Heath #AACR19 Engineered a single-chain tetramer, called signalling and antigen presenting bifunctional receptors (… https://t.co/RQ8ZfZeYgn
7:42am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Shows flow data that suggests low concentration of TCR. Back to tetramer approach (Schumaker group) -… https://t.co/BEwo22UWQ3
7:38am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Could be seeing low-binding affinity or low T-cell populations. KOKIKO - knock-out, (TCR) knock-in an… https://t.co/OjyjKZsygn
7:36am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Shows data from a poster at this conference; seeing T-cell populations via this sc method not seen by std tetramer-based flow.
7:34am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Kinetic study of neoantigen-spec PBMCs. Melanoma pt with anti-PD1 Rx; shows TILS at d187, shows CD8+… https://t.co/OmRz27um3n
7:30am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Fluorescent microscopy 'not a lot more painful than flow but a lot more sensitive'.
7:28am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Nanoparticle gives scaffold for 20k pMHC tetramers per particle (!) Can isolate via hemocytometry chi… https://t.co/hVwiaPR8KB
Heath #AACR19 Can use minigene approach, what antigens activated; or flow-based sorting; fastest is conditional ant… https://t.co/g5YbQqnC3O
7:27am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Part 2: Sensitive detection of antigen-spec T-cell populations and pairing of antigen-MHC with TCRa/b… https://t.co/u2TbJ0jCw1
7:26am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Knowledge of trajectories w/sc fluctuations, provides druggable targets for each trajectory.
7:24am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Concl of part 1: isogenic cells can take multiple indep trajectories to drug tolerance. Trying to det… https://t.co/TYOzeFnqKs
Heath #AACR19 If the two trajectories are indep: drugging of one type is indep of the other, and shows data PKM2i vs NFKBi.
7:23am April 2nd 2019 via Twitter Web Client
Heath #AACR19 (NB: I see from the slides that Dr. Heath is at the ISB in Seattle since 2018.)
7:21am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Shows time-lapse video of MITF-GFP high and MITF-GFP low, and a separation between states: 'no stocha… https://t.co/VpBcx37JsX
7:20am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Shows new statistical method similar to PCA, find two unbalanced processes.
7:17am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Analogy: 4 time-frozen snapshots of cars; never see the same car, but figure out trajectory of cars p… https://t.co/iubIug4ptb
7:15am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Get ave protein/metabolite, dispersion, and correlations between analytes. All done single-cell level… https://t.co/lr865btMqQ
7:13am April 2nd 2019 via Twitter Web Client
Heath #AACR19 From metabolic enzymes, metabolic regulators, sensitive state marker, resistant state marker, signaling transducer.
7:12am April 2nd 2019 via Twitter Web Client
Heath #AACR19 By day 3 of BRAFinh: chr is remodeled via atac-seq data. Chr6 NP1, Chr22. Can do targeted metabolomics. Shows metabolites
Heath #AACR19 Cell state changes: BRAFinh of pt-derived M397 triggers rapid cell-state dedifferentiation. Plastic t… https://t.co/vWCiQ4d0ub
7:10am April 2nd 2019 via Twitter Web Client
Heath #AACR19 Shows hetergeneous mix of cell compositions; shows images of one cell, any phenotype: regenerate tumor.
7:08am April 2nd 2019 via Twitter Web Client
Heath #AACR19 2 topics: adaptive resistance in melanoma, investigation into MHC
7:05am April 2nd 2019 via Twitter Web Client
James Heath (Caltech CA) #AACR19 New Single-Cell Methods for Oncology and Immuno-oncology
Braggio #AACR19 Conclude: very promising, all bulk seq vars were detected, very good correlation in VAF.
3:53pm April 1st 2019 via Twitter Web Client
Braggio #AACR19 Able to reconstruct tumor phylogeny in MBL to CLL progression. Showed scVAF compared to bulk VAF measured down to 1%.
3:51pm April 1st 2019 via Twitter Web Client
De Bono #AACR19 Reads/cell for 5 samples, both HiSeq and NovaSeq range from 10K to 37K/cell. About 150M reads per c… https://t.co/cHlnLNb0u9
3:48pm April 1st 2019 via Twitter Web Client
Braggio #AACR19 TP53 have unfavorable prognostic impact in CLL irrespective of (sub)clonal status.
3:44pm April 1st 2019 via Twitter Web Client
Braggio #AACR19 1-2% of pre-leukemic will become asymptomatic CLL every year. Watch and wait: another area where es… https://t.co/xztbqDwF7K
3:39pm April 1st 2019 via Twitter Web Client
Braggio #AACR19 Early results from n=5 so far of 500 patients. CLL - from pre-malignant to asymptomatic, to progres… https://t.co/0lpZOUIcF2
3:38pm April 1st 2019 via Twitter Web Client
Esteban Braggio (Mayo Clinic AZ) Single-Cell genomics studies in MBL and CLL
3:36pm April 1st 2019 via Twitter Web Client
Q: How to tell the 3% selected vs 97% unselected? Takahashi #AACR19 Did replicate sampling and found identical data.
3:35pm April 1st 2019 via Twitter Web Client
Q: What is the difference to MDA (WGA)? Method of phylogen tree? Takahashi: #AACR19 Targeted sc amplicon, error rat… https://t.co/oOloLobvqQ
3:33pm April 1st 2019 via Twitter Web Client
Takahashi #AACR19 Concl - not inferring clonal architecture, they can show it directly. Also lessons in technical l… https://t.co/tFOzBT5THq
3:31pm April 1st 2019 via Twitter Web Client
Takahashi #AACR19 74yo male, t-AML, BM blast 62%; treated w/azacitidine, sorefenib, remission. 9 mo relapse BM blas… https://t.co/XfklaoNTmC
3:29pm April 1st 2019 via Twitter Web Client
Takahashi #AACR19 Both divergent and convergent evolution demonstrated. Longitudinal samples - 20 cases. Shows tumo… https://t.co/bG23C8GPPF
3:28pm April 1st 2019 via Twitter Web Client
Takahashi #AACR19 Same exclusions of IDH1/2; also FLT3-ITD and FLIT3-TKD.
3:25pm April 1st 2019 via Twitter Web Client
Takahashi #AACR19 showing mutually exclusive muts: KRAS and NRAS do not co-occur. w/8K cells, statistically sig via Fisher's exact.
3:24pm April 1st 2019 via Twitter Web Client
Takahashi #AACR19 low-coverage solved by NextSeq, HiSeq w/higher coverage. Analysis of MAF LoD: Mission says 0.1%;… https://t.co/v5GmQ3OhAt
3:23pm April 1st 2019 via Twitter Web Client
Takahashi #AACR19 270K cells put in, only 3% get sequenced (7617 cels). Allele drop-out rate est. from SNP loci 8.7… https://t.co/4PbZui5Mgw
3:21pm April 1st 2019 via Twitter Web Client
Takahashi #AACR19 70 AML pts, 40 amplicons w/19 AML genes. Bulk NGS: >100% of muts were validated; SNP array confirmed zygosity.
3:20pm April 1st 2019 via Twitter Web Client
Takahashi #AACR19 From VAF alone of different mutations, you'll need longitudinal samples. Navin '11, Pellegrino '18 https://t.co/SmPnzbqt2R
3:18pm April 1st 2019 via Twitter Web Client
Takahashi #AACR19 More data today at 4pm in A-302 as well. Clonal heterogeneity - not linear, it is branched. '12 https://t.co/xROwr1SBXc
3:15pm April 1st 2019 via Twitter Web Client
Koichi Takahashi (MD Anderson) #AACR19 Unraveling clonal hetergeneity and evolutionary history of AML by sc DNA sequencing
3:13pm April 1st 2019 via Twitter Web Client
#AACR19 Beard: 500 samples x 5K cells = 2.5M datapoints. Have iterative QC data they get feedback on performance. T… https://t.co/1A7IMwGySr
3:12pm April 1st 2019 via Twitter Web Client
#AACR19 Beard: Amplicon design to 20k genes; platforms supported: MiSeq, HiSeq, NextSeq, NovaSeq. On-demand cloud tool.
3:08pm April 1st 2019 via Twitter Web Client
#AACR19 Beard: New chem is fast (faster TAT on custom), efficient (better uniformity), targeted w/higher plexy - from 300-500 now to 1000.
3:07pm April 1st 2019 via Twitter Web Client
#AACR19 Beard: Tapestri "the only targeted single-cell analysis platform'. Cell into droplets, joins to barcoded beads and reagents.
3:06pm April 1st 2019 via Twitter Web Client
#AACR19 @missionbio Nigel Beard, VP of R&D. 1/3 of us will experience cancer; 9B: est. population of the world in 2… https://t.co/nfKP3b
3:05pm April 1st 2019 via Twitter Web Client
De Bono #AACR19 CTC-STOP one publication https://t.co/1OA27UUO8u When possible: embed circ biomarkers into Ph I/II… https://t.co/CGUN5kN5tl
7:44am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Can avoid over-Rx. CTC-STOP trial: based only on CTC counts. Need to show clinical utility. https://t.co/149t9MrIl1
7:42am April 1st 2019 via Twitter Web Client