Lecture 7

From Colettapedia
Jump to navigation Jump to search

Eukaryotic (protists) Genomics

  • somewhere btw 1-1.5 billion years old

eukaryotic diversity

  • protists take up 90% of eukaryotic space
  • rhizaria
  • excavate
  • plant
  • chromalveolates
  • diplomonads should be "basal" branching
    • have nuclei
    • most have mitochondria
    • not animals, fungi, or plants

pathogens

  • chagas disease
  • african sleeping sickness
  • plasmodium falciparum
    • trades genes with all manner of things
    • tuberculosis
  • potato blight - phythoptera infestans - an oomycete
    • makes cell walls out of cellulose
  • EuPathDB - protist-specific Pathogen Database
  • GeneDB - more general (human) pathogen db

Mones Abu-Asab

  • high-throughput data - "industrial" data
  • but don't have tools
    • microarray
    • metabolomics
    • deep sequencing machines
  • use PCA
  • clustering
  • analytical methods not there
  • nee a way to synthesize data
    • how put together
  • what patterns exist in data
  • discover order in data
  • systems biology
    • the data - genotype
    • the disease - phenotype
    • evolutionary theory - (conceptual framework) - descent with change
  • carlo maley - in nature articel on cancer from evolutionary standpoint
      • cancer - evolutionary mistake
    • bioinformatics - analytical paradigm
  • need a predictive, seamless, multidimensional model - systems biology

unresolved issues

  • don't have a tool to study
  • disease modeling
  • mysery - early events that lead to cancer - what are the boundaries
  • biomarkers discovery
  • early detection

reason: heterogenous data

  • tumors can diversify and become heterogenous
    • imagine btween individual!
    • intratumao, intertumor, inter person
  • high mutation
  • high diversity of genen expression
  • multiple pathways
  • evolutionary
  • high mutation rate that is randomly generated
    • driver mutations versus passenger mutations
  • "I told you so"
  • are two types of cancers related? - besed on synapomorphies, shared derived charaacteristics
  • clade is a unit
    • apomorphy
    • synapomorphy
    • clade
    • cladogram
  • polarity assesment through outgroup comparison of each expression value into derived (diseased) or ancestral (normal)
  • maximum parsimomny

next

  • polarized values into 0 normal 1 derived
  • decide upfront whether expression level is normal abnormal, before dentrogram does it for you at the end
  • population biology genetics - keep adding specimens until variation stops.
  • polarity assesment = outgroup analysis
  • ex: dichotomously asynchronous expression
    • normal in the middle, cancerous outside, above and below expression, bimodal exporession
  • parsimony = ozzam's razor = principle of simplicity
    • cladogram that has the least number of steps
  • parsimony cladogram better than dendrogram based on pearson correllation
  • concordance - gene lists...?
  • by using phylogenetics, can figure out what is common between all cancers = BOUNDARIES
  • phylogenetics - early detection tool, find individuals accumulating change
  • a tool that can model disease!
  • no cancer material that's going to revert back to normal
  • metabolomics - the loweer part of the mas spec
  • does radiation return tissue to normal? noipe - cluster into its own group
  • healthy clades, transitional clades, cancer clade
  • tool for early detection, diagnosis, prognosis
  • direction of change, accumulation
  • cancer - cases of instant remission, cancer accumulated change that was disadvantageous to itself, nature of mutations are random
  • cancercer produces process of variation - to avoid tumor supressor genes
  • cancer selects for a mutation phenotype
  • communication between nucleus and mitochondria
  • mitochondrial