ER: "This is a meaningless slide but I have to show it" - hairball of SL-interactions between 2,077 genes, 2,816 interactions #AACR15
11:00am April 18th 2015 via Twitter Web Client
ER: Take predictions, match drugs that target SL genes for repurposing. Example: VHL SL-partners ID 6 drugs; each sensitive #AACR15
10:59am April 18th 2015 via Twitter Web Client
ER: 23K genes, 529M x 9 datasets of gene pairs, 4,671M tests. From six publ. screens, est accuracy of 80%. ROC curve shown #AACR15
10:57am April 18th 2015 via Twitter Web Client
ER: Can use shRNA-based functional examination - inactive A, B knockdown and showed to be essential. Also pairwise gene co-exp. #AACR15
10:54am April 18th 2015 via Twitter Web Client
ER: Developed DAISY to choose synthetic lethals from cancer genomes Cancer Cell ref http://t.co/VA92iTnrXW #AACR15
10:52am April 18th 2015 via Twitter Web Client
ER: 2013 Nature Med ref http://t.co/i1WYtiNea5 perspective paper #AACR15
10:50am April 18th 2015 via Twitter Web Client
ER: SL if single inhibition of either gene is not lethal, but inhibition of both is. Harwell 1997 http://t.co/W1HDVwVVrs #AACR15
10:49am April 18th 2015 via Twitter Web Client
Eyton Ruppin (Univ MD) “Predicting cancer-specific vulnerability via data-driven detection of synthetic lethality" ER #AACR15
10:47am April 18th 2015 via Twitter Web Client
DP: Drug cocktails: onc drivers, non-onc dependencies, network nodes, novel & common vulnerabilities, boost immune system #AACR15
10:43am April 18th 2015 via Twitter Web Client
DP: Can get synthetic lethality by inhibiting DDR and increasing hypoxia. May apply to other tumor types. #AACR15
10:40am April 18th 2015 via Twitter Web Client
DP: Cp shBRAF vs. shCHEK1, in vivo response different. Observes loss of DDR kinases in vivo after expansion. #AACR15
10:37am April 18th 2015 via Twitter Web Client
DP:ID of novel druggable targets for combination therapy: run parallel in-vitro and in-vivo shRNA screens #AACR15
10:34am April 18th 2015 via Twitter Web Client
RT @meissner_t: DP: copywriteR https://t.co/2UjMTlikXy off-target reads to improve CNV detection on exome seq #AACR15 no reference needed
10:31am April 18th 2015 via Twitter Web Client
DP:Showing MITF loss ass'd with in/extrinsic BRAF1 resisence; also seen in acquired resistance. AXL induced #AACR15
DP:Also copy-number alterations (CNA); CopywriteR works on either WGS or targeted sets (360 genes), reference-free #AACR15
10:26am April 18th 2015 via Twitter Web Client
DP: Showing pleiotropy in targeted drug resistance; several mutations ubiquitous, others shared, still others unique #AACR15
10:24am April 18th 2015 via Twitter Web Client
DP:Challenge is # of mutations; melanoma in particular from Alexandrov 2013 http://t.co/QG1EL0Fklx 30K mutations #AACR15
10:23am April 18th 2015 via Twitter Web Client
DP: Started with striking photos of individ. from Wagle 2011 paper, pretreatment, much better at 4mos, much worse at 6mos. #AACR15
10:21am April 18th 2015 via Twitter Web Client
Big data session: Daniel Peeper (Netherlands Cancer Inst) “Large-scene perturbations to reveal cancer dependencies” DP #AACR15
10:19am April 18th 2015 via Twitter Web Client
AT: CD47, MET, CD44+ EPCAM 'contain functional and transplantable Metastasis Initiating Cells'. Freq: 1%-44% of CTCs #AACR15
10:02am April 18th 2015 via Twitter Web Client
AT: Summary: CD44, MET, CD47 markers of metastatic stem cells; 12% of all tumor cells in aggressive disease #AACR15
9:58am April 18th 2015 via Twitter Web Client
AT: High-risk individs (>5CTCs/7.5mL) easier to get successful xenografts. #AACR15
9:54am April 18th 2015 via Twitter Web Client
AT: "Phenotype and biology of CTC's are almost a 'black box'" From br ca samples, enumerate, ID EPCAM and show metastatic potential #AACR15
AT: CellSearch has been 'instrumental in the last 20y'. Showed Meier-Kaplan for br ca, EPCAM and survival. http://t.co/ep02bYoYVv #AACR15
9:52am April 18th 2015 via Twitter Web Client
AT: They expect metastasis stem cell from CTCs. Fig from 2012 http://t.co/85AYTLR7N0 Distant met has to have stem-cell-like capacity #AACR15
9:51am April 18th 2015 via Twitter Web Client
AT: This 2014 ref http://t.co/K1EAUSfkoD figure - 'it's clear a combination of genetic and epigenetic factors' for CSCs #AACR15
9:49am April 18th 2015 via Twitter Web Client
AT: Refers to recent Vogelstein correlation between total stem cell divisions in smaller vs larger organs #AACR15
9:46am April 18th 2015 via Twitter Web Client
AT: Niche reprogramming - showed 5 major papers, one NEJM http://t.co/nqqgmmIEFg first mut's in normal HSCs #AACR15
AT: SC self-renewal combines proliferation & inhibition of differentiation. Epigenetic control of 3 fates via niche inhibition #AACR15
9:44am April 18th 2015 via Twitter Web Client
AT: View from 2001: Cancer stem cell figure from ref http://t.co/ra2g6e4JUa In 2015: Genetic and CSC hetergeneity (epistatic) #AACR15
9:43am April 18th 2015 via Twitter Web Client
AT: Adult tissue stem cells 'essential to maintain and repair regenrative tissues' Billion/day, 100g/week. #AACR15
9:41am April 18th 2015 via Twitter Web Client
Andreas Trumpp (German Cancer Ctr Heidelburg) "Malignant stem cells in the circulation" AT #AACR15
9:40am April 18th 2015 via Twitter Web Client
CD: Q about CTC's and COPD: "Evidence that CTC's leave the mother ship early in carcinogenesis" #AACR15
CD: Concludes with an individual with aggressive SCLC and its characterization. #AACR15
9:38am April 18th 2015 via Twitter Web Client
CD: Referred to this 2014 BMC Genomics http://t.co/jpx6GEowSV doing single-cell RNA-Seq Also data from scWES #AACR15
9:34am April 18th 2015 via Twitter Web Client
CD: PCA plot of CNV data from 6414 protein-coding genes from 3 individs - responsive, & 2 refractory; some trends observed #AACR15
9:33am April 18th 2015 via Twitter Web Client
CD: Cell-by-cell heterogeneity - 'we need to do more of this to understand it more fully'. #AACR15
9:31am April 18th 2015 via Twitter Web Client
CD: Can do single-cell sequencing; shows spec TP53 mutation in bulk. Laid out bioinformatic workflow; WBCs -ve control #AACR15
9:30am April 18th 2015 via Twitter Web Client
CD: DEPArray instrument is 'a big American fridge' (large); explains dilectric cages. Blog on BtB: http://t.co/7rkGgtS9tY #AACR15
CD: Their workflow - 'analyze w/in 4d' w/CellSearch or Parasortix. Biobank in glycerol. Can do cfDNA. CTC isol. w/DEPArray. #AACR15
9:28am April 18th 2015 via Twitter Web Client
CD: Looking at CDX models from individual samples, can look at copy-number: clear pattern of gain/loss between sensitive / non-sens #AACR15
9:26am April 18th 2015 via Twitter Web Client
CD: Showed difference between chemo-sens and chemo-refractory. Get CTC-Derived Explants (called CDX) in-vitro model #AACR15
9:25am April 18th 2015 via Twitter Web Client
CD: Can bank CTCs in glycerol - 'an important step for us' b/c of real time nature. 2014 Nature Med http://t.co/vK8DoRglVr #AACR15
9:23am April 18th 2015 via Twitter Web Client
CD: CellSearch - showed data from this 2012 JCO paper http://t.co/3qwailpeG6 #AACR15
9:21am April 18th 2015 via Twitter Web Client
CD: SCLC (20% of all lung ca): CTC research 'has a real role to play' since the biology is poorly understood, small tissue amounts #AACR15
9:19am April 18th 2015 via Twitter Web Client
CD: 'CTC research is not for the faint hearted'. Not plug-and-play. #AACR15
9:17am April 18th 2015 via Twitter Web Client
CD: Turnaround time? Real time analysis or bank? Cost? Bioinformatics? What to measure (DNA, RNA, protein)? #AACR15
CD: Which to choose? "It depends on what you want'. Is it marker-dependent? Sample coll? QC? Fixed? Single or pools of cells? #AACR15
9:16am April 18th 2015 via Twitter Web Client
CD: Vitatex is a functional selection (for invasiveness). Gilupi nano detector - looking for EpCAM. They use DEP Array & ImageStream #AA
9:15am April 18th 2015 via Twitter Web Client
CD: DEPArray, ImageStream for imaging. 'Marker-dep and indep approaches, larger blood volumes' #AACR15
9:14am April 18th 2015 via Twitter Web Client
