Schloss: Acknowledges series of technologies they helped directly develop - Roche, Solexa, Agencourt, Helicos, Polonator.... #AGBT14
9:20am February 15th 2014 via Hootsuite
Schloss: Shows list of grantees, including NabSys, VisiGen and ILMN. '05 NGHRI release with some. http://t.co/D3SgiG3Vn7 #AGBT14
9:19am February 15th 2014 via Hootsuite
Schloss: NHGRI's initial RFA's - in 2004. The Scientist article from 2004 describing it: http://t.co/0R1Pc3rZyz #AGBT14
9:16am February 15th 2014 via Hootsuite
Schloss: Showing plot (y-axis 'per finished bp'): $10 in 1990, ~$0.02 in 2005. HGS about $50M. ID the need for 'quantum leaps'. #AGBT14
9:14am February 15th 2014 via Hootsuite
Up first: Jeffery Schloss, NHGRI: Ambitious Goals, Concerted Efforts, Conscientious Collaborations – 10 Years Hence
9:13am February 15th 2014 via Hootsuite
A pleasure to meet @bffo, @splon, @deannachurch, @hollihdilks, @CRIgenomics and @lexnederbragt in person here at #AGBT14 - All great folks.
9:12am February 15th 2014 via Hootsuite
Thanks to @CRIgenomics James generously gave me these QuantStudio 3D digital PCR links he made. http://t.co/R5MSkEmv8h #AGBT14
8:03am February 15th 2014 via Hootsuite
Zhu: Q: Unique to T-cell activation? A: Proteasome controls cell-cycle; macrophage and other cells but intron ret. different #AGBT14
9:32pm February 14th 2014 via Hootsuite
Zhu: Concl: Intron retention coupled w/ RNA degradation may serve as a global mechanism to regulate gene expression #AGBT14
9:31pm February 14th 2014 via Hootsuite
Zhu: Cp of human to mouse - same effect of intron retention effect upon activation. #AGBT14
9:28pm February 14th 2014 via Hootsuite
Zhu: Now looking at porteasome genes' intron retention reduction upon T-cell activation, both via RNA-Seq and ChIP #AGBT14
RT @lexnederbragt: Nature News: Oxford Nanopore unveils data from portable genome sequencer http://t.co/z7ovBnpgNC #agbt14
9:23pm February 14th 2014 via Hootsuite
Zhu: Higher IRI (intron-retained genes): promiscuous Pol II & H3K36me3 occupancy #AGBT14
9:22pm February 14th 2014 via Hootsuite
Zhu: Developed an intron retention index (ratio of shared introns / shared exons); separated naive, CM and EM T-cells #AGBT14
9:19pm February 14th 2014 via Hootsuite
Zhu: Intronic reads reduce upon activation; from 13.8% to 6.9%. But made more complex by alternative splicing events. #AGBT14
9:18pm February 14th 2014 via Hootsuite
Zhu: Using 100 ChIP-Seq datasets: looking at strand-spec RNA-Seq, looking at >100M reads; resting T-cell have high intronic reads #AGBT14
9:17pm February 14th 2014 via Hootsuite
Zhu: Looking at T-cell activation using CD3 + CD28; after activation divide, secrete cytokines to regulate / assist immune resp. #AGBT14
9:16pm February 14th 2014 via Hootsuite
Zhu: Reviewing histone marks for active and repressed genes; H2a.Z, etc. Correlate to gene expression changes. #AGBT14
9:15pm February 14th 2014 via Hootsuite
Up next: Jun Zhu, NHLBI. “Global Intron Retention: A Novel Gene Regulatory Mechanism During T Cell Activation” #AGBT14
9:13pm February 14th 2014 via Hootsuite
Hall: Q:Mobile element insertion in lit. - why? A: Work to support it is hard to contradict at present. #AGBT14
9:12pm February 14th 2014 via Hootsuite
Hall: No correlation w/ genes or functional elements; no evidence either of transposon-mediated activity #AGBT14
9:09pm February 14th 2014 via Hootsuite
Hall:No recurrent events - no evidence of programmed rearr. in the brain. #AGBT14
9:08pm February 14th 2014 via Hootsuite
Hall: 3 complex rearr. from six neuronal genomes; but one with 10 breaks in 10.4MB reminiscent of chromothrypsis #AGBT14
Hall: Difference in mice at 3 ages - est. 50/year, 3k per neuron by age 60? Interesting question. #AGBT14
9:07pm February 14th 2014 via Hootsuite
Hall: (But highly var genomes were selected against.) Mut rate can be est. from # of divisions. Est. 7x - 30x higher cp to germline #AGBT14
9:06pm February 14th 2014 via Hootsuite
Hall: Est 89-167 muts / neuron. Most mut's arise late in development. None found in more than 1 cell. No highly variant genomes. #AGBT14
9:05pm February 14th 2014 via Hootsuite
Hall: First proof that mature post-mitotic neurons can be reprogrammed and cloned. "It took her 40y to do this" #AGBT14
9:04pm February 14th 2014 via Hootsuite
Hall: Cloned old-fashioned via somatic nuclear transfer. 1-3% efficient. Six lines, 40-60x coverage seq. SNVs, indels, CNVs #AGBT14
9:03pm February 14th 2014 via Hootsuite
Hall: With Baldwin's lab at Scripps: cre-lox in olfactory nodule neurons, representative of others, exit cell cycle and don't divide #AGBT14
9:02pm February 14th 2014 via Hootsuite
Hall: One of his most frustrating studies: how to validate, and further investigate? No clonal relationships. Very low-res. #AGBT14
9:01pm February 14th 2014 via Hootsuite
Hall: Some have high (8 or 10) CNVs, 'look shattered'. Not really seen in fibroblasts. #AGBT14
Hall: 110 single neuronal genomes: all CNVs found in single neurons no 'hotspots'. Developed later in development. Most zero, 1 CNV #AGBT14
9:00pm February 14th 2014 via Hootsuite
Hall: Find CNVs of 3-6MB long. Published Science 2013 http://t.co/kxc4sNQ6NL #AGBT14
8:58pm February 14th 2014 via Hootsuite
Hall: Developed own protocol, had help: used GenomePlex (Sigma) (only 1-5% of genome - ?) Nextera, 1-5m reads, map CNVs #AGBT14
8:57pm February 14th 2014 via Hootsuite
Hall: Many hypothesize that neurons that have mut.-prone genomes. Aneuploidy, transposons, elevated activity may cause DNA breaks #AGBT14
8:55pm February 14th 2014 via Hootsuite
Hall: Looking at somatic mutation in brain. Why: we know little about it; medical relevance in cancer, mosaic disorders. #AGBT14
8:54pm February 14th 2014 via Hootsuite
Up next: Ira Hall, University of Virginia: The Landscape of Somatic Genome Variation in Single Neurons #AGBT14
8:53pm February 14th 2014 via Hootsuite
Hoischen: BWA, trimming, Sam-to-Bam, GATK pipeline. 26/42 genes LoF events: 19 >2 LoF; 7 1 LoF. 95% validated via Sanger #AGBT14
8:45pm February 14th 2014 via Hootsuite
Hoischen: 2x384 samples / week; only 100ng needed, 2x101 PE HiSeq reads; 304x ave coverage #AGBT14
8:44pm February 14th 2014 via Hootsuite
Hoischen: Used 42 new candidate ID genes, 2,501 MIP probes; from their NEJM paper here. http://t.co/xXyQWkOE0A #AGBT14
8:42pm February 14th 2014 via Hootsuite
Hoischen: Using MIP probes for their targeted sequencing. O'Roak Science ref http://t.co/tmVXJ64Fg4 #AGBT14
8:40pm February 14th 2014 via Hootsuite
Hoischen: Add'l 800 cases: 3 novel ID genes then identified. For the rest of the candidates? Go to the literature #AGBT14
8:37pm February 14th 2014 via Hootsuite
Hoischen: 100 patient-parent trios with severe intellectual disability (IQ < 50). Discovered 19 cand. genes #AGBT14
8:36pm February 14th 2014 via Hootsuite
Hoischen: More common disorders, a larger target w/ many genes; de novo disorders may also play a role in common disorders too #AGBT14
8:34pm February 14th 2014 via Hootsuite
Hoischen: De novo mutations - very or extremely rare. 10 or 100 cases: only 1 gene, the target is very small. #AGBT14
8:33pm February 14th 2014 via Hootsuite
Up next: Alexander Hoischen, Radboud University. MIP-Based Resequencing Identifies Recurrently Mutated Genes in Intell. Disability #AGBT14
8:32pm February 14th 2014 via Hootsuite
Sen: Q: Is the gene also in LD with others? A: Not a causal variant, no xcr binding sites. #AGBT14
8:31pm February 14th 2014 via Hootsuite
Sen: Q (Plon): Why not start with the eQTL? A: Exome, RNA-Seq started with. #AGBT14
Sen: Conclude: 'hypothesis generation research' - using phenotyped samples, genomic and transcriptome work #AGBT14
8:30pm February 14th 2014 via Hootsuite
Sen: No TREML4 signal distal to site of disease. Showed TREML4 produced by CD68 macrophage themselves. #AGBT14
8:28pm February 14th 2014 via Hootsuite
