignments with score
> statistical threshold
……
……
query
DB
query
scan
Question: Using an idea from overlap detection, better way to find all local alignments between two genomes?
![Page 3: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/3.jpg)
Local Alignments
![Page 4: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/4.jpg)
After chaining
![Page 5: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/5.jpg)
Chaining local alignments
1. Find local alignments
2. Chain -O(NlogN) L.I.S.
3. Restricted DP
![Page 6: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/6.jpg)
Progressive Alignment
• When evolutionary tree is known:
Align closest first, in the order of the tree In each step, align two sequences x, y, or profiles px, py, to generate a new
alignment with associated profile presult
Weighted version: Tree edges have weights, proportional to the divergence in that edge New profile is a weighted average of two old profiles
x
w
y
z
Example
Profile: (A, C, G, T, -)px = (0.8, 0.2, 0, 0, 0)py = (0.6, 0, 0, 0, 0.4)
s(px, py) = 0.8*0.6*s(A, A) + 0.2*0.6*s(C, A) + 0.8*0.4*s(A, -) + 0.2*0.4*s(C, -)
Result: pxy = (0.7, 0.1, 0, 0, 0.2)
s(px, -) = 0.8*1.0*s(A, -) + 0.2*1.0*s(C, -)
Result: px- = (0.4, 0.1, 0, 0, 0.5)
![Page 7: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/7.jpg)
Threaded Blockset Aligner
Human–Cow
HMR – CDRestricted AreaProfile Alignment
![Page 8: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/8.jpg)
Reconstructing the Ancestral Mammalian Genome
Human: C
Baboon: C
Cat: C
Dog: G
C
C or G
G
![Page 9: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/9.jpg)
Neutral Substitution Rates Dataset 3: 4-D sites
![Page 10: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/10.jpg)
Finding Conserved Elements (1)
• Binomial method 25-bp window in the human genome Binomial distribution of k matches in N bases given the neutral
probability of substitution
![Page 11: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/11.jpg)
Finding Conserved Elements (2)
• Parsimony Method Count minimum # of mutations explaining each column Assign a probability to this parsimony score given neutral model Multiply probabilities across 25-bp window of human genome
A
CAAG
![Page 12: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/12.jpg)
Finding Conserved Elements
![Page 13: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/13.jpg)
Finding Conserved Elements (3)
GERP
![Page 14: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/14.jpg)
Phylo HMMs
HMM
Phylogenetic Tree Model
Phylo HMM
![Page 15: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/15.jpg)
Finding Conserved Elements (3)
![Page 16: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/16.jpg)
How do the methods agree/disagree?
![Page 17: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/17.jpg)
Statistical Power to Detect Constraint
L
N
C: cutoff # mutationsD: neutral mutation rate: constraint mutation rate relative to neutral
![Page 18: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/18.jpg)
Statistical Power to Detect Constraint
L
N
C: cutoff # mutationsD: neutral mutation rate: constraint mutation rate relative to neutral
![Page 19: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/19.jpg)
TTATATTGAATTTTCAAAAATTCTTACTTTTTTTTTGGATGGACGCAAAGAAGTTTAATAATCATATTACATGGCATTACCACCATATACATATCCATATCTAATCTTACTTATATGTTGTGGAAATGTAAAGAGCCCCATTATCTTAGCCTAAAAAAACCTTCTCTTTGGAACTTTCAGTAATACGCTTAACTGCTCATTGCTATATTGAAGTACGGATTAGAAGCCGCCGAGCGGGCGACAGCCCTCCGACGGAAGACTCTCCTCCGTGCGTCCTCGTCTTCACCGGTCGCGTTCCTGAAACGCAGATGTGCCTCGCGCCGCACTGCTCCGAACAATAAAGATTCTACAATACTAGCTTTTATGGTTATGAAGAGGAAAAATTGGCAGTAACCTGGCCCCACAAACCTTCAAATTAACGAATCAAATTAACAACCATAGGATGATAATGCGATTAGTTTTTTAGCCTTATTTCTGGGGTAATTAATCAGCGAAGCGATGATTTTTGATCTATTAACAGATATATAAATGGAAAAGCTGCATAACCACTTTAACTAATACTTTCAACATTTTCAGTTTGTATTACTTCTTATTCAAATGTCATAAAAGTATCAACAAAAAATTGTTAATATACCTCTATACTTTAACGTCAAGGAGAAAAAACTATAATGACTAAATCTCATTCAGAAGAAGTGATTGTACCTGAGTTCAATTCTAGCGCAAAGGAATTACCAAGACCATTGGCCGAAAAGTGCCCGAGCATAATTAAGAAATTTATAAGCGCTTATGATGCTAAACCGGATTTTGTTGCTAGATCGCCTGGTAGAGTCAATCTAATTGGTGAACATATTGATTATTGTGACTTCTCGGTTTTACCTTTAGCTATTGATTTTGATATGCTTTGCGCCGTCAAAGTTTTGAACGATGAGATTTCAAGTCTTAAAGCTATATCAGAGGGCTAAGCATGTGTATTCTGAATCTTTAAGAGTCTTGAAGGCTGTGAAATTAATGACTACAGCGAGCTTTACTGCCGACGAAGACTTTTTCAAGCAATTTGGTGCCTTGATGAACGAGTCTCAAGCTTCTTGCGATAAACTTTACGAATGTTCTTGTCCAGAGATTGACAAAATTTGTTCCATTGCTTTGTCAAATGGATCATATGGTTCCCGTTTGACCGGAGCTGGCTGGGGTGGTTGTACTGTTCACTTGGTTCCAGGGGGCCCAAATGGCAACATAGAAAAGGTAAAAGAAGCCCTTGCCAATGAGTTCTACAAGGTCAAGTACCCTAAGATCACTGATGCTGAGCTAGAAAATGCTATCATCGTCTCTAAACCAGCATTGGGCAGCTGTCTATATGAATTAGTCAAGTATACTTCTTTTTTTTACTTTGTTCAGAACAACTTCTCATTTTTTTCTACTCATAACTTTAGCATCACAAAATACGCAATAATAACGAGTAGTAACACTTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCACAAACTTTAAAACACAGGGACAAAATTCTTGATATGCTTTCAACCGCTGCGTTTTGGATACCTATTCTTGACATGATATGACTACCATTTTGTTATTGTACGTGGGGCAGTTGACGTCTTATCATATGTCAAAG...TTGCGAAGTTCTTGGCAAGTTGCCAACTGACGAGATGCAGTAACACTTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCACAAACTTTAAAACACAGGGACAAAATTCTTGATATGCTTTCAACCGCTGCGTTTTGGATACCTATTCTTGACATGATATGACTACCATTTTGTTATTGTACGTGGGGCAGTTGACGTCTTATCATATGTCAAAGTCATTTGCGAAGTTCTTGGCAAGTTGCCAACTGACGAGATGCAGTTTCCTACGCATAATAAGAATAGGAGGGAATATCAAGCCAGACAATCTATCATTACATTTAAGCGGCTCTTCAAAAAGATTGAACTCTCGCCAACTTATGGAATCTTCCAATGAGACCTTTGCGCCAAATAATGTGGATTTGGAAAAAGAGTATAAGTCATCTCAGAGTAATATAACTACCGAAGTTTATGAGGCATCGAGCTTTGAAGAAAAAGTAAGCTCAGAAAAACCTCAATACAGCTCATTCTGGAAGAAAATCTATTATGAATATGTGGTCGTTGACAAATCAATCTTGGGTGTTTCTATTCTGGATTCATTTATGTACAACCAGGACTTGAAGCCCGTCGAAAAAGAAAGGCGGGTTTGGTCCTGGTACAATTATTGTTACTTCTGGCTTGCTGAATGTTTCAATATCAACACTTGGCAAATTGCAGCTACAGGTCTACAACTGGGTCTAAATTGGTGGCAGTGTTGGATAACAATTTGGATTGGGTACGGTTTCGTTGGTGCTTTTGTTGTTTTGGCCTCTAGAGTTGGATCTGCTTATCATTTGTCATTCCCTATATCATCTAGAGCATCATTCGGTATTTTCTTCTCTTTATGGCCCGTTATTAACAGAGTCGTCATGGCCATCGTTTGGTATAGTGTCCAAGCTTATATTGCGGCAACTCCCGTATCATTAATGCTGAAATCTATCTTTGGAAAAGATTTACAATGATTGTACGTGGGGCAGTTGACGTCTTATCATATGTCAAAGTCATTTGCGAAGTTCTTGGCAAGTTGCCAACTGACGAGATGCAGTAACACTTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCACAAACTTTAAAACACAGGGACAAAATTCTTGATATGCTTTCAACCGCTGCGTTTTGGATACCTATTCTTGACATGATATGACTACCATTTTGTTATTGTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAAT
![Page 20: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/20.jpg)
TTATATTGAATTTTCAAAAATTCTTACTTTTTTTTTGGATGGACGCAAAGAAGTTTAATAATCATATTACATGGCATTACCACCATATACATATCCATATCTAATCTTACTTATATGTTGTGGAAATGTAAAGAGCCCCATTATCTTAGCCTAAAAAAACCTTCTCTTTGGAACTTTCAGTAATACGCTTAACTGCTCATTGCTATATTGAAGTACGGATTAGAAGCCGCCGAGCGGGCGACAGCCCTCCGACGGAAGACTCTCCTCCGTGCGTCCTCGTCTTCACCGGTCGCGTTCCTGAAACGCAGATGTGCCTCGCGCCGCACTGCTCCGAACAATAAAGATTCTACAATACTAGCTTTTATGGTTATGAAGAGGAAAAATTGGCAGTAACCTGGCCCCACAAACCTTCAAATTAACGAATCAAATTAACAACCATAGGATGATAATGCGATTAGTTTTTTAGCCTTATTTCTGGGGTAATTAATCAGCGAAGCGATGATTTTTGATCTATTAACAGATATATAAATGGAAAAGCTGCATAACCACTTTAACTAATACTTTCAACATTTTCAGTTTGTATTACTTCTTATTCAAATGTCATAAAAGTATCAACAAAAAATTGTTAATATACCTCTATACTTTAACGTCAAGGAGAAAAAACTATAATGACTAAATCTCATTCAGAAGAAGTGATTGTACCTGAGTTCAATTCTAGCGCAAAGGAATTACCAAGACCATTGGCCGAAAAGTGCCCGAGCATAATTAAGAAATTTATAAGCGCTTATGATGCTAAACCGGATTTTGTTGCTAGATCGCCTGGTAGAGTCAATCTAATTGGTGAACATATTGATTATTGTGACTTCTCGGTTTTACCTTTAGCTATTGATTTTGATATGCTTTGCGCCGTCAAAGTTTTGAACGATGAGATTTCAAGTCTTAAAGCTATATCAGAGGGCTAAGCATGTGTATTCTGAATCTTTAAGAGTCTTGAAGGCTGTGAAATTAATGACTACAGCGAGCTTTACTGCCGACGAAGACTTTTTCAAGCAATTTGGTGCCTTGATGAACGAGTCTCAAGCTTCTTGCGATAAACTTTACGAATGTTCTTGTCCAGAGATTGACAAAATTTGTTCCATTGCTTTGTCAAATGGATCATATGGTTCCCGTTTGACCGGAGCTGGCTGGGGTGGTTGTACTGTTCACTTGGTTCCAGGGGGCCCAAATGGCAACATAGAAAAGGTAAAAGAAGCCCTTGCCAATGAGTTCTACAAGGTCAAGTACCCTAAGATCACTGATGCTGAGCTAGAAAATGCTATCATCGTCTCTAAACCAGCATTGGGCAGCTGTCTATATGAATTAGTCAAGTATACTTCTTTTTTTTACTTTGTTCAGAACAACTTCTCATTTTTTTCTACTCATAACTTTAGCATCACAAAATACGCAATAATAACGAGTAGTAACACTTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCACAAACTTTAAAACACAGGGACAAAATTCTTGATATGCTTTCAACCGCTGCGTTTTGGATACCTATTCTTGACATGATATGACTACCATTTTGTTATTGTACGTGGGGCAGTTGACGTCTTATCATATGTCAAAG...TTGCGAAGTTCTTGGCAAGTTGCCAACTGACGAGATGCAGTAACACTTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCACAAACTTTAAAACACAGGGACAAAATTCTTGATATGCTTTCAACCGCTGCGTTTTGGATACCTATTCTTGACATGATATGACTACCATTTTGTTATTGTACGTGGGGCAGTTGACGTCTTATCATATGTCAAAGTCATTTGCGAAGTTCTTGGCAAGTTGCCAACTGACGAGATGCAGTTTCCTACGCATAATAAGAATAGGAGGGAATATCAAGCCAGACAATCTATCATTACATTTAAGCGGCTCTTCAAAAAGATTGAACTCTCGCCAACTTATGGAATCTTCCAATGAGACCTTTGCGCCAAATAATGTGGATTTGGAAAAAGAGTATAAGTCATCTCAGAGTAATATAACTACCGAAGTTTATGAGGCATCGAGCTTTGAAGAAAAAGTAAGCTCAGAAAAACCTCAATACAGCTCATTCTGGAAGAAAATCTATTATGAATATGTGGTCGTTGACAAATCAATCTTGGGTGTTTCTATTCTGGATTCATTTATGTACAACCAGGACTTGAAGCCCGTCGAAAAAGAAAGGCGGGTTTGGTCCTGGTACAATTATTGTTACTTCTGGCTTGCTGAATGTTTCAATATCAACACTTGGCAAATTGCAGCTACAGGTCTACAACTGGGTCTAAATTGGTGGCAGTGTTGGATAACAATTTGGATTGGGTACGGTTTCGTTGGTGCTTTTGTTGTTTTGGCCTCTAGAGTTGGATCTGCTTATCATTTGTCATTCCCTATATCATCTAGAGCATCATTCGGTATTTTCTTCTCTTTATGGCCCGTTATTAACAGAGTCGTCATGGCCATCGTTTGGTATAGTGTCCAAGCTTATATTGCGGCAACTCCCGTATCATTAATGCTGAAATCTATCTTTGGAAAAGATTTACAATGATTGTACGTGGGGCAGTTGACGTCTTATCATATGTCAAAGTCATTTGCGAAGTTCTTGGCAAGTTGCCAACTGACGAGATGCAGTAACACTTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCACAAACTTTAAAACACAGGGACAAAATTCTTGATATGCTTTCAACCGCTGCGTTTTGGATACCTATTCTTGACATGATATGACTACCATTTTGTTATTGTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATTT
Promoter motifs
3’ UTR motifs
Exons
Introns
![Page 21: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/21.jpg)
Comparing genomes reveals functional elements
• Ultra-conserved elements
• Protein-coding genes
• Short regulatory motifs
![Page 22: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/22.jpg)
ATGACTAAATCTCATTCAGAAGAAGTGA
Regulatory Motif Discovery
GAL1
CCCCWCGG CCG
Gal4 Mig1
CGG CCG
Gal4
• Gene regulation Genes are turned on / off in response to changing environments Gene regulatory logic is controlled by sequence motifs Specialized proteins (transcription factors) recognize motifs
• What makes motif discovery hard? Motifs are short (6-8 bp) and usually degenerate Act at variable distances upstream (or downstream) of target gene
![Page 23: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/23.jpg)
Overview of Motif Discovery Algorithms
![Page 24: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/24.jpg)
Motif Representation
GTATAACTATAAGTCTTAATATACGTAATATTGTACGTATTAGTATTCATCTAA
GTATAACTATAAGTCTTAATATACGTAATATTGTACGTATTAGTATTCATCTAA
PSSMPSSM
GTATAAGTATAA
ConsensusConsensus
GTATAMGTATAM
IUPACIUPAC
Complex Dependency
Graphical Models
Complex Dependency
Graphical Models
GTATAAGTATAA
CTATAACTATAA
TTGTACTTGTACGTCTTAGTCTTA
GTAATAGTAATAATATACATATAC
GTATTAGTATTA
GTATTCGTATTC
ATCTAAATCTAA
Nonparametric –
Graph or Bag of Words
Nonparametric –
Graph or Bag of Words
![Page 25: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/25.jpg)
Motif Representation – Pairwise Dependencies
Complex Dependency
Graphical Models
Complex Dependency
Graphical Models
![Page 26: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/26.jpg)
Motif Representation – MotifScan
GTATAAGTATAA
CTATAACTATAA
TTGTACTTGTACGTCTTAGTCTTA
GTAATAGTAATAATATACATATAC
GTATTAGTATTA
GTATTCGTATTC
ATCTAAATCTAA
![Page 27: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/27.jpg)
![Page 28: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/28.jpg)
![Page 29: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/29.jpg)
![Page 30: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/30.jpg)
![Page 31: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/31.jpg)
![Page 32: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/32.jpg)
![Page 33: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/33.jpg)
![Page 34: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/34.jpg)
![Page 35: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/35.jpg)
![Page 36: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/36.jpg)
![Page 37: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/37.jpg)
![Page 38: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/38.jpg)
![Page 39: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/39.jpg)
![Page 40: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/40.jpg)
![Page 41: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/41.jpg)
![Page 42: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/42.jpg)
![Page 43: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/43.jpg)
![Page 44: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/44.jpg)
![Page 45: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/45.jpg)
![Page 46: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/46.jpg)
![Page 47: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/47.jpg)
![Page 48: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/48.jpg)
![Page 49: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/49.jpg)
![Page 50: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/50.jpg)
![Page 51: Building synteny maps Recommended local aligners BLASTZ Most accurate, especially for genes Chains local alignments WU-BLAST Good tradeoff of efficiency/sensitivity](https://reader033.vdocuments.net/reader033/viewer/2022051401/56649d6c5503460f94a4c78e/html5/thumbnails/51.jpg)