LIVE — Plenary Session 2015 BioIT, April 22, 2015, 8:00 – 10:00AM – Cambridge HealthTech Institute’s 14th Annual Meeting BioIT World – Conference & Expo ’15, April 21 – 23, 2015 @Seaport World Trade Center, Boston, MA
Dr. Aviva Lev-Ari will be in attendance on April 21, 22, 23
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April 22, 2015 * 8:00 – 9:45 am
8:00 Chairperson’s Opening Remarks
Phillips Kuhl, Co-Founder and President, Cambridge Healthtech Institute
8:05 Plenary Session Introduction
Jason Stowe, CEO, Cycle Computing
LIVE – Introduction
Use computing to answer tough question – by building infrastructure – for acceleration of Science
@Novartis:
Cancer Drug Design: Scientists need 50,000 cores – not available in house
10,000 Servers — 40 years of computing in 3 conpounds deployed in 8 hours — Amazon web servers — For $4300 the data run and turned off. Scientists need 10 servers — workflow is critical — accelerate the access to computing WHEN IT IS NEEDED, scalable computing iterative process
720 hours of Computing = 720 analysis,computing analysis — iterative process
Computer burset = Data Workflow
Chris applies multidisciplinary research at Memorial Sloan Kettering
8:15 Precision Combination Therapy: Discover • Design • Deliver
Chris Sander, Computational and Systems Biology, Memorial Sloan Kettering Cancer Center
LIVE
Algorithms are tailored — application to Cancer if that will be solved — to eliminate lasions and to PREVENT BY STRENGTHENING THE HUMAN IMMUNE SYSTEM
Genetic alterations — upregulate protein kinase – relpse
Best success in Melanoma identification of the mutations treatment with protein kinese tumor become resistNT AS IT REAPPEARED
SYSTEM BIOLOGY – DRUG — RESISTENCE — DRUG — RESISTENCE
ONE TO ONE DRUG BLOCK THE EXIT BY COMBINATION COMPOUNDS,
USING STRUCTURAL BIOLOGY TO DESIGN DRUGS —
- what combination to use – Pretubation biology of cancer cellline
- clinical trial on groups of patients
- Deliver personal therapy based on patient data – Precision Medicine
- Drug combinations network inference
perturb — measure — infer — predict
Pertubation Cell Biology: Not new – Response profile
– small Western Blots
– medium Chip Blots 50,000 data points
– large – Reverse Phase Protein Arrays (RPPA)
- Perturb
- Measure
- infer
Data drives network inference: Protein profiling Protein response to cancer cell lines to drug pertubation
Network models – best optimized what?
10,000 numbers non-linear: Infer optimal network models from pertubation data – OPTIMAL FITTING LOW PENALTY FOR OVER FITTING
— solution space is huge
Statistical Physics – a Matrix of probability distributions
Aproximation – vs experimental data
BP – Belief Propagation —
Systematic pertubations of RAFi resistant melanoma — probability distribution
Prediction from Pertubation — ONE drug
Phospho-protein and cell pphynotyoe
Inferred interaction model
two best combinations
BRAF V600E for Mel133
MEK – BRAF
BRD4
Predict combination: Synergy of inhibition of cMyc and MEK/REF Experimental Test:
Inhibition
DISCOVERY – DESIGN – DELIVERY — Apply pertubation to SYSTEM BIOLOGY
- Kidney Cancer
- Sarcome
- Melanoma
- Glioblastoma
- Prostate
- Pancreatic
- PLK1, STAT,
PLK1 Inhibitor – concentration of drug — a very small amount has impact BEFORE RESISTENCE IS DEVELOPED IN ONE YEAR OF START OF TREATMENT
- Biological reality — transcripts – protein – phenotype
- Abstraction/Model — math representation
- Applications — Prediction Interpretation Connect —>>> Therapy
Phynotype and solution in softward for data analysis
The Cancer Genome Atlas – TCGA 2008 – 2015
Cancer Genomics – 20K tumor samples from 98 Cancer studies
Simplicity & Power
Oncogenic SIgnature Classes
Protein Mutation vs copy number genetic alterations
Patients Groups and Drugs
PORTAL for MDs – contain 21,000 Tumors — Open Source used by researchers : cBioPortal for Cancer Genomics for phynotypes as a guide based on susrvival data of alteration and aggregation in tumor samples
One patient — all nucleiotid at different type intervals
Evolution genotype to phynotype: from amino acid sequence to 3D Structure of protein
transmembrane proteind – crystalographers on structure
Genetics from Sequencing to Structural Biology: Development and evolutions
Fold proteins from seuences Protein complexes from sequences
With Debra Marks Lab – Harvard MS
EVfold.org
EVcomplex.org
9:00 Benjamin Franklin Award & Laureate Presentation
RECEPIENT: Owen White, Director of Bioinformatics, Institute for Genome Sciences, University of Maryland, Baltimore, School of Medicine
Laureate Presentation
Biological compounds from liver passed to the gut – metabolism is in more bacterial cells in the gut then in the human cells
WGS of 100 million reads – Sample from the gut
Healthy Human Microbiome: Biochemicala pahtways
Inside the body — different bacteria
Sampls: Nares, Oral Vegina,
NIH MICROBIOME PROJECT
TCGA vs SRA Microbiome Data bases vd Google’s Content
Data Uncertenty
- Origin, library prep, nucleic acid prep
- publication ?
- metadata matters
- SRA: is data from a Cancer Pt of a Health Pt.
- NCBI BioSample Database — Accessing data and sharing
Go to The ONION –
ICD-9 DIagnosis COde Reference CHart
STANDARD development for dta – diversity in Biomedical data
Semantic and conceptual agreement is key
Challanges:
- COmmunity Members
- Communication
- Collaborative
- DO COmmunity — DIsease Ontoloty
- ICD9 vs Mesh vs OMIM NCI, DSM-5
- Phenotypic Description – Melissa Haendel
- Genotype
Regularization
Meta dat — all dat except of sequencing data
Expression Studies
Gene Ontology – Michell Gwinn
Evidence Ontology – Mark at Univeristy of Maryland, BLAST evidence used in manual assertion: WHat was done based on experimentation vs curation
Publishers are now recognizing Phynotypes — attracts more eyeballs to the site
Microbiome — in the process of annotation
9:30 Best Practices Awards Program – Editor-in-chief BioIT World
- Clinical & Health IT WInner
GSK with Epidemico – Project CRAWL
- IT Infrastructure Winner
UC Santa Cruz
- Informatics
Biogen Idec – deCODE
- Research & Discovery Finalists
AstrzZeneca
Pfizer
The WINNER — UCB BioPharma with EPAM Systems
- Knowledge Management Finalists
WINNER: European Lead Factory COnsortia with BIOBIA – Science Cloud: A Scientific Informatics Systems
- Gadges
Michael J Fox Foundation
tranSMART open data repository for Parkinson’s Disease Research
- Editor’s Choice
NIH Undiagnosed Diseases Program with Appistry
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