Marylin Li (CHOP PA): Standards and guidelines for the interpretation and reporting of sequence variants in cancer #AMP2016
7:23am November 12th 2016 via Twitter Web Client
Jennings: Clarify limitations in report. Manuscript reviews were favorable, concepts and rec's should serve as practical resource #AMP2016
7:22am November 12th 2016 via Twitter Web Client
Jennings: E.g. FLT3-ITD - you won't get 59 samples. Options to get orthogonal method until you get 59 w/NGS; or add control. #AMP2016
7:21am November 12th 2016 via Twitter Web Client
Jennings: Error-based approach, perf of similar variants will not be performing differently. Abbrev method validations poss #AMP2016
7:20am November 12th 2016 via Twitter Web Client
Jennings: Can be thru test design, method validation, or quality controls. Not novel, CLSI EP-23 and IQCP #AMP2016
7:19am November 12th 2016 via Twitter Web Client
Jennings: Assess possible sources of error at each step; provide documented evidence error would not occur, or detected #AMP2016
7:18am November 12th 2016 via Twitter Web Client
Jennings: Detecting BRAF V600E, need to detect 59 samples in a row correctly. What about other mutations and mut types? #AMP2016
Jennings: Shows table of 95% reliability, and confidence of 95%, n=58.4. NGS requires 'an error-based or method-based' #AMP2016
7:17am November 12th 2016 via Twitter Web Client
Jennings: 59 samples and assessing coverage - ave coverage is 98%; 95% CI is 97.9%-98.1%; lowest value is 97.1% #AMP2016
7:16am November 12th 2016 via Twitter Web Client
Jennings: The probabily that 1 sample >92% is 95% in a graph. For 59 samples: (0.95)^59 #AMP2016
7:15am November 12th 2016 via Twitter Web Client
Jennings: Tolerance interval if distribution is normal. For non-normal distribution, due to limits at 0% and 100% #AMP2016
7:14am November 12th 2016 via Twitter Web Client
Jennings: Tolerance interval - where 95% of samples will fall (the population distribution), a broader range. 'The next patient' #AMP2016
7:13am November 12th 2016 via Twitter Web Client
Jennings: Sample mean will equal population mean; even with 20 samples, can get 95% CI range can be calculated. #AMP2016
7:12am November 12th 2016 via Twitter Web Client
Jennings: Shows binomial distribution of read depth (if perfect), and what 20 sample points look like along that distribution #AMP2016
7:11am November 12th 2016 via Twitter Web Client
Jennings: Palmetto - 2; CAP - at least 20; NYSDOH - 50 pt samples for validation. Others - not specified. #AMP2016
7:10am November 12th 2016 via Twitter Web Client
Jennings: Manuscript written and submitted to JMD, so this is still draft. 'Current samples for NGS Validation' quiz... #AMP2016
7:09am November 12th 2016 via Twitter Web Client
Lawrence Jennings (Univ Chicago IL) Standards guidelines for development, optimization, and validation of NGS-based oncology panels #AMP2016
Q: Best test for 1p/19q co-del? Aldape: FISH-based assay. If only 1 deleted: either both or none, via unbalanced transloc #AMP2016
1:37pm November 11th 2016 via Twitter Web Client
Q: Role for MGMT methylation status? Aldape: Routine predictive marker for chemo in GBM, impt for wt IDH #AMP2016
1:36pm November 11th 2016 via Twitter Web Client
Aldape: Retrospective cohort 558 lower-grade diffuse glioma (WHO II-III): 85 were IDH wt, shows clear diff by grade via K-M curve #AMP2016
1:31pm November 11th 2016 via Twitter Web Client
Aldape:IDH status and 1p/19q are now used to classify WHO diffuse astrocytic tumors, and oligodendroglial tumors #AMP2016
1:28pm November 11th 2016 via Twitter Web Client
Aldape: Has able to dev a classifier using methylation status, and applied it for GBM. Able to get WHO 'blue book' changed #AMP2016
1:26pm November 11th 2016 via Twitter Web Client
Aldape: Methylation status is stable in tumors; can use ILMN Methyl array, showed data across 50 types of brain tumors #AMP2016
1:22pm November 11th 2016 via Twitter Web Client
Aldape: Shows K-M curves where molecular characterization of IDH wild-type into two sub-groups #AMP2016
1:21pm November 11th 2016 via Twitter Web Client
Aldape: Integrated analysis of CNV, methylation, RNA, microRNA, 2nd-order clustering #AMP2016
1:15pm November 11th 2016 via Twitter Web Client
Aldape: #AMP2016 '15 NEJM https://t.co/R3tgqg98kR via #TCGA further refined model of Diffuse Grade II/III
1:12pm November 11th 2016 via Twitter Web Client
Aldape: IDH1 and change in methylation '12 ref https://t.co/GLD5uJ3MLU Old model '06: 1p/19q co-deletion vs TP53 mut; now IDH, CIMP #AMP2016
1:10pm November 11th 2016 via Twitter Web Client
Aldape: Starts with its GBM's vague classification, and fortunate discovery by Parsons '08 https://t.co/rr8HZY1FnL and IDH #AMP2016
1:08pm November 11th 2016 via Twitter Web Client
Kenneth Aldape (Univ Health Network Toronto CN) Molecular Classification of Glioblastoma and the Implementation for Therapy #AMP2016
1:06pm November 11th 2016 via Twitter Web Client
LiPuma: Diversity increases, as disease progresses diversity declines, explaining overlap of microbial communities #AMP2016
9:34am November 11th 2016 via Twitter Web Client
LiPuma: #AMP2016 '16 ref https://t.co/E1sZOVumje shows a sig underrepresentation of spp. by traditional culture methods
9:30am November 11th 2016 via Twitter Web Client
LiPuma: #AMP2016 '12 PNAS https://t.co/0L6IYQXtvA shows diversity over 8.6y in CF
9:28am November 11th 2016 via Twitter Web Client
LiPuma: Culture-indep profiling by 16S described in '03 https://t.co/TISSY8qBn9 now by NGS. Defines diversity, other terms #AMP2016
9:26am November 11th 2016 via Twitter Web Client
LiPuma: '91 review reflected thinking, P. aeruginosa on top of epithelial cell complex https://t.co/0ZazxC8YwG 30y of work #AMP2016
9:23am November 11th 2016 via Twitter Web Client
LiPuma: Outlines conventional approach to Koch's postulates, for bacterial pathogenesis, virulence. https://t.co/hIQGTI268W #AMP2016
9:21am November 11th 2016 via Twitter Web Client
LiPuma: Median CF survival now to late 20's. Predicted survival - mid 30's. #AMP2016
9:19am November 11th 2016 via Twitter Web Client
LiPuma: #AMP2016 CF progress tracked in '70 ref: https://t.co/bAhCR1HzKl Shows 'downward spiral' - obstruction, insuff, resp failure
9:18am November 11th 2016 via Twitter Web Client
LiPuma: #AMP2016 Sant'Agnese in '46 https://t.co/Yg0FMAqZnE started blowing Penicillin in lungs '57 and increase in survival
9:16am November 11th 2016 via Twitter Web Client
LiPuma: '42 penicillin available; respiratory tract Staph infection. '46 ref - ages of children who died of CF, all Staph aureus #AMP2016
9:14am November 11th 2016 via Twitter Web Client
LiPuma: 1938, described in pancreas, failure to thrive in infants, death w/in first year, a GI disease. '43 Farber resp tract #AMP2016
9:13am November 11th 2016 via Twitter Web Client
LiPuma:1:30 carrier freq of CF. 60K in US/EU. CFTR very large ion channel; CF multiple manifestations across organs #AMP2016
9:11am November 11th 2016 via Twitter Web Client
John LiPuma (Univ Michigan MI) The microbiome of Cystic Fibrosis #AMP2016
9:06am November 11th 2016 via Twitter Web Client
Mysorekar: Part 2 on Zika, reviews history and spread across US. New Nature ref https://t.co/AiFYwVtfG8 of mAb mouse vaccine #AMP2016
8:55am November 11th 2016 via Twitter Web Client
Mysorekar: Shows distribution across regions from this '16 ref https://t.co/Eg8QuMHBcI (Note - high level of unk in some areas) #AMP2016
8:43am November 11th 2016 via Twitter Web Client
Mysorekar: Two routes of where microbe may come from: vagina via cervix, or from diet; but are distinct when compared to HMP data #AMP2016
8:39am November 11th 2016 via Twitter Web Client
Mysorekar: Fetal Membrane (FM) lowest variability of 3 areas. Validated quantitation via qPCR to find copy number #AMP2016
8:35am November 11th 2016 via Twitter Web Client
Mysorekar: Did 16S rRNA sequencing, analysed with QIIME and Greengenes. Shows Shannon diversity score by location #AMP2016
8:34am November 11th 2016 via Twitter Web Client
Mysorekar: Fetal-derived epthelial cells called EVTs also carry microbes '14 ref https://t.co/6GRRkPQbXt #AMP2016
8:33am November 11th 2016 via Twitter Web Client
Mysorekar: Bacterial stains show spirochetes, rods, etc. Shows close-ups from '12 ref #AMP2016
8:31am November 11th 2016 via Twitter Web Client
Mysorekar: Placentas collected, FFPE, three different portions (basal plate BP, placental villous PV, fetal membrane FM) #AMP2016
8:30am November 11th 2016 via Twitter Web Client
