Department of Biochemistry and Molecular Biology

George I. Mias

gmias@msu.edu

Precision Medicine Forum

G. Mias Lab

I O

gmias@msu.edu

‣ “I want the country that eliminated polio and mapped the human genome to lead a new era of medicine — one that delivers the right treatment at the right time. In some patients with cystic fibrosis, this approach has reversed a disease once thought unstoppable. Tonight, I'm launching a new Precision Medicine Initiative to bring us closer to curingdiseases like cancer and diabetes —  and to give all of us access to the personalized information we need to keep ourselves and our families healthier.” (President Barak Obama, State of the Union, 2015)

Precision Medicine Initiative

G. Mias Lab

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gmias@msu.edu

Precision Medicine‣ Complete

personalized omics

‣ integrative Personal Omics Profiling

Chen*, Mias GI*, Li-Pook-Than*, Jiang* et al Cell 148, 1293–1307 (2012)

Resource

Personal Omics ProfilingReveals Dynamic Molecularand Medical Phenotypes

Mias & Snyder, Quantitative Biology (1)1 p72 (2013)http://goo.gl/iamZth

G. Mias Lab

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gmias@msu.edu

MSH6H2AFX

RAD50

HIST2H2AB

NAP1L4

MSH3 OBFC2B

EXOSC6PDIA3PNPT1 HIST1H1ETAP2

ITSN2

TAP1

TBL3TERF1

WDR3

UTP15

DIS3

HIST1H1B

EXOSC8HIST1H4A

EXOSC9

NDUFC2NDUFS7

NDUFA2NDUFB7

NDUFB8

NDUFA3 NDUFS2NDUFA10

KRR1

CLPP

TUFM

MDH2

SLC25A11

ACO2

PMPCA

PMPCB

NDUFB6NDUFB3

NDUFS6NDUFV3

NDUFA8NDUFB9

NDUFB10

MRPS12

IDH3B

SCAND1

ATP5B

ATP5J

ATP5IATP5F1ATP5HATP5A1

CS

SLC25A4

RNF2

UQCRBUQCRC2

PCGF6

CYCS

MYST1

UQCRQCOX5A

COX6B1

ATP5G3

UQCRC1

COX5B

COX4I1

COX6C

NDUFB1NDUFB5

NDUFV1

NDUFA11

NDUFB4

NDUFA5

PCGLUD1 NAGALMNA GOT2TMPOLMNB1ATP6V1G1

PHKBGINS2GINS4

GINS1

PIGH

PIGC

ATP6V1E1PIGP ATP6V0E1

FBXO5

RNF14

C1GALT1

NUCB2SNX17

NOP2LDLR

CUL4ACUL4B

PDCD11

SPATA5

NUP37HSPD1

SNRPNHMGA1

KIN

NUP153TAF4B

RARG

NUP85

CDC5L

CORO2A

CPSF7HNRNPF

DHX9HNRNPH2SNRPESNRPG

SNRPD2HNRNPUL1

TOMM40MED28 DDX50PHAX

LSM4

NUP160

POLR2I

NUP98

TAF12 NUP35

SEH1L

NUP210

NUTF2ERH

HSPE1

CPSF1TOMM20NUP62

CPSF2 CDC40 ZRSR2

HMGN4

SMC3

DIABLOSMC4

SUMO2

TNFSF14

CENPQNSL1

CCDC99BUB1

NDEL1

UBE2V2

PPIDMED21

CENPH

CENPF

BIRC5

BCAS2

CENPN

CBX1

BANF1

NUP155PLRG1

NUP93NUP54

EFHA1

MED7

NFX1

MED31

MED4

VDAC1RCC1

ATF7

DHFR

SMARCE1CHAF1AWWOX

TP53

CDK2

TP53RKFSTLBR

BMPR1AZMAT3

SMARCC2HMGB1PARP1

PML

ERCC4

CACYBP

H3F3A

ERBB2IP

SNW1

TRIM24

UBE2E1ANAPC5

PSMB2

PTTG1

BTG1

CDC14A

ANAPC10CDC27

FBXW7

TDG

CDH2

REST

PSMC6

UBE2D1RBX1RBPJ PAWR

CAP1

SIAH1

STAG2

PRDX3

TCEB1

AURKBRAD21

CBX3

AIFM1

TRIM33

NCOA4

CUL5

ARVCFCBX5

XIAP

BUB3

PDS5APDS5B

FBLPSMA7PSMB10

ANP32EPSMA2

PSMA6PSMA1

RIF1

PHF17RANBP3

CDKN1C

GZMK

GZMA

GZMH POLB CHD9

TOB1CDK6

LEF1HMGB2

ACADM

CCNB1

POU5F1MRPL11

SCP2

LIG3

LITAF

UBE2M

MBD4

XPA

SKIL

UBE2R2HES6DDB2

DNAJA3

CCNG1

RPA3PAX5

ING2

TCF4CDKN2CTTF1

MYST4

H1FX

H1F0

DUT

SMARCD2

ACSL3

HES1

CDKN2ARUNX2

TBRG1

POLD1NOLC1

E2F3

CCND2CCNA2

PRIM2

HELLS

TOP1

FEN1

ACAA2

EBF1ECHS1

RFC1

TCEAL1

ING4RFC5

PNKP

NEURL2

COIL

MCM8DBF4

SESN1WRNIP1

HIST2H3ARRM2

NDNEI24

BCCIP

TOPORSCOPS3

KLF6

ARID2

RFWD2

YIPF5

NFKB2 RAB1A

REL

PKN2

UBE2V1

NFKBIETLR9

NKRFNFE2L2RALBP1THEM4

MAP4K3

PTPN2FYN

RTN4

HCFC1

TSC22D3

RAC1

PTPRC

INSR

MECP2TRAF3IP3

PDPK1

SIN3ACARD11

CRKMAP3K3

CCAR1PRPF6PCBP2SF3B3

PDCD7

HNRNPA3NONO

RBM17PRPF40A

TRAP1RBM42

DDX1GCC2

SRPK2

HMGN1

POLR2A

POLR2C

HNRNPCSNRPD1RANBP2 SNRPD3

UPF3ASNRNP200HNRNPDSF3B4

CSTF3PRPF4

SF3A3

SF3A1

PTBP1

SNRPB2

NHP2L1UPF3B

HNRNPL

CD2BP2NUDT21

DCP1ASNRPA1

PHF5ASF3A2

SMNDC1

TOMM70ASNRPA

HNRNPK

SRRM1

SF3B1PSIP1 RNPS1

GTF2F2

SON

UBXN4WAC

PRPF4BMATR3

JMJD1CSYNCRIP

DDX5

YTHDC1HNRNPH3

KIAA0776

WBP4

CPSF6RBM39

UPF2QKIBZW1

AHSA1TRA2A

XRN2

RB1CC1

EIF4A3

CSNK1E

PNNMETAP2BCLAF1HSP90AA1

PIF1 KTN1

RBM25PPIGARID4B

RPL6

ZNF292

ZBTB1

SEC62

NKTR

PPIL3EIF4G1

EIF4G3

SLU7

EIF1AX

HNRPLL

REEP5

GOLGA4

EIF5B

RPL10ARPL19RPL36A

EIF6

PIK3C2ARSBN1

CEP164

ARF4

CEP135SAR1B

CEP152CEP290CEP63

CENPJTUBGCP2

AKAP9

BRSK1

KLRD1

PFDN4

PPIBKLRC2

KLRC3

KIR2DS4

SLC3A2

BSG

VBP1ATP1B3

SLC16A1

KLF10

SATB1

RAB13

PA2G4

LNPEP

ARID4AIKZF4GLG1

PRNP

CYBB

PFDN2KLHL20

HCST

CYBAIL10RBCSF2RA

AGRN

PELP1IRS2

SOCS7PIK3R5

BAIAP2

MYBL1

ITGAL

RHOGIGF2R

RHOQ

KDELR1

PDK1VAMP2

AKT1S1

RHOT1

GDI2

CHD6

CD79ACD86

RUVBL2FAIM3SPTAN1CXCR4

IGJELP4

CD74LST1 SHC1

PIK3CBSOCS2

ENAHCD247

LAX1LPP

CXCR6

SPNHRH2

GNG5

ACP1

IL18

GNAS

FYB

TYROBP

DPP4

SKAP2

CALD1

GPR183PLA2G6HLA-DRB1EFNA1

PAG1GNAI2MARCKS

ADAM15

PFN2

CCL5NEK9GRAP

ING3YEATS4

MORF4L1DMAP1

TPM1

DHTKD1 OGDH

LMO4

PDPR

PDHX

PDHB

PDP2

FGD4ARHGEF18ARHGAP4ARHGAP24

ARHGAP11BG3BP2

ITSN1

CDC42EP3DLAT

ZNF321ZNF642 ZNF789

ZNF675

ZNF763ZNF22ZNF354A

ZNF100ZNF404ZFP30

ZNF737

ZNF254

ZNF564

ZNF275

ZNF20ZNF708

ZNF680

ZNF793

ZNF107ZNF493

ZNF709

ZNF714

ZNF286AZNF140

ZNF626

ZFP14

ZNF514

ZNF14

ZFP82ZNF264

RDX

ZNF345

ZNF3

SLC9A3R2

ASH2L

BAZ2B

MBD2SIGIRR

EEA1CUX1

ZNF441ZNF485ZNF324

ZNF320ZNF554

ZNF563

ZNF530ZNF91

ZNF222

ZNF268

ZNF429

BCAP31ZNF32

ZNF480

ZNF117ZNF44

ZNF43

ZNF184ZNF426

BCAP29

ZNF146

ZNF439ZNF791SNAP23

RAB3GAP2

ZNF83

VIM

PRKX

YES1FGRADD1

CDV3CNOT2PNRC2

KIF5B

SUB1

KIF5C

SUZ12

KHDRBS1CLK1NPM1

PPP2R5D

PPP2R5C

YWHAZMAP2K7 YWHABRAF1

MAP4K4 BAZ1ANCK2

MAP3K7IFI16

DDX41ETV6

FBXW11AXIN2

PSENENFOXO3

POU2F2

MYH10

CSNK1G2PPP2R2BCREB1

TLE3

HLA-DQB1NEK8 MARK3

SAP18ROCK1LCK

PRKCB

PRKY

TRIM22

NEDD9 PPARD

SP110ZNFX1IKBKAP

GYG1 BDP1SNAPC1

SPTBN1

FDXR

SQSTM1TOP2A

SSB

PEBP1NFYA

DNAJC2

TBPL1

RERE

PRF1

CAPN1RUVBL1

GYS1ADD2

POLR3AHIPK2

POU2F1

SP100

POLR3FMAPK7

GADD45A

LDHA

UBE2D3

NFIC

ME2CTCF

HSPA9

SIAH2

BAZ1B

STRADBMAF

FABP3

RAD1CAMK2D

NFATC3 RUNX3

ID2MYST2

GATA3

CTSCGTF2B

DDX46

TCERG1DEK

TBL1X

HDAC9

RBM14

TGS1

NXF1

PCNP

PDCD10IRF3

SNCA

PPARA

PTCH1

SMAD3

CORO7

MEF2CSMAD1

ZBTB44

SSR3

SEC61B

SPCS2

SRP19

SSR4SPCS3

SRPRB

SPCS1

STT3B

SRPR

SRP14

EIF5

EIF3JEIF4B

RPS28

TSGA14

DYNC1I2

FGFR1OPSDCCAG8TUBGCP4

CEP250

CETN2

TMEM126B

PABPC4

GSPT2

SEC63RPL12RPL35RPL18A

RPS15RPS15A

VAMP8

CHD4RAB27A

OFD1

RPH3AL

GATAD2B

AP1S3

integrativePersonal OmicsProfiling

I.

II.

III.

INTEGRATION OF MULTIPLE OMICS AND TEMPORAL RESPONSES MATCHED AGAINST iPOP DATABASES

iPOP Database

LONGITUDINAL OMICS PROFILING OF MULTIPLE PHYSIOLOGICAL STATESRISK EVALUATION

Transcriptomics

Whole Genome Sequencing

Medical History & Environment

Metabolomics

Proteomics

Disease Risk Evaluation

Autoantibodyomics

Microbiomics

Clinical Tests

Infected RecoveryHealthy

New omics

Healthy

Pharmacogenomic Evaluation

5 10 15

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Mias & Snyder, Quantitative Biology (1)1 p72 (2013)http://goo.gl/iamZth

G. Mias Lab

I O

gmias@msu.edu

Future Directions‣ Precision Medicine at Michigan State

• Precision Pediatrics (with Dr. Keith English)

• Maternal Infant Precision Medicine (with Dr. Richard Leach)

‣ Personalized Medicine Center for the MidWest at MSU

‣ Training of Personnel [Essential, particularly our graduate students at MSU]

‣ Core Facilities [maintain and upgrade]

‣ Clinical Involvement [Integration of Central, Grand Rapids Campuses and Beyond]

‣ Campus Partnerships for True Collaboration

‣ Responsive to Public and Funder’s Expectations for Precision Medicine Initiative by White House and NIH

G. Mias Lab

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