Meissner: When genes get turned off - H3K27me3 promoters. Preimplantation - global depletion. Most CpGs unmeth. #AGBT18
9:35am February 14th 2018 via Hootsuite
Meissner: Dereg of DNMT1, 3A, 3B is linked to many human diseases. Any somatic cell: a bimodal dist. CpG islands unmethylated #AGBT18
9:33am February 14th 2018 via Hootsuite
Meissner: Starts by showing difference between C and 5-meC. No change in base pairing or coding function. Essential for dev #AGBT18
9:32am February 14th 2018 via Hootsuite
Alex Meissner (Max Planck Inst Germany) Mammalian DNA methylation landscapes and cancer #AGBT18
Nobrega: Model: SNP causes up-reg of TCF7L2, block adipogenesis, fewer cells -> insensitive to insulin. Pleiotropism, gene x env #AGBT18
9:28am February 14th 2018 via Hootsuite
Nobrega: Now w/Tcf7l2 over-exp mice, cross w/mice to get fat-specific prevented over-expression. Data suggest: adipogenesis defect #AGBT18
9:20am February 14th 2018 via Hootsuite
Nobrega: Shows the SNP confers allele-spec enhancer activity across beta cells, enterocytes, adipocytes. 1 bp difference. #AGBT18
9:16am February 14th 2018 via Hootsuite
Nobrega: Is rs7903146 within a tissue-specific enhancer? Answer: w/in pancreatic islets, enteroendocrine cells, adipocytes #AGBT18
9:15am February 14th 2018 via Hootsuite
Nobrega: #AGBT18 '14 ref for PMCA for conserved TF binding sites, module, inferred etc https://t.co/hxZayFTsNo
9:14am February 14th 2018 via Hootsuite
Nobrega: TCF7L2 function not in pancreas but in other tissues are poorly characterized. Phyogenetic module complex analysis PMCA #AGBT18
9:13am February 14th 2018 via Hootsuite
Nobrega: Diabetes community focus on the pancreas; he wants to move beyond it '13 commentary https://t.co/ijNUEI1MvV #AGBT18
9:12am February 14th 2018 via Hootsuite
Nobrega: Now human exh put into mice, driving RNA expression data shown. But mouse become diabetic - a dose-response. #AGBT18
9:10am February 14th 2018 via Hootsuite
Nobrega: Shoes Tcf7l2+/- mice have better glucose tolerance, protect against T2D. Took a human BAC w/enhancer driving expression... #AGBT18
9:09am February 14th 2018 via Hootsuite
Nobrega: Mice w/in vivo copy number allelic series - from 0 to 8; Tcf7l2-/- mice die w/in hours w/hypoglycemia. Grad students watch! #AGBT18
Nobrega: Region of assocn for TCF7L2: 250kb upstream, transgenetic mice w/reporter; if deleted all expression lost b/c of this area #AGBT18
9:08am February 14th 2018 via Hootsuite
Nobrega: Regulatory elements: 10-15% are in the closest promoter. 50% are 5+ genes away. #AGBT18
9:06am February 14th 2018 via Hootsuite
Nobrega: Looking at TCF7L2 in T2D risk '10 ref https://t.co/FI7XfoZzH9 proximity isn't indicative of gene/enh interactions #AGBT18
9:05am February 14th 2018 via Hootsuite
Nobrega: Also establish causal varient, and then infer phenotypic consequences (at the molecular, cellular or whole system level) #AGBT18
9:04am February 14th 2018 via Hootsuite
Nobrega: Promises of GWAS: new disease genes, mech/pathways, and Rx targets. Challenges: ID target assoc gene, relevant tissue... #AGBT18
9:03am February 14th 2018 via Hootsuite
Nobrega: Alt title: "Regulatory genetic variation and human disease" #AGBT18
9:02am February 14th 2018 via Hootsuite
Marcel Nobrega (Univ Chicago IL) Emerging challenges in complex traits: one locus, multiple variants, genes, and tissues #AGBT18
9:01am February 14th 2018 via Hootsuite
Omics! Omics!: #AGBT18 10X Previews Three New Single Cell Applications https://t.co/nxbqWTeYsC
8:24am February 14th 2018 via Hootsuite
RT @coregenomics: I just updated the following post: New products from @10XGenomics #AGBT18 workshop https://t.co/scGu0DQ2LJ
8:19am February 14th 2018 via Hootsuite
Something I thought I’d never see as a former LifeTech / Ion Torrent dude. #AGBT18 https://t.co/tb0vFgIwM7
8:18am February 14th 2018 via Hootsuite
RT @TorontoGenomics: The @illumina iSeq is a 4M read sequencer by spec. Single use cartridge with CMOS detection and a one dye chemistry.…
8:17am February 14th 2018 via Hootsuite
RT @TorontoGenomics: Illumina: One colour chemisty. G - no fluor T - has a fluor A - cleavable fluor C - dye added after incorporation.…
8:16am February 14th 2018 via Hootsuite
Q: Comment on FISH FP? Costa: Retried but could not reproduce FISH result (by FISH) #AGBT18
9:29pm February 13th 2018 via Hootsuite
Q: Failure rate and mode of samples? Costa: Samples were relatively recent. Oldest from 2014. #AGBT18
9:28pm February 13th 2018 via Hootsuite
Q: With NGS of data, can get other info from dataset? Costa: Only proof of principle. Deep - 50M-100M reads/sample. Can call SNVs #AGBT18
9:26pm February 13th 2018 via Hootsuite
Costa: Showed the dot plots of 3 sample results. #AGBT18
9:25pm February 13th 2018 via Hootsuite
@chenghlee Now if only I can quantum tunnel from #AGBT18 to #TRICON going on simultaneously in SF, NOW YOU ARE TALKING.
9:25pm February 13th 2018 via Hootsuite in reply to chenghlee
Costa: Different discordant results (4/14) were 3 FISH FP, FNs, no result; 1 was Fix-C FN. STAT6: turned out adj genes too close #AGBT18
9:21pm February 13th 2018 via Hootsuite
Costa: 14 different kind of sarcomas and carcinomas; tumor cellularity from 20% to 90%; did FISH on all, and showed 93% concordance. #AGBT18
9:20pm February 13th 2018 via Hootsuite
Costa: Fusion illustrated: striking a density, crisp edges of a SV event. Dovetail has a tool Selva for automated detection #AGBT18
9:19pm February 13th 2018 via Hootsuite
Costa: Chimeric reads mapped back: shows the dots w/chimeric reads, and how close together. Higher-order events - further away #AGBT18
9:18pm February 13th 2018 via Hootsuite
Costa: Crosslink chromatin, digest the ends, biotinylate, ligate ends, remove the crosslinks. Sequence the proximity ligated frag's #AGBT18
9:16pm February 13th 2018 via Hootsuite
Costa: Insert lengths much shorter. Clinical methods used at present: FISH, RT-PCR, DNA/RNA-seq. #AGBT18
9:14pm February 13th 2018 via Hootsuite
Costa: In FFPE challenges: purity, LoD, heterogeneity, FFPE degradation. 'The biggest problem'. Shows insert-size dist of FFPE vs FF #AGBT18
9:13pm February 13th 2018 via Hootsuite
Costa: Why structural variation? Very inpt. ALK/RET/ROS fusions for Rx; diagnostic fusions in bone and soft tissue cancers #AGBT18
9:12pm February 13th 2018 via Hootsuite
Costa: Working with Dovetail genomics; using 'Fix-C' from FFPE cancer samples. Chromosome capture conformation. #AGBT18
9:11pm February 13th 2018 via Hootsuite
Helio Costa (Stanford Univ CA) Structural variation detection by proximity ligation from FFPE tumor tissue #AGBT18
9:09pm February 13th 2018 via Hootsuite
Q: Why non-responders to responders? Rotem: Responders it's hard to get a sample from responders (tumor too small!) #AGBT18
9:08pm February 13th 2018 via Hootsuite
Rotem: Tumor cells have intrinsic ability to resist T-cells; now testing with functional assays to validate findings. #AGBT18
9:06pm February 13th 2018 via Hootsuite
Rotem: Resistance score - 10% of cells are highly resistance; saw after CDK4/6inh shrunk to 2%. Follow-up in ex-vivo mouse models #AGBT18
9:05pm February 13th 2018 via Hootsuite
Rotem: Cancer cells: developed a 'resistance score' based upon gene exp profile. Looked at CDK4/6 inh to sensitize to melanoma #AGBT18
9:03pm February 13th 2018 via Hootsuite
Rotem: Of 8 types - only cancer cells, CD8+ T-cells. Surprised: CD8 Tcells have IFN-g signalling up; decrease of checkpt signalling #AGBT18
8:57pm February 13th 2018 via Hootsuite
Rotem: Fresh tissue, after FACS into immune cells and cancer/stromal cells. (Had to work fast.) 30pts, 10,000 cells, 8 cell types #AGBT18
8:56pm February 13th 2018 via Hootsuite
Rotem: Map mechanisms for resistance, predict responses. Have 30 pts; 15 untreated, 15 non-responders. Cells separated, FACS sort #AGBT18
8:55pm February 13th 2018 via Hootsuite
Rotem: ImmunoRx changed the landscape; yet 65% of melanoma pts do not respond; lack of predictive biomarkers; wide immune evasion #AGBT18
8:54pm February 13th 2018 via Hootsuite
Rotem: The Center for Cancer Precision Medicine is between Dana-Farber, B&W Hospital, and Broad, to address problems like recurrence #AG
8:53pm February 13th 2018 via Hootsuite
