Spira: #AACR18 Quotes Volgelstein '17 in ASCO Post "Cardiologists are doing it right - the focus has been on prevention' of massive infarcts
1:19pm April 18th 2018 via Hootsuite
Avrum Spira (Boston Univ MA) Prevention and Survivorship/Precision Prevention and Interception #AACR18
1:18pm April 18th 2018 via Hootsuite
Mardis: Layout is four talks: Prevention (Spira), Basic Research (Mardis), Clinical, and Look to the Future talks. #AACR18
1:17pm April 18th 2018 via Hootsuite
Elaine Mardis giving the closing introduction at #AACR18 https://t.co/WZU3pi33Y2
Shah: #AACR18 Can now do CNV analysis on thousands of cells. Shows graph of increase from 4/17 to now: 167k cells, 216 libraries
12:34pm April 18th 2018 via Hootsuite
Shah: #AACR18 Have worked on opening up from microfluidic platform (cumbersome) to robotic pin nano-well, 5K-well arrays, can pool and seq
12:33pm April 18th 2018 via Hootsuite
Shah: #AACR18 Can bin reads across intervals, to get CNV inferred from low-coverage sc genomes. Can pool and get higher resolution (SNVs)
12:32pm April 18th 2018 via Hootsuite
Shah: #AACR18 Interested in rare poplns, want statistical power. Tagmentation - '17 https://t.co/NeOHTPt3Ub but only get sparse represent.
12:31pm April 18th 2018 via Hootsuite
Shah: #AACR18 sc measurements at scale:decomposing cancer into its constituent parts; errors are present. Thus scWGS and phase and haplotype
12:30pm April 18th 2018 via Hootsuite
Shah: #AACR18 Points out individual clones from original tumor, led to brain met, and secondary recurr. Visual '17 https://t.co/GgPgTzple7
12:29pm April 18th 2018 via Hootsuite
Shah: #AACR18 Modeling: an ov ca cell map (metastatic to brain) and secondary relapse and sequenced clones '16 ref https://t.co/j362nPV2sY
12:28pm April 18th 2018 via Hootsuite
Shah: #AACR18 What cell popln's constitute a tumor? Can trajectories be predicted? What is their behavior?
12:26pm April 18th 2018 via Hootsuite
Shah: #AACR18 Now onto the genome of malignant cells; WGS and working with Sam Aparicio at BCCA. Cancer as dynamic raises Q's.
12:25pm April 18th 2018 via Hootsuite
Sohrab Shah (BC Cancer Agency CA) Scalable single cell whole genome sequencing: Towards population genetics of cancer #AACR18
12:24pm April 18th 2018 via Hootsuite
Q: Any way to do spatial hi-dimensional methods? Shields: Will lose info w/dissociation of cells. Will go that way #AACR18
Q: Always see 3 populations? Shields: Likely at day 11; looking at other cancer types as well #AACR18
12:22pm April 18th 2018 via Hootsuite
Q: Spatial imptc? Shields: Likely, what these cells are producing in local environment, if populations affect each other #AACR18
12:20pm April 18th 2018 via Hootsuite
Shields: #AACR18 Id'd 'inflammatory CAFs' - CXCL12-expressing CAFs that recruit macrophages.
12:19pm April 18th 2018 via Hootsuite
Shields: #AACR18 Shows progression of CD8 T-cell expansion from naive, to active, to exhausted over time. 309 CAFs over time points: 3 clust
12:13pm April 18th 2018 via Hootsuite
Shields: #AACR18 Remove tumor cells (mCherry+), narrow immune populations. Shows immune cell subpopulations; also by site, and over time
12:10pm April 18th 2018 via Hootsuite
Shields: #AACR18 Thus scRNASeq; explore CAF heterogeneity in tumor microenv. Subcut inj of B16 melanoma, 3 time points
12:09pm April 18th 2018 via Hootsuite
Shields: #AACR18 Feig et al and Ozdemier et al had different results. Depleting CAFs decr / incr tumor growth? https://t.co/uUV9XKWeRV
12:08pm April 18th 2018 via Hootsuite
Shields: #AACR18 Not universal CAF marker (carcinoma assoc'd fibroblast). They are hetergeneous population of cells. What roles?
12:07pm April 18th 2018 via Hootsuite
Shields: #AACR18 Lymphatic biology: podoplanin in tumor stroma related to poor prognosis. Immune cell direct interact. Fibroblast role?
12:06pm April 18th 2018 via Hootsuite
Shields: #AACR18 Growth factors, angiogenesis, lymphangiogenesis, invasion and metastasis, ECM remodeling. Recent: immune infiltration
12:03pm April 18th 2018 via Hootsuite
Shields: The tumor microenv - blood vessels, lymph vessels, macrophages, fibroblasts, neutrophils, lymphocyte, extracell matrix #AACR18
12:02pm April 18th 2018 via Hootsuite
Jacqui Shields (Univ Cambridge UK) Exploiting single cell approaches to define the evolving tumor microenvironment #AACR18 (All unpubl work)
12:01pm April 18th 2018 via Hootsuite
Shain: #AACR18 Shows p14 not indicative for invasion. Zheng Judson Cancer Cell (in revision), bi-allelic los of CDKN2A init mel invasion
11:54am April 18th 2018 via Hootsuite
Shain: #AACR18 Cell cycle disruption too: CDKN2A encodes p16/INK4A and p14/ARF, produce two products. Shows p16 low-level w/invasive
11:53am April 18th 2018 via Hootsuite
Shain: #AACR18 Shows clear expr. clustering data, between nevus and invasive. A shift forward to polycomb repressive complex 2.
11:51am April 18th 2018 via Hootsuite
Shain: #AACR18 SWI/SNF and PRC2 are antagonistic; reviews benign vs malignant polycomb targets, H3K27me3 blocked in benign.
11:50am April 18th 2018 via Hootsuite
Shain: #AACR18 TERT promoter mut status correlated w/progression stage. Now onto Chromatin remodeling gnees (ARID2, 1A,1B, SMARCA4, PBRM1)
11:49am April 18th 2018 via Hootsuite
Shain: #AACR18 Melanomas and MAP-Kinase gene exp signature - early during progression, subsequent ampl. Up-reg of telomerase TERT next
11:48am April 18th 2018 via Hootsuite
Shain: #AACR18 From 82 cases, 430 areas. 2 publ: https://t.co/dcO2iH2yBM and one new one in Cancer Cell. MAPK-mut alleles: high levels in mM
11:47am April 18th 2018 via Hootsuite
Shain: #AACR18 By the time invasive melanoma detected, it has spread already. ID'd 82 cases w/remnant precursor lesions. Microdissected.
11:44am April 18th 2018 via Hootsuite
Shain: Melanoma starts on one side w/melanocytic nevi (mole), then lesioins, T1-T4 then metastatic melanoma (mM). Idea:full spectrum #AACR18
11:43am April 18th 2018 via Hootsuite
Hunter Shain (UCSF CA) Genomic, transcriptomic analysis reveals incremental disrupt. of key signaling pathways during melanoma evol #AACR18
11:42am April 18th 2018 via Hootsuite
A2: Landau #AACR18 500K CpGs with modest 1M reads. More seq doesn't provide much more. About 10% overlap between cells as epimut rate high
11:41am April 18th 2018 via Hootsuite
Q: Sparsity, missing data? Landau: Treat as an ally. RRBS limits target to 5M CpGs. Thus sparse info still gives chance to reconstr. #AACR18
11:40am April 18th 2018 via Hootsuite
Q: Does sc data capitulate CLL bulk? Landau: In unmut CLL, epimut is lower; later mut forms (B-cells) branch lengths are longer #AACR18
11:34am April 18th 2018 via Hootsuite
Landau: concl: CLL epimutation rate uniformly elevated; serves as molecular clock; epiphylogen. tree - native lineage tracing system #AACR18
11:32am April 18th 2018 via Hootsuite
Landau:Can ask question about transcriptional similarity, and clade-spec signatures; volcano plot shows two spec subpopulations #AACR18
11:31am April 18th 2018 via Hootsuite
Landau: T2-enriched clade in ibrutinib-sensitive cells in CLL from lymph node; points out high resolution of technique #AACR18
Daniel Landau (Weill-Cornell NY) Single-cell epigenomics reveal the epigenetic evolution and lineage histories of c… https://t.co/nIYt1Z6AAJ
Prasad: #AACR18 "I disagree with use of FD1CDx and off-label Nof1 studies with NO RECORD KEEPING, NO REPORTING..."… https://t.co/U2oQpPBC15
6:50pm April 17th 2018 via Hootsuite
Prasad: #AACR18 From NYT piece, "...I have a hunch that..." There are true successes here but few, and growing only at a linear rate
6:49pm April 17th 2018 via Hootsuite
Prasad: #AACR18 The year that MDA put a slide up there, they published Bernstam JCO 2015 only 6% enrolled. (Now up to 25%)
6:48pm April 17th 2018 via Hootsuite
Prasad: #AACR18 Could be clonal heterogeneity. Giving Rx with only a subset of cancer clones? Anectdotes: from article in-press...
6:42pm April 17th 2018 via Hootsuite
Prasad: #AACR18 'But one is tissue, one is blood'. Even when both tissue: F1CDx, PCDx (Weiss GJ) 9 pts 9 drugs overlap, F1CDx vs G360
6:41pm April 17th 2018 via Hootsuite
Prasad: #AACR18 Problems with test: In 56 pts, get 133 muts sent back. Guardant360: 120 muts sent back. Only 36 overlap.
6:40pm April 17th 2018 via Hootsuite