Genomics, Omics, and the Future of Space Travel

1 Daniela Bezdan, NASA 2017

Genomics, Omics, and the

Future of Space Travel

Daniela Bezdan

Weill Cornell Medicine

Department of Physiology and Biophysics &

The Institute for Computational Biomedicine,

April 11, 2017

Photograph by: Astronaut Scott Kelly

@mason_lab


DNA RNA Proteintranscription translation

ONCE UPON A TIME…


Epigenome Epitranscriptome Epiproteome (PTM)


RT

ACGT

viRNA prions

iDNA

mC,hmC, 8oxoG, m6A

(sn/sno/g)RNA (t/r/tm)RNA

(lnc/nc/mi/piwi/si/vi)RNA

scRNA

RbP

Ribozymes Prions

iRNA iProtein

mC,hmC, 8oxoG, m6A, … m6A, 5’G,polyA, … Acet, Phos, Citr, SUMO, …

Saletore et al., Genome Biology, 2012

…MORE ACCUARATE PICTURE


THE OTHER LAYER…


THE OTHER LAYER…

DNA level


THE OTHER LAYER…

DNA level




RT

ACGT

viRNA prions

iDNA

mC,hmC, 8oxoG, m6A



scRNA

RbP

Ribozymes Prions

iRNA iProtein



…CURRENT PICTURE




RT

ACGT

viRNA prions

iDNA

mC,hmC, 8oxoG, m6A



scRNA

RbP

Ribozymes Prions

iRNA iProtein



DNA & EPIGENOME

9 Daniela Bezdan, NASA 2017The Encode Project Consortium, Nature, 2012

MOSAICISM – MODIFICATION OVER TIME

Wang Y et al. Maternal mosaicism is a significant contributor to discordant sex chromosomal aneuploidies associated with noninvasive prenatal testing. Clinical Chemistry 2014; 60(1):251-9.

% o

f ce

lls w

ith

X

Ch

rom

oso

me

Loss

(XC

L)


The Encode Project Consortium, Nature, 2012

TELOMERES


CHASING THE LONGEST READ TO GET TELMERES…

50.000bp


Mario F. Fraga et al. PNAS 2005;102:10604-10609

GENOMICS OVER TIME - EPIGENETIC DRIFT IN TWINS


EPIGENETIC DRIFT IN TWINS – TWIN STUDY




RT

ACGT

viRNA prions

iDNA

mC,hmC, 8oxoG, m6A



scRNA

RbP

Ribozymes Prions

iRNA iProtein



EPITRANSCRIPTOME


Meyer et al., Cell, 2012.Saletore, Chen-Kiang, and Mason, RNA Biology, 2013.

MANY ROLES FOR RNA MODIFICATIONS


Saletore et al., “The Birth of the Epitranscriptome.” Genome Biology, 2012.

RNA MODIFICATIONS SPANS THE KINGDOM OF LIFE




RT

ACGT

viRNA prions

iDNA

mC,hmC, 8oxoG, m6A



scRNA

RbP

Ribozymes Prions

iRNA iProtein



MORE LAYERS?


UNDERSTANDING NETWORKS


LAYERS DEFINES THE TERM “OMICS”


OMICS NOT ONLY IN ONE SPECIES…

….HOW ACTUALLY COMMUNITIES HAS AN INFLUENCE

TO EACH OTHER?….

METAGENOMICS!


NEW EXTREME SAMPLING SITES SITES

www.extrememicrobiome.org


http://metasub.org/

MetaSUB


NEW EXTREME SAMPLING SITES SITES – SPACE!

www.extrememicrobiome.org


SAMPLING IN SPACE


SAMPLING IN SPACE

http://www.youtube.com/watch?v=VmhEtPN5u9YAstronaut Koichi Wakata

http://www.youtube.com/watch?v=VmhEtPN5u9Y


http://www.youtube.com/watch?v=0ODYdyLy9Tg

Traditional – sampling and transport


CELLS WITHIN 36H AFTER BEING IN THE ORBIT

Plasma

PBMCs

Ficollplug

http://www.nature.com/nprot/journal/v9/n7/fig_tab/nprot.2014.104_F5.html


MAYBE WE CAN DO BETTER THEN THAT…

MAYBE WE ARE ABLE TO SEQUENCE THE SAMPLES

ON SITE!


MINION MAKE IT POSSIBILE – OXFORD NANOPORE


SPACE MOLECULE SEQUENCER PROJECT IS BORN…

http://www.nasa.gov/mission_pages/station/research/experiments/2181.html


KATE IS TAKING A LEAD


PREPERATION AND TRAINGING…


SpaceX CRS-9: perfect launch and booster returnJuly 18, 2016

LAUNCH!


SUCCESS


WHAT WE CAN DO MORE WITH THE DATA?




RT

ACGT

viRNA prions

iDNA

mC,hmC, 8oxoG, m6A



scRNA

RbP

Ribozymes Prions

iRNA iProtein



DIRECT SEQUENCING OF BASE MODIFICATIONS


Calling current (pA) differences for epigenomics in space



Random forest model for Oxford Nanopore base modification sequencing:

So far ~88% accurate



TEAM WORK


Thanks to Funding from: @mason_lab


Illumina

Gary Schroth

Marc Van Oene

Univ. Chicago

Yoav GiladFDA/SEQC/Fudan Univ.

Leming Shi

NIH/UDP/NCBI

Jean & Danielle Thierry-Mieg

Baylor

Jeff Rogers

MSKCC

Danwei Huangfu

Christina Leslie

Ross Levine

Alex Kentsis

HudsonAlpha

Shawn Levy

Mason Lab

Christopher Mason

Ebrahim Afshinnekoo

Sofia Ahsanuddin

Noah Alexander

Pradeep Ambrose

Daniela Bezdan

Marjan Bozinoski

Dhruva Chandramohan

Chou Chou

Tim Donahoe

Francine Garrett-Bakelman

Jonathan Foox

Elizabeth Hénaff

Alexa McIntyre

Cem Meyden

Niamh O’Hara

Lenore Pipes

Jake Reed

Darryl Reeves

Heba Shabaan

Priyanka Vijay

David Westfall

Cornell/WCM

Scott Blanchard

Selina Chen-Kiang

Olivier Elemento

Samie Jaffrey

Ari Melnick

Margaret Ross

Epigenomics Core

Duke

Stacy Horner

Nandan Gokhale

Icahn/MSSM

Eric Schadt,

Andrew Kasarskis,

Joel Dudley, Ali

Bashir,

Bobby Sebra

ABRF

George Grills

Scott Tighe

Don Baldwin

Miami

Maria E Figueroa

AMNH

George Amato

Mark Sidall

@mason_lab

NYU

Martin Blaser

Jane Carlton

Julia Maritz

Chris Park

MIT Media Lab

Kevin Slavin

Devora Najjar

Regina Flores

Rockefeller

Jeanne Garbarino

Charles Rice

NASA

Aaron Burton

Sarah Castro-Wallace

Kate Rubins

Graham Scott

Craig Kundrot

Jackson Labs

Sheng Li

THX!


NGS – PacBio & 10X genomics


NGS platforms – Illumina

MiSeq HiSeq NovaSeq

ProjectFirefly

NextSeq


DNA preparation protocols – making a library

Bar-Seq

mutARS-Seq TraDI-Seq

Ig-Seq Tn-Seq BS-Seq

WIMP-Seq Ig-seq IN-Seq BisChIP-Seq

BOINC-Seq Ren-Seq Immuno-Seq Phenotyping

dsRNA-Seq Nucleo-Seq Repli-Seq Cel-Seq PAS-Seq PDZ-Seq

FRAG-Seq DNAse-Seq ARS-Seq 3P-Seq PAL-Seq PD-Seq

CLASH-Seq SHAPE-Seq DNAseI-Seq Sort-Seq NET-Seq Translation Chem-Seq

RNA-DNA binding PARTE-Seq Sono-Seq Pool-Seq SS3-Seq Ribo-Seq SELEX-Seq

ChIRP-Seq PARS-Seq Hi-C-Seq Replication FRT-Seq Frac-Seq CRE-Seq

CHART-Seq Structure-Seq ChIA-PET-Seq Bubble-Seq 3-Seq GTI-Seq STARR-Seq

RAP-Seq DMS-Seq FAIRE-Seq Transcription PRO-Seq RIP-Seq SRE-Seq

Mu-Seq Viral RNA NOMe-Seq RNA-Seq Bru-Seq PAR-Clip-Seq HITS-KIN-Seq

Stable-Seq Cir-Seq ATAC-Seq GRO-Seq TIF-Seq iCLIP-Seq Capture-C-Seq

DNA RAD-Seq Quartz-Seq 3′-Seq PTB-Seq

Dup-Seq Freq-Seq CAGE-Seq TIVA-Seq ChIP-Seq

IMS-MDA-Seq CNV-Seq Nascent-Seq Smart-Seq ChIP-Seq

Novel-Seq fCAB-Seq CAB-Seq HiTS-Flip-Seq

TAm-Seq MeDIP-Seq HELP-Seq Chip-exo-Seq

Methyl-Seq TAB-Seq PB-Seq

oxBS-Seq TAmC-Seq AHT-ChIP-Seq

RBBS-Seq

Genomics, Omics, and the Future of Space Travel

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