Theodosius Dobzhansky Center for Genome Bioinformatics

May 25, 2015 St. Petersburg State University

Founded 1724

"Nothing in Biology makes any sense except in light of evolution" Theodosius Dobzhansky

Genomic Medicine

GWATCH - A new frontier in Genome Wide Association Analyses

and Data Release

• GWAS

GWAS

GWATCH A suite of genome tools and programs to discover, view and assess hits from GWAS and WGS

• Genome • Wide

• Association • Tracks

• Chromosome • Highway

Display Everything beyond Manhattan

GWATCH Snapshots-

2D 3D

2D Snapshot -Chromosome 7 CFTR Region

SNPs

Tests

A heat plot of p-values for 131 ARG association tests 200+ SNPs in each region ~26,000 SNP-test com in

Genetic association Tests

PROX1 region chr 1

PROX1 2D Snapsho

PROX1 polarized

Promise of GWATCH • Automate analyses of GWAS and WGS • Improve display

• Instant replication of hits without Bonferroni pena

• Open data release without violating patient privacy

•Let’s take a ride along a chromosome

GWATCH

Genetic Diversity of the Russian Mycobacterium

tuberculosis strains GMTV Database

Ekaterina Chernyaeva

St. Petersburg State University

11.06.2015 19

MTBC History

• MTBC emerged about 70,000 years ago, accompanied migrations of anatomically modern humans out of Africa and expanded as a consequence of increases in human population density during the Neolithic period

11.06.2015 20

M. tuberculosis H37Rv genome

SIZE: 4411532 b.p. GENES: 3993 protein coding 50 RNA coding GC CONTENT: 65% INSERTION ELEMENTS: 56 copies of IS-elements (Families IS3, IS5, IS21, IS30, IS110, IS256, ISL3, IS1535)

MTBC genetic diversity

• MTBC is characterized by 99.9% similarity of 16S rRNA gene, but differ widely in terms of their host tropisms, phenotypes and pathogenicity

• 14 “Regions of Difference” which discriminate all MTBC members

11.06.2015

GMTV Database Genome-wide Mycobacterium tuberculosis Variation Database http://mtb.dobzhanskycenter.ru Includes 1084 M. tuberculosis genomes collected across Russia over 69,000 SNP or Indel variants Drug resistance information Clinical Data (diagnosis, HIV-status) Geographical information Gender Year of isolation

11.06.2015 22

TB Centers of surveillance

Countries

UK, USA, China, Canada, Portugal, Germany, Georgia, Uzbekistan, Netherlands, Malawi, Uganda, South Africa, Global collection (Ethiopia, Vietnam, Mexico, South Korea, Pakistan, Senegal, Cambodia, Gambia, Malaysia, Sri Lanka, Nepal, India, Ghana, Sierra Leone, Tanzania, Iran, Afghanistan, Turkey, Singapore, Burkina Faso, Turkmenistan, Colombia, Puerto Rico, Nicaragua, Mongolia, Indonesia, Thailand, Burma, Laos, The Philippines, Guatemala, Salvador, Somalia)

11.06.2015 24

Clinical Data in GMTV

• HIV-status: - 11 isolates revealed from HIV-infected patients - 19 from HIV-negative • Clinical outcome: - 12 patients with extrapulmonary TB - 15 patients with pulmonary TB - 3 patients with pulmonary and extrapulmonary localizations. • Drug resistance: - 478 multiple drug resistance (MDR) - 60 Extensive Drug Resistance (XDR)

11.06.2015 25

Comparative Genomics

10,000 vertebrate genomes

Sequencing 10,000 Vertebrate Species

Of circa 60,000 species • 3000 of 5,000 mammals • 2000 of 10,000 birds • 1300 of 8,500 reptiles • 700 of 6,500 amphibians • 3000 of 30,000 fish

Coming Now

Role of G10K Community of Scientists

• Gather Voucher specimens • Identify species’ biological communities • Set Standards for Genome:

– Assembly – Annotation – Release on Browser

• Monitor progress • Rapid data release • Raise funds • Spawn Offspring…..

Felidae Genome Consortium

20,343

O'Brien, S. J. , Wildt, D. E. , Goldman, D. , Merril, C. R. , and Bush, M. :

The Cheetah genome-Statistics • Namibian Cheetah Chewbacca-75X coverage

Illumina HiSeq BGI • Six cheetahs seqiuenced ~6x coverage

– Tanzania -3 - A. jubatis rainei – Namibia -3 -A. jubatis jubatis – 8 mate pair libraries

• N50 – Contigs 28.2 kbp – Scaffolds 3.1Mbp

• Estimated genome size – 25x raw reads 2.395 GBP – Assembly 2.375 Gbp

• Assembly • SOAP denovo • Assisted assembly with FCA 6.0

– RH map 3000 markers – SNP array LM 60,000 markers

SNV frequency in different Mammal genomes

0

0,0005

0,001

0,0015

0,002

0,0025

Feline Genome Project

May 25 2015 FELIDAE GENOMES sequenced or promised

Species genome sequence Where done Publication status plans

Common name

Felis catus Domestic cat Wash U GigaScience 2014;PNAS 2014;Gen Res 2009

Felis silvestris Wildcat NIAAA Analysis

Acinonyx jubatus Cheetah BGI Submitted

Panthera leo Lion Korea Nature Comm 2014

Panthera leo Af & Asian lion BGI Writing up now

Panthera tigris Tiger Korea Nature Comm 2014

Panthera uncia Snow Leopard Korea Nature Comm 2014

Panthera pardus Leopard Hudson Alpha; Moleculo Illumina Just started

Panthera onca Jaguar Univ Porte Allegra Analyses

Lynx pardalis Iberian Lynx Spain Writing up now

Puma concolor Florida panther & BGI Just started

Puma concolor Western Puma UCSC Just started

Neofelis nebulosa Clouded leopard Smithsonian gatherring samples

Neofelis diardi Sunda Cl.Leopard Smithsonian gatherring samples

Prionailuris bengalensis Leopard cat Natural History Museum of Denmark, gatherring samples

Prionailuris viverrina Fishing cat Natural History Museum of Denmark, gatherring samples

Caracal caracal caracal Natural History Museum of Denmark, gatherring samples

Prionailuris rubiginosis Rusty Spotted cat Natural History Museum of Denmark, gatherring samples

Crocuta crocuta Hyena BGI Pending; read done at BGI

Canis familiaris dog Broad Nature

Manis pentadactyla Chinese pangolin Wash U analyses

Manis javanica Malayan pangolin u Malaysia Analyses

Conservation Genetics

Shujin Luo & Jae-Haup Kim

G10K Offspring 1000 fungal genomes

Highlights of Dobzhansky Center 2012-2015 • Center staffed to ~30 employees and occupied labs on

Sredniy Prospekt Oct. 2012 • Hosted 6 lab retreats and 30+ science visitors; chaired 6

Conferences • Hosted international web sites. • Led and coordinated Genome10K project • Published > 140 peer reviewed papers in high ranking

journals • Initiated Genome Russia Project 2015-2-2018 • Education in courses, Coursera Online, ConGen and G10K. • Accessed and housed sequence and genotypes data from 30

species genomes and 12,000 human study participants in disease gene association studies

1000 genomes

Studies of human genomic variation have great potential to identif genes that may underlie differences in disease resistance (e.g., MHC region) or drug metabolism

Цели и задачи: Genome Russia Mission

• 1. Создать биоибанк тканей и ДНК представителей крупных

этнических групп, живущих в России. • 2. Составить каталог геномных вариаций в рамках этнических

групп. • 3. Документированное описание структуры и распределения

генов различных заболеваний, наследуемых • населением России • 4. Созадать Русский HapMap - проект, который поможет

исследователям найти гены, связанные с заболеванием • человека и ответ на лекарственные препараты. • 5. Вычленение у характреситика специфических изменений

геномной ДНК, характерных лишь для населения России. • 6. Изучить пути древних географических перемещений предков

современных русских народов. • 7. Разработать инновационные биоинформатические

алгоритмы и подходы, применимые к анализы болезней, вызванных охарактеризованными в ходе проекта генов

Международный проект HapMap - партнерство ученых и финансирующих учреждений Канады, Китая, Японии, Нигерии, Соединенного Королевства и Соединенных Штатах Америки по разработке общественного ресурса, который поможет исследователям найти гены, связанные с заболеванием человека и ответ на лекарственные препараты.

Русский проект внесет свою лепту в международные усилия, сконцентрировавшись на особенностях и разнобразии российского населения Russian HapMap

Genome Russia Concortium

21 groups from 14 cities

1000 RU Genomes

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And now I really would like to say "Thanks" to…

GWATCH

Russian Mycobacterium tuberculosis GMTV Database

Theodosius Dobzhansky Center for Genome Bioinformatics

St. Petersburg

St. Petersburg State UniversFounded 1724

Dobzhansky Center Excited author in the process of research.