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

icendes@unicamp.br

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)

UNICAMP

USP

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

We are hiring

icendes@unicamp.br

Thank you