June 2015

Garlick:Q:Cost an issue; how about spike-in control? A:Planning to do with ctDNA and plasma, not with FFPE tissues though #TCGC15

4:13pm June 23rd 2015 via Hootsuite

Garlick:Q:Brings up fetal aneuploidy paper; not intended use (i.e. non-pregnant sample for aneuploidy) A:Accepted - made the news #TCGC15

4:12pm June 23rd 2015 via Hootsuite

Garlick: Summary - LDT to IVD transition will require multiple QC tools. #TCGC15

4:10pm June 23rd 2015 via Hootsuite

Garlick: Maternal bckgnd, fetal fx from trophoblasts. DNA stabilized, put into plasma. T21 linearity shown. Commutable matrix #TCGC15

4:08pm June 23rd 2015 via Hootsuite

Garlick: Same principles to ctDNA, dev. non-invasive prenatal screening product (Aug). T13, T18 and T21, 4-8% fetal fx. 2-14% perf. #TCGC15

4:07pm June 23rd 2015 via Hootsuite

Garlick:Plans to do germline controls with same method. Can get multi-site proficiency. Developing NGS-char FFPE tissues #TCGC15

4:05pm June 23rd 2015 via Hootsuite

Garlick: Variability over time: Levey-Jennings plot, 28 runs over 8 mo: specific mutations. #TCGC15

4:04pm June 23rd 2015 via Hootsuite

Russell Garlick at #TCGC15 talking about @SeraCare and Levey-Jennings plots http://t.co/kMELnMOKjv

4:04pm June 23rd 2015 via Hootsuite

Garlick: Some assay differences between AmpliSeq cancer panel and TruSeq on the MiSeq. CV's at 5%. Shows linearity at 10%, 15% etc #TCGC15

4:01pm June 23rd 2015 via Hootsuite

Garlick: Goal to challenge seq and pipelines. Performance of two assays - hyb-based vs. AmpliSeq, shows PCR dropout #TCGC15

3:59pm June 23rd 2015 via Hootsuite

Garlick: Constructs have been sequenced, quantitated via digital PCR, spiked into background of GIAB genomic DNA. Adjust allele freq #TCGC15

3:58pm June 23rd 2015 via Hootsuite

Garlick:Q:6-bp tag affects alignment? A:Can be specifically searched for and awareness of it helps analysis #TCGC15

3:57pm June 23rd 2015 via Hootsuite

Garlick: 6-bp engineered Internal Quality Marker included. Synthetic target in wild-type background gDNA. Showed del next to 6bp #TCGC15

3:55pm June 23rd 2015 via Hootsuite

Garlick: Seraseq product developed based upon Frederick Nat'l Lab for Cancer Research (NCI), CRADA for co-development #TCGC15

3:53pm June 23rd 2015 via Hootsuite

Garlick: 'There will be assay drift over time' - sensitivity, accuracy, reprod, LOD needs to be assessed #TCGC15

3:52pm June 23rd 2015 via Hootsuite

Garlick: 12 QC metrics - lots of variability in front-end. For oncology assays - only 2y ago 50 genes; today 613. #TCGC15

3:51pm June 23rd 2015 via Hootsuite

Garlick:Intention is to take these materials to the FDA. One paper 6/8 labs got this test correct http://t.co/NAFLLs2i0x #TCGC15

3:49pm June 23rd 2015 via Hootsuite

Garlick: Pressures of cost - but what metrics matter? What drifts over time? W/o standards over time, an unknown. #TCGC15

3:47pm June 23rd 2015 via Hootsuite

Garlick: NGS transition to clinical assays - from 40 to perhaps 250 labs in 2y: targeted gene panels, some WES, fusion RNA #TCGC15

3:46pm June 23rd 2015 via Hootsuite

Garlick: Oncology, biosynthetic details, some data from PDX (patient-derived xenografts), #TCGC15

3:46pm June 23rd 2015 via Hootsuite

Garlick:5-10% allele freq, ID driver genes. Reagent changes, pipeline changes, instrument changes - all need new controls #TCGC15

3:44pm June 23rd 2015 via Hootsuite

Garlick: For LDTs, CLIA says every assay needs a control. Clin labs are under pressure to reduce costs; QC challenges the same. #TCGC15

3:43pm June 23rd 2015 via Hootsuite

Garlick: Today focuses on NGS; new knowledge, new tests. Still needs quality control to assess drift; principles 'don't change' #TCGC15

3:42pm June 23rd 2015 via Hootsuite

Garlick: SeraCare makes products for the IVD industry; started in the '80's to protect the blood supply (HCV, HIV). #TCGC15

3:41pm June 23rd 2015 via Hootsuite

Russell Garlick (@seracare) "Seraseq quality controls for genomic analysis" #TCGC15

3:40pm June 23rd 2015 via Hootsuite

Correll:Q:What if 3 sep reports are ordered? Standardization? A: They see differences in quality across labs, but also similarities #TCGC15

3:26pm June 23rd 2015 via Hootsuite

Regarding yesterday's van 't Veer #TCGC15 talk RT @malachigriffith: I-SPY 2: http://t.co/vf6VI4GnHf https://t.co/XSmxqOvnhs #GenomicTrials

3:18pm June 23rd 2015 via Hootsuite

Correll: Lower barriers to entry to clinical market. He and John Quackenbush founded Genospace (funded by Oracle) #TCGC15

3:10pm June 23rd 2015 via Hootsuite

Correll: Finding more we do understand, also finding more we don't. Clinical labs: use same tech, same genes, similar reports. #TCGC15

3:09pm June 23rd 2015 via Hootsuite

Mick Correll (Genospace) "Clinical laboratory medicine: from bench science to information science" #TCGC15

3:06pm June 23rd 2015 via Hootsuite

Diehn: Summary: ultimately needs a clinical trial to show effectiveness of this technology. #TCGC15

3:05pm June 23rd 2015 via Hootsuite

Diehn: Without prior knowledge of tumor mutation: limit is 0.4% (measured fraction), need to get down to 0.1%. Has paper under rev. #TCGC15

3:02pm June 23rd 2015 via Hootsuite

Diehn: Showed Stage IB pts and follow-up by tracking ctDNA for residual disease, 32 mos 0 pg/mL (detectable at 3 pg/mL) #TCGC15

3:00pm June 23rd 2015 via Hootsuite

Diehn: AF in tumor at 10%; in ctDNA only 1%. Tracked over time. Radiation treatment - scar or tumor? Prog tracked via ctDNA #TCGC15

2:57pm June 23rd 2015 via Hootsuite

Diehn: Relapse pt with T790M not detected by SNaPshot assay (sens at 10%) but found via CAPP-Seq Mut in tumor and ctDNA same #TCGC15

2:55pm June 23rd 2015 via Hootsuite

Diehn: Showed ROC curve, better at stage II-IV lung ca but still good. Monitored ctDNA in metastatic NSCLC Stage IV Nature Med '14 #TCGC15

2:50pm June 23rd 2015 via Hootsuite

Diehn: Can get to 0.01% detection, SNVs, indels, CNV and rearr's. A personalized biomarker. Shows importance of using multi-markers #TCGC15

2:47pm June 23rd 2015 via Hootsuite

Diehn: Methods chart: dPCR, Safe-SeqS, TAm-Seq cp to WGS/WES. They developed CAPP-Seq. ID'd spec regions per class of cancer #TCGC15

2:42pm June 23rd 2015 via Hootsuite

Diehn: ctDNA by tumor-spec muts, can look at methylation, LOH. Challenge is low amt '14 Nature Med http://t.co/xxUF1HP04E #TCGC15

2:39pm June 23rd 2015 via Hootsuite

Diehn: cell-free DNA typically is 80-90% from hematopoietic cells. cfDNA has size distribution mode around 160bp. #TCGC15

2:36pm June 23rd 2015 via Hootsuite

Diehn: Distinguishes between CTCs and ctDNA Fig from '13 ref http://t.co/lEmTtBAEZ0 5ng /mL plasma <2h half-life, changes w/trauma #TCGC1

2:35pm June 23rd 2015 via Hootsuite

Diehn: Liquid biopsies have many potential advantages - ID MRD, prognostic or predictive tests, early detection of recurrence #TCGC15

2:32pm June 23rd 2015 via Hootsuite

Maximilian Diehn (Stanford Univ) "Ultrasensitive detection of circulating tumor DNA by deep sequencing" #TCGC15

2:30pm June 23rd 2015 via Hootsuite

Pasaniuc:Missing heritability: DNAse marks, histone methylation analyzed for enrichment of probability of having causal variants #TCGC15

2:22pm June 23rd 2015 via Hootsuite

Pasaniuc: Looking at ENCODE - overlapping GWAS signals to eQTLs Nicolae 2010 http://t.co/yEsMIeS3Q5 '12 DHS http://t.co/9NVKfz49sI #TCGC15

2:12pm June 23rd 2015 via Hootsuite

Pasaniuc: Figure from Goh et al 2012 ref http://t.co/kzD2867ORE 42K iCOGS, 7K BPC3, 10K AAPC studies, all linked to TGP #TCGC15

2:02pm June 23rd 2015 via Hootsuite

Pasaniuc: Pr ca with 100 GWAS loci only explains 33% of familial risk 2014 meta-analysis http://t.co/xlBcoLyb8b #TCGC15

1:59pm June 23rd 2015 via Hootsuite

Bogdan Pasaniuc (UCLA) "Integration of genetic and epigenetic data to understand genetic risk of prostate cancer" #TCGC15

1:57pm June 23rd 2015 via Hootsuite

Jackson: Late-stage lung ca pt, Tarceva resp, relapse, then TreatmentMAP, went from ECOG 3 to 1-2 after rec'd treatmnt #TCGC15

1:22pm June 23rd 2015 via Hootsuite