This document summarizes a presentation on genes and environment in personalized medicine. It discusses:
1) How existing databases of gene-disease associations are limited for applying genome sequencing results to an individual patient due to incomplete data.
2) A database called VARIMED that aims to address these limitations by curating over 12,000 papers and 192,000 SNPs and their associations with 4,400 diseases and phenotypes.
3) Challenges in moving from odds ratios to likelihood ratios for assessing disease risk based on genomic data and an individual's clinical information.
From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...Dexter Hadley
Lecture Objectives:
1) To use examples from my research to define and introduce the ideals of precision medicine and digital health. 2) To introduce how large scale population-wide analysis of data can be used to facilitate these two ideals. 3) To introduce how freely available open data can be used to facilitate these two ideals. 4) To show how mobile technology can be used to facilitate these two ideals.
From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...Dexter Hadley
Lecture Objectives:
1) To use examples from my research to define and introduce the ideals of precision medicine and digital health. 2) To introduce how large scale population-wide analysis of data can be used to facilitate these two ideals. 3) To introduce how freely available open data can be used to facilitate these two ideals. 4) To show how mobile technology can be used to facilitate these two ideals.
2015 09-14 Precision Medicine 2015, London, Alain van GoolAlain van Gool
Outline of my view hoe personalized health(care) is more than just targeted medicines, also including personal motivation and actions towards disease prevention. It also outlines 4 key factors that should be in order for optimal personalized health(care): 1. start with patients first, 2. Accelerate translation research to application, 3. Copy best practice, 4. Spread the word.
MT115 Precision Medicine: Integrating genomics to enable better patient outcomesDell EMC World
"The emergence of genomics and real-time screening is helping to transform the practice of medicine as we know it today. New technologies present improved ways to tackle health issues and what was once thought to be “untouchable” due to cost, timing or resources, is now achievable through genetic screenings and genome sequencing.
During this session, we will explore:
1. The benefits of incorporating a genomics strategy early in lifeline
2. The Precision Medicine Initiative – how does this help? Does this encourage more people to get genetic screenings?
3. What’s involved in a genetic screening
"
The Uneven Future of Evidence-Based MedicineIda Sim
An Apple ResearchKit study enrolled 22,000 people in five days. A
study claims that Twitter can be used to identify depressed patients. A computer program crunches genomic data, the published literature, and electronic health record data to guide cancer treatment. The pace, the data sources, and the methods for generating medical evidence are changing radically. What will — what should — evidence-based medicine look like in a faster, personalized, data-dense tomorrow?
- Presented as the 3rd Annual Cochrane Lecture, October 2015 in Vienna, Austria.
Atul Butte's presentation to the Association of Medical School Pediatric Department Chairs #AMSPDC on March 3, 2018.
Some pre-publication data slides have been removed from this deck.
Evolutionary medical genomics, whether we realize it or not, is the foundation of genetics of predispositions whose main goal should not be personalized prediction of disease risk, but to develop strategies for its treatment and prevention on the basis of the knowledge of its genetic, evolutionary history and molecular mechanisms.
2015 09-14 Precision Medicine 2015, London, Alain van GoolAlain van Gool
Outline of my view hoe personalized health(care) is more than just targeted medicines, also including personal motivation and actions towards disease prevention. It also outlines 4 key factors that should be in order for optimal personalized health(care): 1. start with patients first, 2. Accelerate translation research to application, 3. Copy best practice, 4. Spread the word.
MT115 Precision Medicine: Integrating genomics to enable better patient outcomesDell EMC World
"The emergence of genomics and real-time screening is helping to transform the practice of medicine as we know it today. New technologies present improved ways to tackle health issues and what was once thought to be “untouchable” due to cost, timing or resources, is now achievable through genetic screenings and genome sequencing.
During this session, we will explore:
1. The benefits of incorporating a genomics strategy early in lifeline
2. The Precision Medicine Initiative – how does this help? Does this encourage more people to get genetic screenings?
3. What’s involved in a genetic screening
"
The Uneven Future of Evidence-Based MedicineIda Sim
An Apple ResearchKit study enrolled 22,000 people in five days. A
study claims that Twitter can be used to identify depressed patients. A computer program crunches genomic data, the published literature, and electronic health record data to guide cancer treatment. The pace, the data sources, and the methods for generating medical evidence are changing radically. What will — what should — evidence-based medicine look like in a faster, personalized, data-dense tomorrow?
- Presented as the 3rd Annual Cochrane Lecture, October 2015 in Vienna, Austria.
Atul Butte's presentation to the Association of Medical School Pediatric Department Chairs #AMSPDC on March 3, 2018.
Some pre-publication data slides have been removed from this deck.
Evolutionary medical genomics, whether we realize it or not, is the foundation of genetics of predispositions whose main goal should not be personalized prediction of disease risk, but to develop strategies for its treatment and prevention on the basis of the knowledge of its genetic, evolutionary history and molecular mechanisms.
"Hacking the Software for Life" - Brad Perkins (Chief Medical Officer, Human ...Hyper Wellbeing
"Hacking the Software for Life" - Brad Perkins (Chief Medical Officer, Human Logevity, Inc.)
Delivered at the inaugural Hyper Wellbeing Summit, 14th November 2016, Mountain View, California.
For more information including details of subsequent events, please visit http://hyperwellbeing.com
The summit was created to foster a community around an emerging industry - Wellness as a Service (WaaS). Consumer technologies, in particular wearables and mobile, are powering a consumer revolution. A revolution to turn health and wellness into platform delivered services. A revolution enabling consumer data-driven disease risk reduction. A revolution extending health care past sick care towards consumer-led lifelong health, wellness and lifestyle optimization.
WaaS newsletter sign-up http://eepurl.com/b71fdr
@hyperwellbeing
Dr Catherine Mercer and Dr Frank Ratcliff - The 100,000 Genome Project - Jan ...onthewight
The 100,000 Genomes Project will sequence 100,000 genomes from around 70,000 people.
Participants are NHS patients with a rare disease, plus their families, and patients with cancer. Significantly, this is currently the largest national sequencing project of its kind in the world.
This talk explores the project, and ask the question; “Would you have your genome sequenced?”
Bad reproducibility of experimental results becomes a systemic problem in biomedicine. One of the main reason of this is inadequate statistical analysis. Statistical analysis should be comprehensive harmonizing statistical evidences and predictions as well as frequentist and Bayesian approaches. It is insufficient to carry out the null hypothesis significance testing (NHST) reporting P-values. Statistical significance doesn’t mean clinical importance.
Effect size with confidence and prediction intervals should be reported. Experiments an/or observations should be repeated many-many times and their agreement should be investigated.
The best way is to repeat the experiments independently in different laboratories (in different countries).
"How Scientific Wellness will Drive The Future of Health" - Nathan Price (Pro...Hyper Wellbeing
"How Scientific Wellness will Drive The Future of Health" - Nathan Price (Professor, Institute of Systems Biology)
Delivered at the inaugural Hyper Wellbeing Summit, 14th November 2016, Mountain View, California.
For more information including details of subsequent events, please visit http://hyperwellbeing.com
The summit was created to foster a community around an emerging industry - Wellness as a Service (WaaS). Consumer technologies, in particular wearables and mobile, are powering a consumer revolution. A revolution to turn health and wellness into platform delivered services. A revolution enabling consumer data-driven disease risk reduction. A revolution extending health care past sick care towards consumer-led lifelong health, wellness and lifestyle optimization.
WaaS newsletter sign-up http://eepurl.com/b71fdr
@hyperwellbeing
John Ryals- Impacto de las ciencias ómicas en la medicina, nutrición y biotec...Fundación Ramón Areces
El 29 de marzo de 2016 celebramos un Simposio Internacional sobre el 'Impacto de las ciencias ómicas en la medicina, nutrición y biotecnología'. Organizado por la Fundación Ramón Areces en colaboración con la Real Academia Nacional de Medicina y BioEuroLatina, abordó cómo un mejor conocimiento del genoma humano está permitiendo notables avances hacia una medicina de precisión.
I am not an expert, but UCSF asked me to spout wisdom on Twitter, especially for the health, research, and academic community, so here's a slide deck I presented on September 10, 2019.
Remote presentation by Atul Butte at the NSTC Interagency Working Group on Biological Data Sharing on 2019-06-12.
The working group is charged by the National Science and Technology Council to develop a road map to enable robust sharing and maximize reuse of biological data, identifying opportunities for interagency coordination, and academic, industrial, and international partnerships. The workshop will bring together a diverse community of government, academic, and industrial stakeholders to identify key bottlenecks and challenges that interfere with the open exchange of information and to identify potential solutions that will accelerate biological science research.
Presentation for the CSIR Fourth Paradigm Institute Silver Jubilee (Bangalore...
2013 03 genomic medicine slides
1. Genes and Environment in
Personalized Medicine
Atul Butte, MD, PhD abutte@stanford.edu
Chief, Division of Systems Medicine, @atulbutte
Department of Pediatrics,
Department of Medicine, and, by courtesy,
Computer Science
Center for Pediatric Bioinformatics, LPCH
Stanford University
2. Disclosures
• Scientific founder and • Honoraria for speaking at
advisory board membership – Lilly
– Genstruct – Pfizer
– NuMedii – Siemens
– Personalis – Bristol Myers Squibb
– Carmenta • Speakers’ bureau
– None
• Past or present consultancy
– Lilly • Companies started by students
– Johnson and Johnson – Carmenta
– Roche – Serendipity
– NuMedii – NuMedii
– Genstruct – Stimulomics
– Tercica – NunaHealth
– Ansh Labs – Praedicat
– Prevendia – Flipora
– Samsung
5. Patient zero
40 year old male in
good health presents to his
doctor with his
whole genome
No symptoms
Exercises regularly
Takes no medications
Family history of
aortic aneurysm
Family history of
sudden death
Presents with 2.8 million SNPs
752 copy number variants
6
6. Existing SNP-disease databases are too limited
for application to a human genome
Genome-wide association studies
• NHGRI GWAS Catalog
– 1032 papers 5050 SNPs for 557 diseases (6280 records),
but 26% without OR, 33% without risk/protective alleles
Individual candidate-gene associations
• NIH Genetic Association Database
– 56,000 papers, 130,000 records, ~2000 genes, only 4% with
dbSNP ids, 1706 with alleles, none with risk/protective
• Online Mendelian Inheritance in Man
– Moving to dbSNP ids, monogenic
• Human Genome Mutation Database
– 113247 mutations, most Mendelian disease, few SNPs, no
genotypes, or odds ratios
7. • Study published in 2008 in
Inflammatory Bowel
Disease
• Crohn’s Disease and
Ulcerative Colitis
• Investigated 9 loci in 700
Finnish IBD patients
• We record 100+ items
– GWAS, non-GWAS papers
– Disease, Phenotype
– Population, Gender
– Alleles and Genotypes
– p-value (and confidence)
– Odds ratio (and confidence)
– Technology, Study design
– Genetic model
Rong Chen • Mapped to UMLS concepts
Optra Systems
8. • Study published in 2008 in
Inflammatory Bowel
Disease
• Crohn’s Disease and
Ulcerative Colitis
• Investigated 9 loci in 700
Finnish IBD patients
• We record 100+ items
– GWAS, non-GWAS papers
– Disease, Phenotype
– Population, Gender
– Alleles and Genotypes
– p-value (and confidence)
– Odds ratio (and confidence)
– Technology, Study design
– Genetic model
• Mapped to UMLS concepts
9. • Study published in
2009 in
Rheumatology
• Ankylosing
spondylitis
• Investigated 8
SNPs in IL23R in
2000 UK case-
control patients
• Tables can be rotated
• NLP is hard
10. • Study published in
2009 in
Rheumatology
• Ankylosing
spondylitis
• Investigated 8
SNPs in IL23R in
2000 UK case-
control patients
• Tables can be rotated
• NLP is hard
11. • Study published in
2009 in
Rheumatology
• Ankylosing
spondylitis
• Investigated 8
SNPs in IL23R in
2000 UK case-
control patients
• Tables can be rotated
• NLP is hard
14. Alleles for rs1004819 are C and T
~11% of records reported genotypes in the negative strand
15.
16.
17.
18. VARIMED: Variants Informing Medicine
Number of Distinct Diseases and
papers SNPs phenotypes
curated
~12,000 ~192,000 ~4,400
Chen R, Davydov EV, Sirota M, Butte AJ. Rong Chen
PLoS One. Optra Systems
2010 October: 5(10): e13574.
Personalis
19.
20.
21. Moving from OR to LR
Odds ratio
Ratio of odds of test positivity in cases over
odds of test positivity in non-cases
Likelihood ratio (+)
The probability of test positive in cases, over the
probability of test positive in non-cases
Sensitivity / (1 – Specificity)
Very similar, but different...
Morgan A, Chen R, Butte AJ. Genomic Medicine, 2010.
22. Post-test probability is calculated
with likelihood ratio
Pre-test odds x likelihood ratio Post-test odds
Pre-test odds x LR1 x LR2 x LR3 Post-test odds
Can chain likelihood ratios
from independent tests
Morgan A, Chen R, Butte AJ. Genomic Medicine, 2010.
33. Why do we even have risk alleles?
• Humans are not a very old species
• But wouldn’t we expect disease risk alleles to be
selected against?
• Disease depends on the environment
– Sickle cell trait and malaria
– Cystic fibrosis and cholera
– Lactase and milk digestion
• Some risk alleles have positive effects in the
right environment
• So when (and why) might risk alleles have
entered the human genome?
35. So what can we do about the risk?
• Diseases with higher post-test probabilities
• How to alter the influence of genetics?
• Diseases are caused by genes and environment
• We need a simple “prescription” for environmental
change for a genome-enabled patient
• How do we compensate for our genomes?
40. We already ask
physicians to
review 1 GB of
data in 15
minutes…
… but we give
them tools to help
them do this!
41. Two Major Colliding Directives in Medicine
Are Personalized Medicine and
Quality Improvement heading on Personalized
a collision course? Medicine
How are we going to treat each
patient in their own special
way, when we need to treat each
patient in a standard way?
Quality
Improvement
49. Take Home Points
• Genome-wide sequencing is here: managing
this data and relating to medicine
is the challenge.
• Personalized medicine ≥ DNA. Needs to
include diversity, and other clinical, molecular,
and environment measures.
• Teaching interns, residents, and physicians in
all disciplines will be the future rate-limiting
challenge.
50. Funded post-doctoral
positions in
Translational
Bioinformatics
available
Faculty openings for
two Assistant or
Associate
Professors
Contact Atul Butte
abutte@stanford.edu
51. Collaborators
• Jeff Wiser, Patrick Dunn, Mike Atassi / Northrop Grumman
• Ashley Xia and Quan Chen / NIAID
• Takashi Kadowaki, Momoko Horikoshi, Kazuo Hara, Hiroshi Ohtsu / U Tokyo
• Kyoko Toda, Satoru Yamada, Junichiro Irie / Kitasato Univ and Hospital
• Shiro Maeda / RIKEN
• Alejandro Sweet-Cordero, Julien Sage / Pediatric Oncology
• Mark Davis, C. Garrison Fathman / Immunology
• Russ Altman, Steve Quake / Bioengineering
• Euan Ashley, Joseph Wu, Tom Quertermous / Cardiology
• Mike Snyder, Carlos Bustamante, Anne Brunet / Genetics
• Jay Pasricha / Gastroenterology
• Rob Tibshirani, Brad Efron / Statistics
• Hannah Valantine, Kiran Khush/ Cardiology
• Ken Weinberg / Pediatric Stem Cell Therapeutics
• Mark Musen, Nigam Shah / National Center for Biomedical Ontology
• Minnie Sarwal / Nephrology
• David Miklos / Oncology
52. Support
• Lucile Packard Foundation for Children's Health
• NIH: NIAID, NLM, NIGMS, NCI; NIDDK, NHGRI, NIA, NHLBI, NCATS
• March of Dimes
• Hewlett Packard
• Howard Hughes Medical Institute
• California Institute for Regenerative Medicine
• Scleroderma Research Foundation
• Clayville Research Fund
• PhRMA Foundation Admin and Tech Staff
• Stanford Cancer Center, Bio-X • Susan Aptekar
• Rhonda Pisk
• Alex Skrenchuk
• Tarangini Deshpande
• Alan Krensky, Harvey Cohen
• Hugh O’Brodovich
• Isaac Kohane