Notes 20101116 BIOL 614 Seminars
From SnOwy - Ed's Wiki Notebook
Go through the readings for the presentations -- talks should be 20 to 30 minutes; discussions should end 30 to 40 minutes; 40 minutes is the hard maximum -- if possible send the slides the day before.
Contents |
Title: Using TESS to Predict Transcription Factor Binding Sites in DNA Sequences
Speaker: Anjuku
- TESS: Transcription element search system
- transcription factors
- using TESS / TESS results
- example application
TESS
- discovers transcription factor (TF) binding sites (BS)
- searches in forward or reverse
- TESS may detect many TF BS at high density (many are false)
- string models vs position weight matrix (PWM) models
- string model: describe consensus sequences as TF BS
- PWM: frequency matrix -- interesting, uses an information content measure
- TESS uses both models
- scoring schemes
- log likelihood -- has direct meaning for protein binding -- uses a threshold log likelihood for acceptance
- similarity scores -- two kinds: uses a consensus index -- penalties for mismatched sites
- alignments on the TF BS are evaluated with the above scoring schemes
- TRANSFAC alignments used
- string shorter than a threshold are not considered
- core: subsequence critical for binding
UI
- webserver
- either sequences or PWMs
- filter for specific transcription factors in the search
- filters by taxonomic hierarchy
- option to ignore non-core sites
- expert parameters ...
- determine how algorithm should handle ambiguous bases ...
Title: Why aren't humans venomous? Insights from the duck-billed platypus
Speaker: Owen Woody
- the honest question is -- why aren't more mammal species venomous?
- platypus draft genome recently submitted
- last surviving member of their genus
- monotreme
- sweating out milk instead of having nipples
- bill loaded with both mechano- and electro- receptors
- weird sex chromosome system
- females: ten X
- male: five X and five Y
- a bit like birds but not exactly (?)
- one of the few venomous animals
- venom spurs in hind limbs
- falls off in females, retained in mature males
- venom very potent, delivered forcefully -- can latch into target
- primary use? rival males
Venomics?
- venoms -- convergent evolution target
- same protein folds have been co-opted into becoming venomous convergently
- draft platypus genome draft complete
- not enough coverage to put into chromosomes -- some complete chromosomes
- the single platypus sequenced was a female -- no knowledge of the five Y chromosomes
- used conservative process to select candidate venoms
- 83 venom proteins across 13 families
- dogma of evolution -- things like this shouldn't happen this often
- could venoms be a common endpoint of evolution?
- so why are venoms so rare in mammals?
Red Queen Hypothesis
- warding off con-specific males?
- forced to keep innovating in order to keep up place in ecological niche?
- platypus is in an arms race with itself
- -- venom resistance set
- losing a single venom or venom resistance → instant fail
- the X chromosomes in the platypus don't map to the ones in other mammals
- appear to be autosomes that are cut up
Genome Alignment
- figure out where current chromosomes come from
- genome alignment can recover this history and find orthologues
- EGM tool
- compute distance matrix for all proteins in two genomes
- FASTA -- sequence ordered proteome
ConSURF
- finding homologous sites of conservation
- protein conserved sites contribute to function or structure
- two general approaches
- alignment of known sequences
- probabilistic mapping of protein surface
- conservation scores
- how is accuracy calculated?
