Deignan: Clin relevance may not be that impt in this context; much intrinsic variants in any smpl. Ex: EGFR Exon 19 del #FDANGSWorkshop
11:39am February 25th 2016 via Twitter Web Client
Hegde: A critical and sens. Q for a mfr. Numbers? Adequate testing (sens, spec) but how difficult to get smpl types #FDANGSWorkshop
11:37am February 25th 2016 via Twitter Web Client
Roscoe: To eval performance, what variants? Challenging parameters? Platform bias? How to represent this? LoD? #FDANGSWorkshop
11:35am February 25th 2016 via Twitter Web Client
Donna Roscoe (FDA): Seeing input on analytical perf with a representative var set may infer for an entire panel #FDANGSWorkshop
11:34am February 25th 2016 via Twitter Web Client
Van Allen: Mentions the fact that intense interest in immuno-oncology and neoantigens, will be missed by panels #FDANGSWorkshop
11:32am February 25th 2016 via Twitter Web Client
Van Allen: Inferring global genome properties from panel testing: from 300 gene panel and inferring mutational load #FDANGSWorkshop
11:31am February 25th 2016 via Twitter Web Client
Van Allen: Analysed many germline db's (including ExAC) 157 clinical exomes, modeled 300 genes, got 14% FP rate #FDANGSWorkshop
11:27am February 25th 2016 via Twitter Web Client
Van Allen: #FDANGSWorkshop The '15 Science Trans Med ref: https://t.co/AmfNNWZuf3
11:26am February 25th 2016 via Twitter Web Client
Van Allen: Tumor-only analysis - germline FP mutations. Velculescu at Hopkins reported 30-50% FPs are germlines #FDANGSWorkshop
11:25am February 25th 2016 via Twitter Web Client
Van Allen: Same BAM, 3 different approaches, only 2 of 100's overlap #FDANGSWorkshop
11:24am February 25th 2016 via Twitter Web Client
Van Allen: Contrasting to fusion detection: RNA based, showed a messy Venn diagram of prostate samples diff analysis #FDANGSWorkshop
11:23am February 25th 2016 via Twitter Web Client
Van Allen: Somatic mutation detection vs fusion det: point mutation calls MuTect paper https://t.co/CKrrGvchjH #FDANGSWorkshop
11:22am February 25th 2016 via Twitter Web Client
Eli Van Allen (Dana Farber CC) NGS Panels and bioinformatics strategies for oncology #FDANGSWorkshop
11:20am February 25th 2016 via Twitter Web Client
Hegde: Sample pooling needs to be addressed in validation. "Not a huge problem' 0.18% in library prep, 0.03% subsequent #FDANGSWorkshop
Hegde: LOD, sens and spec are 'absolutely critical'. If it cannot detect <10% 'it must be disclosed'. #FDANGSWorkshop
11:18am February 25th 2016 via Twitter Web Client
Hegde: Reprod and versatility with different specimen types, reporting add'l needs. #FDANGSWorkshop
11:16am February 25th 2016 via Twitter Web Client
Hegde: About 20 smpls for analytical validation, ~1000x coverage; VAF freq <20%. Strategic mixtures to get VAF 10% or less #FDANGSWorksho
Hegde: Approaches to validation: involve hetergeneous tissues, evidence-based selection of targets, VAF. #FDANGSWorkshop
11:14am February 25th 2016 via Twitter Web Client
Hegde: At 10^11 bases/run, systematic mutation detection of all mutation types, clear advantages of NGS #FDANGSWorkshop
11:12am February 25th 2016 via Twitter Web Client
Hegde: And SNV detection and indel / other mutation types (CNVs, SVs) bioinf approaches #FDANGSWorkshop
11:11am February 25th 2016 via Twitter Web Client
Hegde: Many points to consider re:Targeted panels. Capture method, specimen diffs, detection methods/filters #FDANGSWorkshop
11:09am February 25th 2016 via Twitter Web Client
Hegde: Ability for HTP sequencing to look at SNV, CNAs (indels, translocations). Drug repurposing for new cancer types #FDANGSWorkshop
11:08am February 25th 2016 via Twitter Web Client
Hegde: Points out difference between cancer vs rare disease: use of RNA and DNA, re-sampling #FDANGSWorkshop
11:07am February 25th 2016 via Twitter Web Client
Also R Klees (NY State DOH) First up Madhuri Hedge (Emory) Germline testing for mosaicism similar to oncology #FDANGSWorkshop
11:06am February 25th 2016 via Twitter Web Client
Panel 2: Analytical Validation and Bioin #FDANGSWorkshop M Hegde (Emory) E Van Allen (Dana Farber) J Deignan (UCLA) D eberhard (UNC)
11:04am February 25th 2016 via Twitter Web Client
A (Aisner): Tried unk smpls that needed orthogonal validation. Will use a small number of unk smpls, to guard against bias #FDANGSWorkshop
10:37am February 25th 2016 via Twitter Web Client
Q2: Commutability - do clin samples have to have a var? How many? A: (Pfeifer) >100 pt smples. Revalidation: dozens #FDANGSWorkshop
10:35am February 25th 2016 via Twitter Web Client
Pfeifer (con't): Have to stop talking about formalin fixation as the 'evil'; focus may be too narrow. One of may variables #FDANGSWorkshop
10:33am February 25th 2016 via Twitter Web Client
Pfeifer: Want reprod and accurate testing; formalin fixation time standardization may need to be done. (Horses, barns) #FDANGSWorkshop
10:32am February 25th 2016 via Twitter Web Client
Aisner (con't) Pathology at that level is a completely different level - many constraints, not feasible #FDANGSWorkshop
10:31am February 25th 2016 via Twitter Web Client
Open floor:Q: Could nucl acid sample claims be met by education of pathologist? A:(Aisner) - diverse pathologists #FDANGSWorkshop
10:30am February 25th 2016 via Twitter Web Client
Berger: Like the idea of in-silico validation, Since they can't test every possible variant. Mixing doesn't do CNV #FDANGSWorkshop
10:28am February 25th 2016 via Twitter Web Client
Luthra: Does the cell line reflect real-life samples? Heme malignancies - still need cell lines. Need large # of pt smples #FDANGSWorkshop
10:27am February 25th 2016 via Twitter Web Client
Pfeifer: Mentions dry-lab tests to look at bioinformatic sensitivity in analysis #FDANGSWorkshop
10:26am February 25th 2016 via Twitter Web Client
Pfeifer: Labs need to demonstrate extraction of nucleic acids of high quality. But where is the line drawn? #FDANGSWorkshop
10:25am February 25th 2016 via Twitter Web Client
Pfeifer: Looking for changes - cell lines can be mixed, often see the constituent components, unrelated to biology #FDANGSWorkshop
10:24am February 25th 2016 via Twitter Web Client
Schetter: Q4: How contrived samples may be used to demonstrate analytical validity. QC metrics, how to more closely mimic #FDANGSWorkshop
10:23am February 25th 2016 via Twitter Web Client
Rossi: For myeloma: enrichment for cells is critical. Specific input from hematopathologists #FDANGSWorkshop
10:22am February 25th 2016 via Twitter Web Client
Aisner: Bony specimens are handled specifically; communication streams impt for decalcification. Necrotic samples #FDANGSWorkshop
10:20am February 25th 2016 via Twitter Web Client
Pfeifer: And the ordering physician can't tell the difference of the limitations of a given test. #FDANGSWorkshop
10:19am February 25th 2016 via Twitter Web Client
Pfeifer: And another provider will provide a cheaper assay w/o any details on size of indels, other complexities #FDANGSWorkshop
Pfeifer: People will provide a test w/o specifying the kind of variants (i.e. rearrangements, translocations) #FDANGSWorkshop
10:18am February 25th 2016 via Twitter Web Client
Berger: 60 general types, 300 specific types, practical considerations. (Echos Raja's sentiments.) #FDANGSWorkshop
10:15am February 25th 2016 via Twitter Web Client
Schetter: Q3 Pan-Cancer claims - what kinds of studies needed for mfs to claim panels for different cancers #FDANGSWorkshop
10:13am February 25th 2016 via Twitter Web Client
Aisner: Yet constraints into what is submitted to the FDA, and what may accurately reflect the biology (vs the test) #FDANGSWorkshop
10:11am February 25th 2016 via Twitter Web Client
Schetter: The need is to accurately report what kind of CDx work has been done, and truthfully report that #FDANGSWorkshop
10:10am February 25th 2016 via Twitter Web Client
Pfeifer: And the primary vs. metastasis at a different site: different findings due to different sampling. #FDANGSWorkshop
10:06am February 25th 2016 via Twitter Web Client
Pfeifer: Where is the tumor sampled? Wonders if the FDA is thinking about this; studies are doing multiple sampling #FDANGSWorkshop
10:04am February 25th 2016 via Twitter Web Client
Rossi: Need to get pathologists to get involved 'from the very beginning'. #FDANGSWorkshop
Aisner: Labs that are not enriching for (tumor cellularity) need to look at this. Remnant material retained to go back to #FDANGSWorkshop
10:01am February 25th 2016 via Twitter Web Client
