Strong: Looking at ctDNA - Bettegowda Sci Trans Med 2014 paper PubMed http://t.co/SZMRhqmo9R 'could be nice proof of principle' #AACR14

4:27pm April 5th 2014 via Hootsuite

Strong: Showed varying results across 12 WGS samples reported in Dewey et al JAMA PubMed http://t.co/97DymBl42w #AACR14

4:25pm April 5th 2014 via Hootsuite

Strong: Lack of consensus, lack of std'ized processes with NGS (laundry list incl. pipelines, curation, phenotype/genotype DBs #AACR14

4:22pm April 5th 2014 via Hootsuite

Strong: Other barriers are primary care provider attitudes, education Strong et al 2014 PubMed http://t.co/3NWVvOHxog #AACR14

4:19pm April 5th 2014 via Hootsuite

Up first: session chair Louise Strong, UT MD Anderson Barriers to NGS in the clinical research setting - public attitudes #AACR14

4:16pm April 5th 2014 via Hootsuite

Educational session: "Clinical Cancer Genetics in the Next Generation Sequencing Era" #AACR14

4:14pm April 5th 2014 via Hootsuite

Zender: Upon knockdown, decrease in Raf1, MEK, Erk indicating cross-signalling #AACR14

2:35pm April 5th 2014 via Hootsuite

Zender: p38 MAPK signalling: suppression plus sorafenib, used @ingenuity IPA with gene expression for analysis #AACR14

2:34pm April 5th 2014 via Hootsuite

Zender: Used 250 shRNAs of 100 human HCC's with focal genome amplifications #AACR14

2:28pm April 5th 2014 via Hootsuite

Zender: Use mouse liver cancer mouse model and stable RNAi to directly conduct in-vivo work on Sorafenib sensitizers #AACR14

2:27pm April 5th 2014 via Hootsuite

.@mucociliary Thank you for the kind words, Ian.

2:20pm April 5th 2014 via Hootsuite in reply to

Zender: Mouse model for hepatocellular carcinoma. Tn vector, a few weeks to (end-point) #AACR14

2:18pm April 5th 2014 via Hootsuite

Zender: >90% of all oncology Phase I trials fail; 'the pre-cliinical bar should be higher' #AACR14

2:16pm April 5th 2014 via Hootsuite

Next up: Lars Zender Univ Hosp Tuebingen "In vivo functional genetic screens" #AACR14

2:13pm April 5th 2014 via Hootsuite

Root: Q:P53 and MDM4 dependency? A: Have seen non-intuitive direction, inverse directions than expected #AACR14

2:12pm April 5th 2014 via Hootsuite

Root: A: CRISPR can also have other off-target effects, yet to be fully known. Also: what fx has the knockout? +/- selelection... #AACR14

2:10pm April 5th 2014 via Hootsuite

Root: Q:CRISPR vs RNAi in med term? A: Haploinsufficiency different than knockout; anectdotally - different effects (CYCLOPS) #AACR14

2:09pm April 5th 2014 via Hootsuite

Root: Also other tools include mouse in vivo xenografts, growth in agar, co-cultured cells #AACR14

2:07pm April 5th 2014 via Hootsuite

Root: Can use other tools - CRISPR, used for both + and - selection screens, they are doing that but in progress how well it works #AACR14

2:06pm April 5th 2014 via Hootsuite

Root: Achilles is available - find genes that have shown dependencies per shRNA screen http://t.co/YfRI4SVN36 #AACR14

2:04pm April 5th 2014 via Hootsuite

Root: This 'CYCLOPS' work described here in 2012 Cell (PubMed) http://t.co/9buNt1lV1J #AACR14

2:03pm April 5th 2014 via Hootsuite

Root: Dependency ass'd with copy number loss: CYCLOPS: a subset of hemizygously deleted genes that are highly essential #AACR14

2:02pm April 5th 2014 via Hootsuite

Root: Looked at Wnt active vs non-active across 102 cell lines. "Genes to pathways to networks"; codependency examples #AACR14

2:01pm April 5th 2014 via Hootsuite

Root: Looked at ARID1B as essential for ARID1A mutant tumor cells Refers to Helming PubMed ttp://ow.ly/vsZ6L #AACR14 h

1:58pm April 5th 2014 via Hootsuite

Root: PIK3CA mut's, many others - found 9 known and 5 new discoveries, Q-values <10^5, using Achillles 2.4 #AACR14

1:57pm April 5th 2014 via Hootsuite

.@zmadak Have to think pretty fast too - esp when looking up stuff on the web. Love the 'Wang et al PLoS One 2012' reference. 2400 found!

1:56pm April 5th 2014 via Hootsuite in reply to

.@zmadak No, just Firefox on an old XP machine, use Hootsuite (could use Twitter's main interface, just preference). And I type pretty fast.

1:55pm April 5th 2014 via Hootsuite in reply to

Root: Ceveloped a gene scoring method. Citation: Tsherniak Ataris tool PubMed http://t.co/eqymzpjILY #AACR14

1:53pm April 5th 2014 via Hootsuite

Root: Use about 5 shRNA's/gene, effects vary in terms of off-target, varying suppression level. Can't just average out signal #AACR14

1:52pm April 5th 2014 via Hootsuite

Root: But also found idiosyncratic genes in their cell lines as well. #AACR14

1:51pm April 5th 2014 via Hootsuite

Root: In 12 lines also ID's cell-line-specific essential genes. BCR / ABL in K562 line (CML leukemia line) #AACR14

1:51pm April 5th 2014 via Hootsuite

Root: Project Achillles - how the pooling shRNA libraries is impt; http://t.co/riKQ0qL5Lt ID'd 8 commonly essential genes (12 lines) #AACR14

1:50pm April 5th 2014 via Hootsuite

Root: Cancer Cell Line Encyclopedia resource at the Broad Inst here: http://t.co/vySZqIPqyv #AACR14

1:48pm April 5th 2014 via Hootsuite

Root: Approach - large # of ca cell lines, activation of pathways, link dependencies and genetic features; then assess these #AACR14

1:47pm April 5th 2014 via Hootsuite

Next up: David Root Broad Inst "Large-scale screens for cancer cell genetic dependencies " #AACR14

1:43pm April 5th 2014 via Hootsuite

Barnards: Q: Combination of genes? A: Biology too complex to address to target multiple genes in a functional model. #AACR14

1:41pm April 5th 2014 via Hootsuite

Bernards: Genome analysis is fine (alterations of pathways), but need functional genetic analysis with cross-talk between pathways #AACR14

1:39pm April 5th 2014 via Hootsuite

Bernards: They have four ongoing combination experiments based upon synthetic lethality screens #AACR14

1:37pm April 5th 2014 via Hootsuite

Bernards: Looked at negatively selected haripins, 580 kinases, 3 significant ones that had different hairpins target same gene #AACR14

1:35pm April 5th 2014 via Hootsuite

Bernards: What is resp. for BRAF inhibitors in colon cancer? BRAF V600E mutants; which kinase synergizes with PLX? Used shRNA kinome #AACR14

1:33pm April 5th 2014 via Hootsuite

Bernards: FACS-assisted shRNA genetic screen for EGFR expression + vemurafenib resistance; SOX10 knowckdown publ. last week #AACR14

1:29pm April 5th 2014 via Hootsuite

First up: Rene Bernards Netherlands Cancer Inst "Functional genetic screens and their use in cancer research" #AACR14

1:28pm April 5th 2014 via Hootsuite

Next Session: "Functional Cancer Genomics" #AACR14

1:27pm April 5th 2014 via Hootsuite

Khurana: Gerstein's lab tool called FunSeq here: http://t.co/KyJjzXy4OY #AACR14

1:09pm April 5th 2014 via Hootsuite

Khurana: Somatic mut's do not follow same patterns of polymorphism selection; ID'd candidate drivers #AACR14

1:09pm April 5th 2014 via Hootsuite

Khurana: Referring to her work published in Khurana Science 2013 PubMed: http://t.co/KukgQ4JyJQ non-coding regions w/ fn impact #AACR14

1:06pm April 5th 2014 via Hootsuite

Khurana: Looking at germline regions of importance, and cancer mut's then in these regions are driver mutation events #AACR14

1:05pm April 5th 2014 via Hootsuite

Khurana: (Oops, she's looking at SNPs and negative selection, not ncRNAs) #AACR14

1:04pm April 5th 2014 via Hootsuite

Khurana: Dev. method for looking at driver ncRNA: conserved ncRNA regions, enriched for rare var's, depleted common var's #AACR14

1:03pm April 5th 2014 via Hootsuite

Khurana: miRNA and lncRNA mechanisms; HOTAIR and PTEN expression reduction #AACR14

1:02pm April 5th 2014 via Hootsuite