SP: Two years since ACMG incidental findings, focused on non-cancer. '13 ref http://t.co/ODovNUVsBd No medical oncologists on panel #AACR15
7:22am April 22nd 2015 via Hootsuite
SP: The lab & clinician have to communicate; what else is going on. Report on cancer or other pt phenotype, other med actionable #AACR15
7:20am April 22nd 2015 via Hootsuite
SP: Slide from '14 ref http://t.co/LuVlboNWuw Tumor report / Germline report. What other illnesses in family; insure communication #AACR15
7:19am April 22nd 2015 via Hootsuite
SP:(PGx = pharmacogenetic). Risk alleles may not even be on the exome; have to be designed into the platform #AACR15
7:18am April 22nd 2015 via Hootsuite
SP: Germline potential parts: deleterious muts in disease genes related to ca suscept. VUS. Common risk alleles (GWAS). PGx alleles #AACR15
7:17am April 22nd 2015 via Hootsuite
SP:Critical reporting issues for somatic: lower bound for AF? (They use 5%) RNA-Seq? #AACR1
7:15am April 22nd 2015 via Hootsuite
SP: For somatic: nothing comparable to ACMG variant reporting; Mon session had three present 'and all were different' reports. #AACR15
7:14am April 22nd 2015 via Hootsuite
SP: Oncologists do the final signout for somatic muts; geneticists for germline. #AACR15
7:12am April 22nd 2015 via Hootsuite
SP: Matched T/N; use VCRome 2.1 exome-capture; no agreed-upon ratio for seq. They do 1:1; >95% coverage for calling #AACR15
SP: Some clinical trials req tissue for entry; encountered early on, will do a review to insure the last sample isn't used up #AACR15
7:10am April 22nd 2015 via Hootsuite
SP: Working w/surgery & path; getting the normal 'can be a pain' 'not trivial'; decide if entire lab is CLIA or just the final LDT #AACR
7:08am April 22nd 2015 via Hootsuite
SP: Points to this '14 review http://t.co/acjGO0aNoY Compares exomes betw. Adults vs Pediatric. Cp also germline vs tumor workflow #AACR15
7:07am April 22nd 2015 via Hootsuite
SP: At Baylor - two overlapping teams; germline and cancer exome teams listed (Gibbs, Eng, Yang & Muzny; Parsons, Roy, Wheeler & Li)
7:04am April 22nd 2015 via Hootsuite
SP: First (all caps) "Be brave: patients, parents and families want germline results!" Not every family or subject; vast majority do #AACR15
7:03am April 22nd 2015 via Hootsuite
SP: These are smaller studies where there is much closer contact to participants in these clinical trials. #AACR15
7:02am April 22nd 2015 via Hootsuite
Sharon Plon (Baylor College of Medicine TX) Reporting Germline Findings from Clinical Genome Sequencing Trials #AACR15
6:59am April 22nd 2015 via Hootsuite
(Here at #AACR15 it's great to see @splon go around and greet attendees at the 7am 'meet the expert' session on cancer genetics)
New post: Highlights from #AACR15 | http://t.co/bwF4p3qfdb
6:22am April 22nd 2015 via Wordpress Yuzuki Tweet posts
RT @wjsullivan: "Excess of dietary supplements linked to increase cancer risk" http://t.co/bN9gpGNdJd
5:05am April 22nd 2015 via Hootsuite
RT @PathoDiagnostic: #AACR15 news: Vitamin & mineral dietary supplements shown to increase #cancer risk http://t.co/Ynzp5Ozkzq
4:11am April 22nd 2015 via Hootsuite
RT @pickover: Play fractal Tic Tac Toe. Feed your brain. More info: http://t.co/t3t36svR4V http://t.co/8Rlsc5rW1a
4:10am April 22nd 2015 via Hootsuite
Known as a 'high-quality problem' RT @nprscience: Why Handsome Men May Be At A Disadvantage When It Comes To Hiring http://t.co/tuFGYeoUbu
10:45pm April 21st 2015 via Hootsuite
Working 70 hours/week is the same output at 56 hours – Quartz http://t.co/vYYUywNq2X
10:05pm April 21st 2015 via Hootsuite
What it must have been like in 1888? RT @MaxCRoser: The Great Vanishing of Facial Hair (1842-1972) http://t.co/c2cJ5jH4sQ
9:15pm April 21st 2015 via Hootsuite
RT @hardsci: A. Between 1 and 5. Q. How many Bayesians does it take to change a light bulb? A. Between 2 and 5.
8:20pm April 21st 2015 via Hootsuite in reply to hardsci
MT @TheEconomist: As Argentines' highest bill is $11, the gov't is in denial over inflation http://t.co/jF9hj7tFdq http://t.co/fY8R7xsJNd
7:00pm April 21st 2015 via Hootsuite
23-acre Driverless Car Test City in Michigan - BusinessWeek http://t.co/0byehvjFXA
6:30pm April 21st 2015 via Hootsuite
LM:Structural characterization may guide linker synthesis with electrophilicity. #AACR15
6:24pm April 21st 2015 via Hootsuite
LM: Showed LC/MS data, failed to label K-Ras(G12D) with first two compounds. 'I'm showing negative data, please be patient' #AACR15
6:22pm April 21st 2015 via Hootsuite
LM: Others warheads are acylations. Have screened electrophilic analogs of high-affinity S-IIP ligands. Chemistry diagrammed. #AACR15
6:20pm April 21st 2015 via Hootsuite
LM: Types of reactive groups called 'warheads' - alpha-halo carbonyl, sulfonate esters; epoxide (alkylations). #AACR15
6:19pm April 21st 2015 via Hootsuite
JM: Switch-II pocket (S-IIP) novel K-Ras binding site; Ostrem '14. Chose to prioritize Asp - common '12 ref http://t.co/hg3AG4L2fT #AACR15
6:18pm April 21st 2015 via Hootsuite
LM: '10 Ref figure http://t.co/QuYlhA9HIF First direct inhibitors - bind to Ras irreversibly #AACR15 '14 Nature http://t.co/PouwR71EL5
6:16pm April 21st 2015 via Hootsuite
LM: 30y of effort in targeting RAS, very difficult to target. Kinases have 2 uM for ATP; K-Ras has 17pM for GTP. #AACR15
6:13pm April 21st 2015 via Hootsuite
LM:GDP to GTP state: switch 1/2 domains, common mutated positions is 12/13 and 61 closely positioned together. #AACR15
6:12pm April 21st 2015 via Hootsuite
Lynn McGregor (UCSF CA) "Development of an oncogene-specific inhibitor of K-Ras G12D" LM #AACR15
6:11pm April 21st 2015 via Hootsuite
JH: G13D understanding rapid nucleotide exchange for mutant: electrostatic potential map shows strong neg repulsive charge #AACR15
6:02pm April 21st 2015 via Hootsuite
JH: Lack of high-quality crystal structure of mutant KRAS - now have G12C, G12R, G12V, G13D, Q61L (1.04A-1.99A resolution) #AACR15
6:01pm April 21st 2015 via Hootsuite
JH: Analog Mant-GDP/GTP kinetics are all similar, except for G13D - 13x higher #AACR15
6:00pm April 21st 2015 via Hootsuite
JH: Q61H slow hydrolysis; G12C close to WT. Intrinsic GTP hydrolysis rate may be relevant in signaling #AACR15
5:59pm April 21st 2015 via Hootsuite
JH: Looking at GAP-stim GTP hydrolysis assay; 384-well format, PNP enzyme creates A360-absorbance to measure #AACR15
5:58pm April 21st 2015 via Hootsuite
JH: G13D respond well to EGFR inh; none of the others do. So biochemical profiling. #AACR15
5:57pm April 21st 2015 via Hootsuite
JH: TCGA data show high heterogeneity of mutations. Panc, colon, lung: high frequency. Panc - G12D, G12R, G12V. #AACR15
5:56pm April 21st 2015 via Hootsuite
JH: Starts w/diagram: plasma-membrane GTP-ase. Grb2, SOS recruited, once GTP bound, many downstream effectors. Cell cycle, xcrption..#AACR15
5:54pm April 21st 2015 via Hootsuite
John Hunter (UTSW TX) "Biochemical profiling of cancer-associated KRAS mutants" JH #AACR15
5:52pm April 21st 2015 via Hootsuite
MH: Have high content membrane localization assay. Seeking collaborations for compounds to profile. #AACR15
5:50pm April 21st 2015 via Hootsuite
MH: Each line has single lentiviral integration; similar resp to EGF stimulation. #AACR15
5:48pm April 21st 2015 via Hootsuite
MH: Have mouse embryonic fibroblasts (MEFs) absent RAS '10 ref http://t.co/s44bSR2ujk Developed a panel of RAS-dependent MEFs #AACR15
5:47pm April 21st 2015 via Hootsuite
MH:Able to produce nanodisc-KRAS-RBD complex; EM shows w/ and w/o KRAS. #AACR15
5:44pm April 21st 2015 via Hootsuite
MH:But want 'properly processed KRAS'; farnesylated/methylated. Prod in baculovirus; IMAC capture, can get >95% processed KRAS #AACR15
5:42pm April 21st 2015 via Hootsuite
