Talk 2: Genetics of
Gleoblastoma:
Different populations
are there in glioblastoma and fits to cancer stem cell model
Chipseq and functional
elements. In vitro model. Differentiated gleoblastoma cels . xenograft model.
Introduced TFS in vitro to induce tumor.
Core TFs bind to active
TPC regulatory elements
Single cell RNAseq for
glioblastoma. There is receptor diversity inside the glioblastoma tumor. 430
cells are sequenced. Each cell detected
around 6000 genes. PGFRA and TGFR are negatively co-regulated.
Core TFs are highly
co-related with stemness. Negative correlation with MES. Then classify cells
into high stemness or low stemness. For cells there is a dominant transcrion
signature. Cells can switch fromone subclass to another. Tumors are more
heterogenous than was thought before
--
Master regulators of
tumor initiation,progression…
SynGen algorithm for
predicting synergisim of molecules. ARACNe algorithm was used for
reconstructing genetic network.
--
Transcription profile:
regulatory network and functional network
LincsProject.org
Cell types,
perturbations and phenotypic assays.Cell types can be cancer cell lines, any
other cell lines, perturbations can be drug related. Assays can be transcriptomics,
proteomic. Lincs L1000 data (CMapIII). 22119 genetic reagents, 77 cellular
context, 20413 chemical reagents
--
Genomics, epigenomic…
Myc cell cycle, apoptosis, cellular transformation, cell proliferation.
Myc is over expressed in many cancers.
Drugging the cancer
interactions
Multifaceted target
assessment for druggability
Cncerdrug targets make
distinct subnetworks inside a network. Cansar.icr.ac.uk
--
A complete catalogue,
identification of drivers. Data sets are fewer for epigenetic data
modifications.
40epigenetic marks are
there
Understand the chromatin states between Normal->
Tumor -> Metastasis
Chipseq for 35 chromatin
marks. Generated a lot of data. Chromatin state prediction with ChromHMM
Relative changes in
chromatin marks.
Loss of acylation in tumorigenic
cells.
Six billion reads have
been generated. Epigenomic plasticity
--
Personalized medicine
BRAF is mutated in human
melanoma
Everolimus -> Has
17000 somatic mutation for a person who responded well.Map2k1 15 bp deletion.
EGFR BRAF MEK AKT mTORC1 Chemo
All the patients with
solid tumors have what kind of mutation needs to be determined before assessing
their treatment type.
341 genes are listed for
assay
--
Ten trillion bacterial
cells, ten times morebacteril cells human genes
100 times more number of
genes
--
Circulating tumor DNA.
Cell free DNA 90% are hematopoetic stem cells. Cell free DNA increases in
cancer patients.. Plasma-seq . The coverage is .1X depth
Grail is text mining
tool
--
Finding cancer driver
genes
Blair cell 2013
co-morbidity studies. 15cancers are there in TCGA hassomaticmutations.
Gain,mutated,loss.OMIM has germlinemutations. Genetic links network,pathways.
Cancer is co-morbid with
another genetic disease that happens due to mutation. Albinism is associated
with some common genes associated with melanoma.
1/3 of the medelian
disase have co-morbidity with ancer.
--
Bacterial-human somatic
lateral gene transfer for cancer.
Fourth chromosoma of
drosophila has 20% genome from bacteria.
--
Day 3
--
Bioinformatics
challenge:
BTG Informatics
challenge: Single cell Copy Number analysis
Baslan Nature protocol
2012
--
Visualizationofmulti
dimensionalcancer data Genome Medicine 2013
Copy number prediction
using Titan, Ha et al. Genome Research
2014
--
Genomic media
andclinical cancer medicine: Dana Faber Institute:
--
IGB
--
Guided visualization
exploration of cancer genomics
--
Jian Ma
No comments:
Post a Comment