MH: Can screen for KRAS-Effector protein-protein interaction inhibitors. Showed dose-dep effect #AACR15
5:40pm April 21st 2015 via Hootsuite
Matthew Holderfield (NCI Frederick MD) Starts with KRAS mutated cancers into all different alleles - hard to draw conclusions MH #AACR15
5:34pm April 21st 2015 via Hootsuite
RB:Q:Why not CRISPR? A:Possible, not ruled out. But want to knock down many nodes at once. #AACR15
5:31pm April 21st 2015 via Hootsuite
RB: Analysis goal is multi-parameter integrated analysis; 'haven't been able to ask before'. Large # cell lines x Large # of nodes #AACR15
5:29pm April 21st 2015 via Hootsuite
RB: Survival, metabolism, autophagy... look at single cells rather than populations. 'Cell viability' is considered extreme endpoint #AACR15
5:21pm April 21st 2015 via Hootsuite
RB: Know that isoform redundancies; can multiplex to picomolar range; siRNA is hetergeneous. A complex network w/ many param's #AACR15
5:20pm April 21st 2015 via Hootsuite
RB: Goal to correlate biomarkers to biological response after siRNA knockdown. What are critical downstream effectors? #AACR15
5:18pm April 21st 2015 via Hootsuite
Rachel Bagni (NCI Frederick MD) "Validating RAS and its effectors using siRNA (siREN)" #AACR15
5:17pm April 21st 2015 via Hootsuite
FM: Funding opportunities PAR 14-314 due July 8 '15 #AACR15
5:16pm April 21st 2015 via Hootsuite
FM: Biophysical analysis - Andy Stephen. Invites joining to email list, all contact info on the http://t.co/S93s2BvctR website #AACR15
FM: Multimerization & localization assays headed by Tommy Tubyville. Structural biology by Dhirendrea Simanshu 'extremely impt' #AACR15
5:13pm April 21st 2015 via Hootsuite
FM: Identifying surface proteins, headed up by Gordon Whiteley; Computational analysis headed by Bob Stephens, Gad Getz #AACR15
5:12pm April 21st 2015 via Hootsuite
FM: The NCI RAS Initiative homepage http://t.co/5ZPtvOxTP8 Presented a crowd-improved 'Ras 2.0 Pathway' diagram #AACR15
5:10pm April 21st 2015 via Hootsuite
Frank McCormick (UCSF CA) "The NCI RAS Initiative at the Frederick National Laboratory for Cancer Research" FM #AACR15
5:09pm April 21st 2015 via Hootsuite
VV: At Pers. Genome Diagnostics: looking at somatic rearr ass'd with MET amplification #AACR15
2:57pm April 21st 2015 via Hootsuite
VV: Another: '13 ref http://t.co/LXg6ygSlW7 WGS analysis from plasma, picked up variant missed in WES #AACR15
VV: cfDNA can detect recurrence in 3mos, when imaging couldn't pick it up until 9mos. Thus: a window for add'l therapy #AACR15
2:55pm April 21st 2015 via Hootsuite
VV: Looked at pt muts, K-M curve showed dramatic difference, when mutations ID'd in plasma. Data for panc ca. #AACR15
VV: 'Can det. plasma alterations that are not present in tissue'. Minimal resid disease: '08 Nature ref http://t.co/MM1VkOhiXn #AACR15
2:54pm April 21st 2015 via Hootsuite
VV: Onto point muts: many genes (60) and rearr. Sens down to 0.1% in cfDNA. Lung ca: can recreate what's present in tissue #AACR15
2:53pm April 21st 2015 via Hootsuite
VV: Can detect actionable genetic alterations: direct detection of ERBB2 and CDK6 amplifications & rearrangement. #AACR15
2:51pm April 21st 2015 via Hootsuite
VV: 'It's kind of unnerving how much circulating tumor DNA' is in individual. 5y later: same alterations there. Ongoing monitoring #AACR15
2:50pm April 21st 2015 via Hootsuite
VV: The concept of monitoring over course of therapy. Almost to zero - fig from '10 ref http://t.co/9Qc4LrgjX1 CN analyses of cfDNA #AACR15
2:49pm April 21st 2015 via Hootsuite
VV: Recently - '14 STM ref http://t.co/kcQdDXbxZC circulating tumor DNA detects across tumor types; variety of levels, measurable #AACR15
2:47pm April 21st 2015 via Hootsuite
VV: Plasma aneuploidy score; detected re-arrangements (both inter and intra-chrom changes). All cancers to-date found rearr. #AACR15
2:46pm April 21st 2015 via Hootsuite
VV: Challenge for liquid biopsy - so much free DNA. PARE: Leary '12 http://t.co/P3igxQwxTV chart - CNAs from indiv's. #AACR15.
2:44pm April 21st 2015 via Hootsuite
VV: Genes, pathways, and therapeutic interventions. Ex - PIK3CA '04 Science ref http://t.co/YGuWZrgCP9 #AACR15
2:42pm April 21st 2015 via Hootsuite
VV: 'We clearly live from a genomics point of view in an exciting time'. Seq analysis of first 100 cancer genomes chart (v busy!) #AACR15
2:41pm April 21st 2015 via Hootsuite
Victor Velculescu (Johns Hopkins Kimmel MD) “Liquid biopsy approaches for characterizing cancer genomes” VV #AACR15
2:40pm April 21st 2015 via Hootsuite
LD: Genome Variant Invest. Platform (GenomeVIP) Portal here but not live yet: http://t.co/Lp5eitUEj5 http://t.co/6fGKxqeRn0 #AACR15
12:24pm April 21st 2015 via Hootsuite
LD: Ends with slide entitled 'Looking forward to the cloud'. As enables larger studies. '10 Genome Biol ref http://t.co/JahQQ34KDg #AACR15
12:22pm April 21st 2015 via Hootsuite
RT @TCGAupdates: LD: We got a great turnout to analyze data. I call this "International Mutation Calling Festival" #AACR15
12:14pm April 21st 2015 via Hootsuite
LD: For indels 'really not pretty'. SV breakpoints - better than indels, 'still not very good'. Over 50% pipeline dependent. #AACR15
12:13pm April 21st 2015 via Hootsuite
LD: Var counts widely distributed - 10^3 to 10^6 (!) About 10K SNV calls/sample. Barchart of callers; 'picture is not very pretty' #AACR15
12:12pm April 21st 2015 via Hootsuite
LD: Mentions this '14 review http://t.co/RFKoFwjefV Paid attention to library size insert, had 3 prod pipelines, 12 local ones #AACR15
12:10pm April 21st 2015 via Hootsuite
LD: ICGC pilot-63: 63 T/N pairs; 50 will be validated, w/same DNA prep & WGS. Tumor purity est. from 85% down to 30% #AACR15
12:08pm April 21st 2015 via Hootsuite
LD ICGC pan-cancer mut calling 'Pilot 63'; also NCI's turnkey var analysis project. Test alignment, calling, analysis pipelines #AACR15
12:07pm April 21st 2015 via Hootsuite
LD: Mistakes: 5 dimensions. Seq approach; types of var's; diverse datasets; diverse storage locations; diverse data sizes. #AACR15
12:06pm April 21st 2015 via Hootsuite
Li Ding (Washington Univ MO) "Challenges and approaches for mutation discovery and validation in pan-cancer projects" LD #AACR15
12:03pm April 21st 2015 via Hootsuite
IG:Q:Comment on tools used? A:Some used same tool - developer themselves use their own tool the best. Key - high quality pipeline #AACR15
12:02pm April 21st 2015 via Hootsuite
IG: There is a huge need for a training set; the v1.2 set is here and available 2 manuscripts; one here: http://t.co/JFhq7vC9kc #AACR15
12:00pm April 21st 2015 via Hootsuite
IG: Pipelines 'contain many components the performance of which is not clear to the user'; 'hard thresholds do not work' #AACR15
11:58am April 21st 2015 via Hootsuite
IG: Illustrating the 'ideal picture' w/Mona Lisa, 'you choose your mistakes'. Same concl as GG: mut detection not a solved problem #AACR15
11:57am April 21st 2015 via Hootsuite
IG: FP by feature: adjacent to tandem repeats & homopol - non-BWA aligners used by 3 participants. #AACR15
11:56am April 21st 2015 via Hootsuite
IG: Dense plots of FN, TP, FP across 4 participants - much variation between analysis groups #AACR15
11:54am April 21st 2015 via Hootsuite
IG: Manual inspection scored manually for Gold set. One group - good specf. but insensitive. SIMs: 'story quite bad' missing 80% #AACR15
11:52am April 21st 2015 via Hootsuite
IG: Ver 1.2 w/better quality initial data; but still SSM chart looked very similar. SIM: "quite horrible"; 1 agreement across all #AACR15
11:50am April 21st 2015 via Hootsuite
IG: Many plots of %GC against normalized reads, tumor vs. control. From experienced centers - wide variation observed. #AACR15
11:48am April 21st 2015 via Hootsuite
IG: Gold verification set 'due to tech-specific issues'; approach didn't also allow for assessment of FP rate. GIGO paradigm... #AACR15
11:44am April 21st 2015 via Hootsuite
IG: Chart of sensitivity vs. specificity for SSMs some were good; SIMs many were poor. Issue: input data 'not the most fantastic' #AACR15
11:43am April 21st 2015 via Hootsuite
