Overview of Personalize Medicine in the Health
System. Perspective EU & LAC countries
Iscia Lopes-Cendes, M.D., Ph.D.
Professor of Medical Genetics and Genomic
Medicine
Head, Laboratory of Molecular Genetics
School of Medical Sciences
University of Campinas – UNICAMP
Campinas, SP, BRAZIL
GENOMIC
PRECISION
Outline
• Concept and application: –Precision Medicine, Genomic Medicine and Personalized
Medicine – Examples in clinical practice (genomic tests for rare
diseases) –The importance of population genetics/genomics
• International initiatives: –Worldwide (GA4GH, ICDA) –Europe (ICPerMed and others) –Latin America (BIPMed, LatinGen)
Genomic Medicine
Identify genetic variation that causes or contributes to disease (diagnostic), informs treatment options or
patient care (therapeutic/prognostic), or provides other useful clinical information
Personalized Medicine
Precision Medicine
Current medical practice Physicians use expert background, experience and judgment to diagnose
and prescribe.
Precision medicine Use massive data network that aggregates and analyzes information from
huge patient cohorts, healthy populations, experimental organisms – and
reaches toward disease mechanisms leading to precise diagnosis and
treatment for each individual
Modified from:Yamamoto et al. 2014
Precision Medicine
Yamamoto et al. 2014
Genomic
Medicine
Personalized
Medicine
• Diverse data types in large cohorts: -omics, imaging (e.g., brain
activity, longitudinal MRI), population studies, environmental
exposures: BIG DATA
• Use of wearable sensors (biosensors): DIGITAL HEALTH
• Development of new data acquisition protocols, aggregation,
integration and analysis: DATA SCIENCE
• Challenges in data storage, security, selective access, sorting,
visualization and sharing: OPEN SCIENCE
Precision Medicine: KEY WORDS
Modified from:Yamamoto et al. 2014
2012-2015
Rare Diseases
Two genomic strategies Applied to Medicine
Finding genetic variants (SNVs) causing disease
Whole exome sequence (WES)
Clinical Genomics: Identify Clinically Relevant Genetic Variation
Discovering Disease-Causing Genetic Variants (WES)
100,000 genetic variants
10,000 associated with protein-coding genes
5,000 possibly of disease causing
type
1500 <1% frequency in population
One clinically Relevant
Genetic Variant
Genomic tests: knowledge required
Variant
Gene
Population Frequency
Pathways
Functions
Tissues
Variant Type
Impact on Protein
Phenotype
Population context of a variant
Population Genomics
Human genetic variation.Proportion of shared and unshared (private) variants between the African-American and the European-American populations [data from (1)].
Ferran Casals, and Jaume Bertranpetit Science 2012;337:39-40
Published by AAAS
Rare Disorders
BIPMed - Brazilian Initiative on Precision Medicine
www.bipmed.org
SAVE THE DATE
The São Paulo Research Foundation, FAPESP, under the scope of the program Research, Innovation and Dissemination Centers (RIDCs), invite you to the
Launching of the
BRAZILIAN INITIATIVE ON PRECISION MEDICINE
BIPMed November, 13, 2015
1:30pm to 5:00pm
Venue: FAPESP - Rua Pio XI, 1500
Alto da Lapa – São Paulo
BIPMed is an initiative of five Research Innovation and Dissemination Centers (RIDCs): The Brazilian Research Institute for Neuroscience and Neurotechnology (BRAINN), Center for
Computational Science and Engineering (CCES); Center for Research in Cell Therapy (CTC); Obesity and Comorbidities Research Center (OCRC); and Center for Research on Inflammatory
Diseases (CRID).
Precision Medicine has emerged recently as a concept in which scientific knowledge and technology will come together to provide the bases for the 21st century medicine. It embraces
translational research, genomic medicine and personalized medicine and proposes a new level of integration of data in order to improve health care.
BIPMed will be based initially on a software platform, built following the guidelines and principles of the Global Alliance f or Genomics and Health (http://genomicsandhealth.org/), and
observing the responsible sharing of genomic and clinical data. This platform will be the first of its kind in Latin America. It is intended to be used by clinicians and scientists all over
the world, to share and obtain information about various aspects of genomic medicine and human health, as well as to support dissemination and training.
Preliminary program
1:30 PM – 1:40 PM Registration
1:40 PM – 1:50 PM Welcome and introduction – FAPESP and
Members of BIPMed
1:50 PM – 2:40 PM Importance of BIPMed in the context of RIDCs
2:40 PM – 3:00 PM Importance of BIPMed in the context of
FAPESP
3:00 PM – 3:45 PM BIPMed in the international context:
Representative(s) of the GA4GH
3:45 PM – 4:00 PM Q&A, followed by official on line launching
4:00 PM – 4:45 PM Refreshments
For more information, click here.
IMPORTANT INFORMATION:
To receive more information about the event, such as the list of confirmed speakers and program, please fill the preliminary form indicating your interest, available at:
www.fapesp.br/eventos/tap/interest
Filling out this form does not guarantee your registration for the event. The registration form will be available only in Oct ober for those who filled the preliminary form.
Official language: English
(Simultaneous translation will not be provided)
Mission
• To help implement precision medicine in Brazil by acting as a catalytic element to foster collaboration among different stake holders (scientist, physicians, health authorities, hospitals, society)
First product: BIPMed genomic database
Global Alliance for Genomics & Health
Databases
BIPMed
• Gene table
www.bipmed.org
Mission
To accelerate progress in human health by helping to establish a common framework of harmonized approaches to enable effective and responsible sharing of genomic and clinical data, and by catalyzing data sharing projects that drive and demonstrate the value of data sharing
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Developing documents, products and supporting projects aiming to foster data-sharing
2014
Framework for Responsible Sharing of Genomic and Health-Related Data
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The Framework is currently available in 12 languages. Thank you to all the volunteers!
• Arabic
• Chinese
• French
• Greek
• Japanese
• Portuguese
• Spanish
• German
• Hindi
Πλαίσιο για την Υπεύθυνη Κοινοχρησία Γονιδιωματικών και άλλων
Ιατρικών Δεδομένων
基因组学与健康相关数据负责任的共享框架
إطار لتبادل مسؤول للمعلومات الجینومیة والمتصلة بالصحة
Cadre pour un partage responsable des données génomiques et des données de
santé
ゲノム及び健康関連データの責任ある共有に関する枠組み
Marco de actuación para el uso compartido responsable de datos
genómicos y relativos a la salud
Framework para Compartilhamento Responsável de Dados Genômicos e
Relacionados à Saúde
Rahmenkonzept für die verantwortungsvolle Datenweitergabe genomischer
und gesundheitsbezogener Daten
Demonstration Projects – Knowledge Exchanges
The Beacon Project is an open web service that tests the willingness of international sites to share genetic data. It is being implemented on the websites of the world's top genomic research organizations.
Matchmaker Exchange is a federated network of databases whose goal is to find genetic causes of rare diseases by matching similar phenotypic and genotypic profiles.
The BRCA Exchange (Challenge) aims to advance understanding of the genetic basis of breast cancer and other cancers by pooling data on BRCA genetic variants from around the world, bringing together information on sequence variation, phenotype and scientific evidence. Improved understanding of genetic variation in these genes has the potential to improve patient diagnoses and prevention of disease.
An emerging initiative in Somatic Cancer proposes to aggregate somatic cancer mutation data and some clinical data in order to improve the genomic landscape of actionability in some cancers and to enable greater personalized clinical care for individuals with rare cancer mutations.
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Beacon Project
Cancer Gene Trust
BEACON
https://beacon-network.org
BIPMed
National Initiatives
Data Sharing
www.bipmed.org
Informed consent
Level 1 or Unrestricted Access: This is the standard access level and it does not require user registration or authentication. Users can access polled statistics, list of variants; frequency. Users do not have access to individualized data.
Level 2 or Restricted Access: It requires registration and users can request access to files containing specific datasets. Registered users must sign a Data Sharing Agreement, which includes a confidentiality clause. Registered users can request Individual VCF files containing variants information.
LEVELS OF ACCESS OF GENOMIC INFORMATION DEPOSITED IN THE BIPMED
PUBLIC GENOMIC DATABASE
BIPMed
Our Products:
•Genomic databases (898 individuals):
•BIPMed-WES-db: REFERENCE POPULATION
•BIPMed-Array-db: REFERENCE POPULATION
•DISEASE SPECIFIC DATABASES: customized (9)
Disease/Phenotype specific projects
- Epilepsy (BRAINN, ILAE-ALADE) - EE
- Stroke (BRAINN, ISGC) – Dr. Norberto Cabral
- Cleft lip and palate (BCFP) – Dr. Vera Lopes
- BRCA – BRCA Challenge (GA4GH, HVP) – Dr. Patricia Prolla and Dr. Edenir Palmero
- Pathogenic hemoglobins – Global Globin (HVP) – Dr. Monica Melo
- ApoE Challenge – Dr. Marcio Balthazar
- Pharmacogenomics (PharmVar) – Dr. Marcelo Briones
- Hereditary Spastic Paraplegias – Dr. Jonas Saute and Marcondes França Jr.
- ….
BIPMed-WES-db
14.8 % Filter variants without dbSNP ID
Variants covered in more than 50% of
samples
ASW
BRA
JPT+CHB+CHD
CEU
MKK
LWK
YRI
TSI
MEX
BIPMed SNP-arrays 196 individuals
Asia
Americas
Africa
Europe
HapMap
x
Gráfico de Componentes Principais: PC1 x PC2 x PC3 Recife, PE Campinas, SP Joinville,SP
Ananina G
submitted
Fine scale
genetic
structure of the
populations
from three
Brazilian
regions
Genome-wide ancestral haplotypes
• Comparing two individuals
Global
ancestry
Global
ancestry
ID1 ID2
BIPMed data: local ancestry inference
Secolin et al., Scientific Reports 2019
80%
12% 8%
Latin American Database of Genetic Variation (LatinGen)
Supported by RELAGH:
Rede Latino Americana de Genética Humana Red Latino Americana de Genetica Humana
ELAG – May 12, 2017
www.latingen.org
LatinGen
• AIM: To support data-sharing in Latin America by fostering collaboration and integration among projects in different countries:
- To facilitate integration between public databases already stablished in LA
- To stimulate and support new initiatives by providing technical assistance (bioinformatics expertise) to implement and to integrate public databases in LA
LatinGen
LatinGen: www.latingen.org
Questions for research projects:
i) Propose a research project to evaluate the power of
admixed populations to better understand the role
of modifier genes in complex diseases.
ii) Propose a search project that, in addition to answer
a specific research question, could also create
infra-structure to enable the application of
genomic medicine.
-
Conclusions
• Change in paradigm in Medicine
• Genomic Medicine is already a reality; however, to achieve Precision Medicine we need a higher level of integration of information from different sources. Sharing population level data
• Latin America is part of this global process with the launching of BIPMed and LatinGen, which is integrated with international initiatives
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Genetic Testing: important recommendation
• No genetic test should be ordered without the patient informed consent. Since genetic information can be complex, it is important to make sure the patient understands the ramifications of testing in order to make an informed choice.
visit us at
www.bipmed.org
and
www.latingen.org