User:Robert M. MacCallum/WTFGSB Reportback
Welcome Trust Functional Genomics and Systems Biology Workshop
30 November to 1 December 2009
Day one
Edison Liu
Estrogen (or is it EGF) receptor (ER) binding site analysis (ChIP and bioinf) - "Cosmic" score, correlation with RNA PolII binding and H3K4meX marks.
Some functional binding is 1Mb away from gene!! Only 9% in 5k "promoter".
Cool ChIA-PET (ChiA-seq) method to determine chromosomal loops.
Looping for efficient transcription, grouping of coregulated genes ("looped out" genes don't respond to ER)
Johan Rung
GWAS for type 2 diabetes
F Pradezynski
Y2H between various virus proteomes and human proteins.
Many human pathways interfered with, in particular the ones you'd expect (interferon reponse)
Seems to be a remarkable number of targets (100s) from such a few viral proteins.
Chris Bakal
Wounding, cell morphology, image analysis -> 100+ feature profile of cell's, morphology.
"canalised" morphology space (jumps between states)
Keith Baggerly
Reproducibility in hi-thru biology
More to come on this
Nick Luscombe
Nuclear lamins known to tether transcriptionally inactive DNA
Nucleoporins now shown to be assoc with active gene expression.
Also through ChIP some proteins bind to enable X chromosome dosage compensation.
Mark Gerstein
A review of several years' network work. Including some Venter ocean sample sequence analysis (map to pathways, correlate with environmental factors with some canonical ..... method (is this like bi-clustering?))
Day two, session one
Seth Grant
Complexity of post-synaptic molecular machinery (several thousand proteins). Conserved in invertebrates (50% of prots) and single celled (25%). Evolution of the machinery (including plasticity) preceded evolution of synapses.
Very slow evolution.
Many diseases.
Caleb Webber
CNV in mouse
What's special about pathological CNVs? (vs. benign)
Human CNVs look up mouse phenotypes (somehow!)
Enrichment!
Florian Markowetz
ES cell histone modifications
days 1 3 5 of ES development - 4 analyses
Protein MS ChIP-chip histone Rna pol II Microarrays
day 0 nanog TF downreg -> network of TFs
clustering of smoothed histone profiles (around TSS)
when mRNA upreg, small local acetylation around TSS when mRNA down, wider deacetylation around TSS.
increased correlation between H acet and gene expression through time (more at day 5 than day 1) genome-wide
predict gene expr from histone acetylation using LOTS of ML methods (in R)
Grant Belgard
brain transcriptomics
by sequencing
6 layers of neocortex
many cell types spanning several layers
paired end 50bp reads
(you get some intronic reads)
some intergenic regions detected (a few percent of reads)
layer specific genes, various layers show various GO enrichments.
John Hogenesch
Circadian clock genes through hi-thru func genomics. nice robot video.
siRNA screen (seems to be tunable to desired knockdown level)
clock pathway is robust - surprising lack of lethal knock outs
Day two, session two
Peter Hoen
(standing in for Gert-Jan van Ommen)
Duchenne muscular dystrophy
antisense therapy
Andrew Teschendorff
classification of breast cancer
Dan Geschwind
transcriptional regulation of CNS development genes by FoxP2
looked at human vs chimp regulation of genes (microarray) in a cell line.
many genes respond differently (up and down)
But why? The 2 AA diffs are not in known DNA binding domain
6 genes regulated via proximal promoter (luciferase reporter)
validated in vivo
haNCS human accelerated non coding sequences (look this up)
Horvath weighted gene co-expression network analysis. WGCNA
Recent paper showing two mitochondrial network types in neurons (synaptic and cell body)
Compare human vs chimp networks
Douglas Kell
Suit and tie alert!
networks described in unambiguous fashion, SBML, ChEBI SMILES etc for small molecules.
uptake of drugs, via transporters (proteins).
Day two, session three
Genevieve Konopka
Language genes
Can't do multi-species (human, chimp, macaque) on a human affy chip.
Next gen sequencing! Four brain regions.
"Sequencing wins"
Networks from WGCNA
Tom Freeman
Networks in immunity
focus: macrophage
mentioned proteasome (did I see that on map wrt immunity?)
graphical markup for pathways
some kind of flow simulations through them
biolayout express software - looks good (has enrichment analysis built in)
Day two, session four
Frank Holstege
yeast
1200 regulatory components, TFs, kinases, ch remodelers, RNA processing -> mutations and expression microarrays
GASSCO dye correction algorithm (two colour!)
done so far deletome
some kinases have no diff expr, is it because they are inactive in standard conditions or is it because of redundancy?
The use some synthetic genetic interaction prediction to choose pairs
find signals!
some kinases redundant with phosphatase! it's cross talk between two pathways (somehow).
different types of redundancy:
- complete
- quantitative (double has more effect than single(s))
- incongruent (effects in single are not in double)
also used the data for protein complex prediction
Stefan Weimann
new targets for drug resistant breast cancer
ErbB signalling network
the drug is an ErbB2 antibody
Louis Serrano
Mycoplasma pneumoniae
689 ORFs + 44 RNAs
free living
maybe only 10-11 TFs (E. coli 100 or so)
full complement of chromatin remodelling
plan was to do loads of -omics + electron microscopy
transcriptomics: arrays 62 conditions, tiling array
detailed look at transcripts (reverse strand ncRNA, no idea of mechanism) multiple TSSs
where you have operons encoding 4 genes, you don't just see mRNA of all four, you get different levels of each gene, somehow...
same SOS response as subtilis, but without the TFs! very interesting
plenty of regulatory complexity
metabolome: KEGG didn't work out, had to do lots of manual work to build metabolic map. defined minimal medium.
know reactions are there, but 10-12 enzymes are not known
200 molecules per protein per cell
so small that you're "living in a stochastic world" - each reaction is like rolling a dice, how does it survive is an interesting question.