Vilain: Idea is WGS-negative pts could 'soon be integrated into the overall diagnostic strategy' #AGBT17
9:29pm February 14th 2017 via Hootsuite
Vilain: Conclude current NGS technology unable to investigate large structural changes in the genome. #AGBT17
9:28pm February 14th 2017 via Hootsuite
Vilain: EZH2 causes Weaver syndrome (overgrowth disorder), so potential clinical result. #AGBT17
Vilain: Last case, 13yo cauc. female, WGS trio; found EZH1 de-novo 1.6kb deletion. Never shown to be clinical disease, but... #AGBT17
9:27pm February 14th 2017 via Hootsuite
Vilain: Explained microcephaly, brain atrophy. Father was heterozygous; mother gave two deep intron variants. 'Tantalizing' cmpd het #AGBT17
9:25pm February 14th 2017 via Hootsuite
Vilain: Looking at undiagnosed pts, WES not coming up with Dx; found 3.5kb deletion shared by affected children in MED17 gene #AGBT17
9:24pm February 14th 2017 via Hootsuite
Vilain: 'the first molecular Dx on Saphyr platform' #AGBT17
9:20pm February 14th 2017 via Hootsuite
Vilain: PCR and WES neg, RNA-seq of muscle tissue showed exon 37 drop-off. Map showed 5.1MB inversion causing DMD (!) #AGBT17
9:19pm February 14th 2017 via Hootsuite
Vilain: Looked at DMD; each case could ID structural variant w/this next-generation mapping. 1 case, clear. 2nd case: DMD-like #AGBT17
9:18pm February 14th 2017 via Hootsuite
Vilain: Bionano also shows translocations, repeats differences. Goal - to discover novel pathogenic structural vars after WES #AGBT17
9:17pm February 14th 2017 via Hootsuite
Vilain: Views it as a complementary diagnostic - short read NGS, long read NGS, aCGH. Saphyr: 150kb - 2.5Mbp. indels, inversions #AGBT17
9:16pm February 14th 2017 via Hootsuite
Vilain: Throughput is 1 WGS/day. 90% sens for large indels, transversions. Goes quickly through workflow, from sample prep to image #AGBT17
9:15pm February 14th 2017 via Hootsuite
Vilain: Their results were published in JAMA '14 https://t.co/kMuOq6eqNA Novel approach - @bionanogenomics Saphyr (new system) #AGBT17
9:14pm February 14th 2017 via Hootsuite
Vilain: Next: Molecular 'triage': dx by WES. Their success rate is 25%; 28% potential dx; 42% no sig var; 4% new gene discovery #AGBT17
9:12pm February 14th 2017 via Hootsuite
Vilain: Then sequence; result is low success rate, except in specific diseases with modest or no genetic heterogeneity #AGBT17
9:11pm February 14th 2017 via Hootsuite
Vilain: 1K known mutations cause developmental delay. Current flow: rare or common phenotype, clin history, add'l phenotyping #AGBT17
Eric Vilain (UCLA CA, onto Nat'l Childrens Med Ctr DC) Use of next generation mapping in undiagnosed genetic disorders #AGBT17
9:10pm February 14th 2017 via Hootsuite
Whelan: Plan on 500 samples. Able to get 23MB of sequence not covered in std data, median net gain of 16MB. Lost: extreme GC #AGBT17
8:55pm February 14th 2017 via Hootsuite
Whelan: Using 30kb+ MW DNA, 10X Genomics system. Running pilot on schizophrenia and bipolar sequencing, Af American 50 smpls #AGBT17
8:52pm February 14th 2017 via Hootsuite
Chris Whelan (Broad Inst MA) Exploring 50 whole genomes with linked reads #AGBT17
8:50pm February 14th 2017 via Hootsuite
Q: Scaling system? Goto: (Unclear on the answer at this point, how well this method can scale.) #AGBT17
Q: The pore is close to atomic dimension; will it change dimension? Goto: Haven't observed these effects #AGBT17
8:47pm February 14th 2017 via Hootsuite
Goto: Data generated with tag sequence, and adenine homopolymer, DNA speed calc from intervals of tag; showed 100bp/sec data #AGBT17
8:42pm February 14th 2017 via Hootsuite
Goto: Motion-control at nm-scale: piezo actuator using laser doppler inferometry, showed 34nm/s speed or 100bp/sec #AGBT17
Goto: Looking at spatial resolution: five A's and a C, then 5 A's and a C. Showing signal histogram, four-mer resolution #AGBT17
8:41pm February 14th 2017 via Hootsuite
Goto: Shows homopolymeric signals, and blockade current's ability to discriminate between the four bases. #AGBT17
Goto: Showed 1.5nm, 2.4nm and 3.1nm pored via TEM images. #AGBT17
Goto: Use dielectric breakdown for nanopore fabrication. Can tune to target molecular size; accuracy of +/- 0.3nm (300pm!) #AGBT17
8:40pm February 14th 2017 via Hootsuite
Goto: Will talk mainly about sensing and motion control system (on the nanometer scale). Showed photos of LSI on wafer, and membrane #AGBT17
Goto: Using both modes - forward and reverse reads. Shows system concept, w/arrayed nanopore device on top of LSI circuit #AGBT17
Goto: Can do direct motion control - piezo actuator wtih mechanical (!) control. Can pull-down, and reverse to pull-up (!) #AGBT17
8:39pm February 14th 2017 via Hootsuite
Goto: Precise control of speed is impt for this method to work. They have developed SiN, 2.6nm thin membrane, on an 8-inch wafers #AGBT17
Goto: Points out Hitachi's development of ABi's 3730. Shows blockade current through solid-state, w/discrete signal pattern #AGBT17
8:38pm February 14th 2017 via Hootsuite
Goto: Shows short tandem repeats: ACACAC, ATCATC, AGTCAGTC: shows different blockage signals that can discriminate between 3 types #AGBT16
8:37pm February 14th 2017 via Hootsuite
Goto: Data generated with tag sequence, and adenine homopolymer, DNA speed calc from intervals of tag; showed 100bp/sec data #AGBT16
8:36pm February 14th 2017 via Hootsuite
Goto: Motion-control at nm-scale: piezo actuator using laser doppler inferometry, showed 34nm/s speed or 100bp/sec #AGBT16
8:35pm February 14th 2017 via Hootsuite
Goto: Looking at spatial resolution: five A's and a C, then 5 A's and a C. Showing signal histogram, four-mer resolution #AGBT16
8:34pm February 14th 2017 via Hootsuite
.@shgoodwin1 This talk is off the hook! Wild stuff!
8:33pm February 14th 2017 via Hootsuite in reply to shgoodwin1
Goto: Shows homopolymeric signals, and blockade current's ability to discriminate between the four bases. #AGBT16
8:33pm February 14th 2017 via Hootsuite
Goto: Showed 1.5nm, 2.4nm and 3.1nm pored via TEM images. #AGBT16
8:32pm February 14th 2017 via Hootsuite
Goto: Use dielectric breakdown for nanopore fabrication. Can tune to target molecular size; accuracy of +/- 0.3nm (300pm!) #AGBT16
8:31pm February 14th 2017 via Hootsuite
Goto: Will talk mainly about sensing and motion control system (on the nanometer scale). Showed photos of LSI on wafer, and membrane #AGBT16
8:30pm February 14th 2017 via Hootsuite
Goto: Using both modes - forward and reverse reads. Shows system concept, w/arrayed nanopore device on top of LSI circuit #AGBT16
8:29pm February 14th 2017 via Hootsuite
Goto: Can do direct motion control - piezo actuator wtih mechanical (!) control. Can pull-down, and reverse to pull-up (!) #AGBT16
8:28pm February 14th 2017 via Hootsuite
Goto: Precise control of speed is impt for this method to work. They have developed SiN, 2.6nm thin membrane, on an 8-inch wafers #AGBT16
8:27pm February 14th 2017 via Hootsuite
Goto: Points out Hitachi's development of ABi's 3730. Shows blockade current through solid-state, w/discrete signal pattern #AGBT16
8:26pm February 14th 2017 via Hootsuite
Yusuke Goto (Hitachi Ltd Japan) Solid state nanopore DNA sequencing: single-nucleotide discrimination and bidir. DNA translocation #AGBT17
8:24pm February 14th 2017 via Hootsuite
Can it be accessed now? Weile: Last stages of writing a paper and db to make it available #AGBT16
8:23pm February 14th 2017 via Hootsuite
Weile: Predict may be able to get to 57% of human disease genes with all these approaches. Est cost for a 500aa protein $5K #AGBT16
8:21pm February 14th 2017 via Hootsuite
Weile: How far can they go? 3970 disease genes, 5% have gene in yeast. 29% of disease genes in human cell culture. Also Y2H assay #AGBT16
8:20pm February 14th 2017 via Hootsuite
