Covariance in RNA
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Covariance in RNA ref " 1 72
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1 72. " ". Covariance in RNA. ref. Covariance. T y C. anticodon. 3’acc. D-stem. M ij = S fx i x j log 2 [fx i x j /(fx i fx j )] M=0 to 2 bits; x=base type x i x j see Durbin et al p. 266-8. Mutual Information. A CUUA U M 1,6 = S = fAU log 2 [fAU/(fA*fU)]... - PowerPoint PPT Presentation
Transcript of Covariance in RNA
Covariance
Mij= fxixjlog2[fxixj/(fxifxj)] M=0 to 2 bits; x=base type
xixj see Durbin et al p. 266-8.
D-stem
anticodonTC
3’acc
Mutual Information
ACUUAU M1,6= = fAU log2[fAU/(fA*fU)]...CCUUAG x1x6
GCUUGC =4*.25log2[.25/(.25*.25)]=2UCUUGAi=1 j=6 M1,2= 4*.25log2[.25/(.25*1)]=0
Mij= fxixjlog2[fxixj/(fxifxj)] M=0 to 2 bits; x=base type
xixj see Durbin et al p. 266-8.
See Shannon entropy, multinomial Grendar
trp/tyrA pair of genomes shows the best co-growth
Reppas, Lin & Church ; Shendure et al. Accurate Multiplex Polony Sequencing of an Evolved Bacterial Genome(2005) Science 309:1728
SecondPassage
First Passage
Covariance in lab evolution
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Q1
Q3
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EcNR1
Sequence monitoring of evolution(optimize transport & drug resistance)
Sequence
Reppas, Lin & Church
Co-evolution of mutual biosensors/biosynthesissequenced across time & within each time-point
Independent lines of Trp & Tyr co-culture
5 OmpF: (pore: large,hydrophilic > small)
42R-> G,L,C, 113 D->V, 117 E->A
2 Promoter: (cis-regulator) -12A->C, -35 C->A
5 Lrp: (trans-regulator) 1b, 9b, 8b, IS2 insert, R->L in
DBD.
Heterogeneity within each time-point . Shendure J, Porreca GJ, et al. 2005. Accurate multiplex polony sequencing of an evolved bacterial genome. Science 309: 1728-32
Flux ratios at each branch point yields optimal polymer composition for replication
x,y are two of the 100s of flux dimensions
Non-optimal evolves to optimal
Ibarra et al. Nature. 2002 Nov 14;420(6912):186-9. Escherichia coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growth.
Comparative genome sequencing of E. coli allows observation of bacterial evolution on a laboratory timescale.
Herring et al 2006 Nat. Gen 38:1406
The Amino-acid Mutational Spectrum of Human Genetic Disease.
Vitkup,D, Sander,C, Church,GM (2003) Genome Biol. 4: R72.
Prediction of deleterious
human alleles
Shamil Sunyaev, Vasily Ramensky, Ina Koch, Warren Lathe III, Alexey S. Kondrashov, and Peer Bork Hum Mol Genet (2001) 10: 591-597
http://genetics.bwh.harvard.edu/pph/http://polydoms.cchmc.org/polydoms/
Prediction Puzzles
>example1CACCCTCGCCAGTTACGAGCTGCCGAGCCGCTTCCTAGGCTCTCTGCGAATACGGACACGCATGCCACCCACAACAACTTTTTAAAAGAATCAGACGTGTGAAGGATTCTATTCGAATTACTTCTGCTCTCTGCTTTTATCACTTCACTGTGGGTCTGGGCGCGGGCTTTCTGCCAGCTCCGCGGACGCTGCCTTCGTCCAGCCGCAGAGGCCCCGCGGTCAGGGTCCCGCGTGCGGGGTACCGGGGGCAGAACCAGCGCGTGACCGGGGTCCGCGGTGCCGCAACGCCCCGGGTCTGCGCAGAGGCCCCTGCAGTCCCTGCCCGGCCCAGTCCGAGCTTCCCGGGCGGGCCCCCAGTCCGGCGATTTGCAGGAACTTTCCCCGGCGCTCCCACGCGAAGC
