Lecture 7
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Contents
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