Thursday, October 16, 2014

Day 2 and 3 Beyond Genome 2014

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
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.

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.
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
Talk1: Anchored Assembly: You can try at
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:
Guided visualization exploration of cancer genomics

Jian Ma

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