국민의료진단시스템개발의미래 BioBank 인체자원은행 …

국민의료진단시스템개발의미래:BioBank (인체자원은행) Big+Data+와 AI+의융합

K.+Hun+Mok++(睦憲),+Ph.D.+Trinity+College+DublinTrinity)Biomedical)Sciences)Institute)(TBSI)School)of)Biochemistry)and)ImmunologyProtein)Folding)and)Biomolecular)NMR)Spectroscopy)Lab)/)TBSI)NMR)FacilityDublin)2,)Ireland

17th September+2021+(Fri)

<제 9차> 바이오헬스

2021년글로벌신산업J신기술세미나Online)Symposium,글로벌기술협력지원단 (KGTAG)한국산업기술진흥원 KIAT

AcknowledgementsLouise'M.'Sullivan''''''''Níal P.'Harte''''''''''''''Yongjing Xie

Pancham S.'Kandiyal Anna'Hastings''''''''''Ji'Yoon'Kim''''''''Daniel'L.'FortunatiSoyoung'Min''''''Yeon'Joong'Yong''''''''''Ki Hyung Kim''''''''''''''Sohyun'Kim

Catharina'Svanborg (Lund'University,'Sweden)'''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''André'Brodkorb (Teagasc'Food'Research'Centre,'Moorepark)Michael'J'Rowan (Trinity'College'Dublin)John'J'Boland'''''' (Trinity'College'Dublin)Kyou Hoon Han''''''''''''''''''(KRIBB,'Korea'Research'Inst'of'Biosci and'Biotech)Eun Kyu Lee'''''''''''' (Hanyang'University,'Ansan,'Korea)

Funding:'''FIRM'(DAFM),'Enterprise'Ireland'(Rep'of'Ireland)''/Swedish'Research'Council''(Sweden)'''/''''''BBSRC'(UK)'

Lee/Sherlock///////////Brendan/Martin//////////////Sinha/Behsanger

Table&1.&Basic&characteristics&of&KarMeN&study&participants.

Rist%MJ,%Roth%A,%Frommherz%L,%Weinert%CH,%Krüger%R,%et%al.%(2017)%Metabolite%patterns%predicting%sex%and%age%in%participants%of%the%Karlsruhe%Metabolomics%and%Nutrition%(KarMeN)%study.%PLOS%ONE%12(8):%e0183228.%https://doi.org/10.1371/journal.pone.0183228https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183228 인체

자원은행

(Bioban

k)*의

축소형예

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183228

Fig$1.$Metabolite$patterns$for$the$prediction$of$sex.

Rist%MJ,%Roth%A,%Frommherz%L,%Weinert%CH,%Krüger%R,%et%al.%(2017)%Metabolite%patterns%predicting%sex%and%age%in%participants%of%the%Karlsruhe%Metabolomics%and%Nutrition%(KarMeN)%study.%PLOS%ONE%12(8):%e0183228.%https://doi.org/10.1371/journal.pone.0183228https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183228

Plasma Urine

Male$ Female Male$ Female


Table&2.&Prediction&accuracy&of&sex&of&the&KarMeN&study&participants&based&on&metabolite&profiles&in&plasma&and&urine&using&different&algorithms.



Fig$2.$Metabolite$patterns$for$the$prediction$of$age$in$men.


Plasma Urine

Younger$ Older Younger$ Older


Table&3.&Prediction&of&chronological&age&of&the&KarMeN&study&participants&based&on&metabolite&profiles&in&plasma&and&urine&using&different&algorithms.


S2 Fig.: Concentrations of selected metabolites contained in metabolite patterns

important for prediction of age in male study participants versus age. Plots are

shown for (A) plasma and (B) urine metabolites of male study participants with mean rank

1 (left panel) and 25 (right panel). PO4, phosphate; U2.50, unknown NMR analyte at 2.5

ppm; 4-HMA, 4-hydroxymandelic acid; a.u., arbitrary units.

Urine

Plasma


대사체학 Metabolomics

시스템생물학Systems'Biology

Metabolomics

Metabonomics

Integration*of*genomic,*transcriptomic,*proteomic,*etc*data*to*understand*function*through*different*levels*of*biomolecular*

organization.

Measurement*of*metabolite*fluxes*and/or*secretionsin*cells*and*tissues.

Measurement*of*multivariate*metabolic*responses*due*to*pathophysiological*stimuli*or*genetic*modification.

TRACT'NMR'Metabolomics'Training KH'Mok

U P SmSa Se WBBS C5"Hydroxyindoleacetic0acid Intestinal0Carcinoid0syndrome0 LCMSAcylcarnitines0 Fatty0acid0oxidation0disorders,0several0organic0acidurias0and0new0born0screening0 ESI"MSAcylglycines0 Inborn0errors0of0metabolism0 Capillary0GCMSAllo"isoleucine New0born0screening:0branched0chain0amino0acids0elevations0 LCMSAmino0acid0(Panel) Inborn0errors0of0metabolism:0ovaluation0of0endocrine0and0neurological0disorders,0liver,0muscle0&0neoplastic0diseases0 LCMSAminolevulinic0acid Various0acute0hepatic0porphyrias0 LCMSBile0acid0 Liver0dysfunction Enzymatic0&LCMSCarnitines0 Organic0acidemias,0fatty0acid0oxidation0disorders0and0primary0carnitine0deficiency0 MScarotene"0beta Fat0Malabsorption0 HPLCCeramides Myocardial0infarction,0cardiovascular0disease0and0mortality0within050years0 LCMSCholesterol0 Evaluation0of0cardiovascular0risk0 Enzymatic0&LCMSCitric0acid Metabolic0disease0 Enzymatic0SpectrophotometryCortisol0 Cushing0syndrome0&0adrenal0insufficiency0 LCMS0&Immunoenzymatic0AssaysCeatine0 Renal0function0 Enzymatic0d"lactate0 d"lactate0acidosis0 EnzymaticEthylmalonic0acid New0born0screening0 LCMSFatty0acid0profiles0 Identifying0deficiency0of0essential0and0other0nutritionally0beneficial0fatty0acids0 Capillary0GCMSFructosamine0 Glyceamic0control0 ColourmetricFructose Azoospermia0 Qualitative0Test0Galactitol0 Galactosemia0 GCMSGlucose Diabetes0&0carbohydrate0metanolism0disorders0 Photometric0Glutaric0acid0 New0born0screening0 LCMSHDL0cholesterol0 Cardiovascular0risk0 Colourmetric0&0EnzymaticHippuric0acid Liver0function0 LCMSHistamine0 Allergies0and0mast0cell0disorders0 Immunoenzymatic0Assays0Homocysteine Inherited0disorders0of0methionine0metabolism0 ESI"MSHomovanillic0acid0 Screening0children0for0catecholamine"0secretig0tumours0 LCMSHydroxyglutaric0acid0 New0born0screenings LCMSInsulin Insulinoma0 Electrochemiluminescence0Immunoassyas0Lactate0 Lactic0acidosis0&0differentiating0between0bacterial0and0viral0meningitis0 Photometric0LDL0Cholesterol0 Cardiovascular0risk0 Colourmetric0&0EnzymaticMethylmalonic0acid0 Methylmalonic0acidemia0 LCMSMethylsuccinic0acid New0born0screenings0 LCMSOrganic0acid0screen0 Inborn0erros0of0metabolsim0 GCMSphenylalanine0and0tyrosine0 Hyperphenylalaninemia MSPhospholipids0 Lecithin"cholesterol0acyltransferase0deficiency0 ColourmetricPipecolic0acid Peroxisomal0biogenesis GCMSPurines0and0pyramidines0(panel) Disorders0of0purine0and0pyrimidine0metabolism0 LCMSPyridoxal05"phosphate Progressive0nerve0compression0disorders0 LCMSPyruvate0 Disorders0of0mitochondrial0metabolism0 Spectroscopy0Riboflavin0vitamin0B20 Ariboflavinosis0 LCMSThiamine0 Behavoural0change,0delerium,0dietry0concerns0 LCMSTriglycerides0 Elevated0cholesterol0values0 EnzymaticUrea0 Renal0failure0 UVUric0acid0 Acute0uric0acid0nephropathy0from0other0causes0of0acute0renal0failure0 Enzymatic0&Photometric0

Biological/Matrix/

Analytical/Test/Clinical/Relevance/Biomarker/

Clinically(useful(biomarkers.(U:#urine,#P:#plasma,#Sm:#saliva,#WB:#whole#blood,#BS:##dried#blood#spot,C:#CSF#(cerebrospinal#fluid).

Originally#sourced#from#the#Mayo#Clinic,#US.[Ref:#D.#K.#Trivedi,#K.#A.#Hollywood,#and#R.#Goodacre,#New$Horiz Transl Med,$vol.#3:#294Q305,#2017. ]

Metabolomics, Relatively,Large,Data,Sets,(1)

305,214,da

ta,points

Metabolomics Relatively/Large/Data/Sets/(2)

32,700/rows/x/143/subjects

MetabolomicsVisualizing*metabolic*space*and*influence*vectors�Principal*Components*Analysis*(PCA)�

TRACT%NMR%Metabolomics%Training KH%Mok

다변량분석Multivariate/Analysis

Mok$KH$group$expertise:$$$Instrumentation

The$NMR$Facility$at$Trinity

High%resolution.NMR.capacity.realises:

% Novel&drug&development&(“SAR%by%NMR”)% The&validation&of&molecular&identity(biosimilars /&protein&aggregation)

% Metabolomics of&cells,&serum,&urine&–Large?scale&biobank profiling

% Atomic?level&3D&biomolecular&structure&&&&&% Structure&elucidation&of&nano?scale&/inorganic&materials

! Currently*the*highest*magnetic*field*in*all*of*Ireland*and*NI.

! Equipped*with*1H/15N/13C*cold*(cryo)*probe,*biomolecular*solid*state*MAS*probes,*triple*axial*pulsed!field*gradient*probes,*etc.

! With*the*cold*probe,*capabilities*of*detecting$metabolites$and$in#vivo#sample$concentrations$of$sub@μmolar range.

What%is%NMR?% High%resolution, atomic%level methodology forthe determination of chemical and biochemicalstructures of molecules.% Proteins, nucleic acids, sugars, lipids, drugs

The%principleof%NMR%isidentical%to:

Mok$KH$group$expertise:$$$Instrumentation

The$NMR$Facility$at$TCD$$$(800$MHz)

High%resolution.NMR.capacity.realises:

% Novel&drug&development&(“SAR%by%NMR”)% The&validation&of&molecular&identity(biosimilars /&protein&aggregation)

% Metabolomics of&cells,&serum,&urine&–Large?scale&biobank profiling

% Atomic?level&3D&biomolecular&structure&&&&&% Structure&elucidation&of&nano?scale&/inorganic&materials

! Currently*the*highest*magnetic*field*in*all*of*Ireland*and*NI.

! Equipped*with*1H/15N/13C*cold*(cryo)*probe,*biomolecular*solid*state*MAS*probes,*triple*axial*pulsed!field*gradient*probes,*etc.

! With*the*cold*probe,*capabilities*of*detecting$metabolites$and$in#vivo#sample$concentrations$of$subGμmolar range.

NMR$Metabolomics$: Projects)from)the)Mok)KH)lab.

" High$quality$biobanks: Longitudinal-samples-/-Historical-documentation

Case%Study:%%Renal%Vasculitis%in%Humans(Inflammation+of+the+kidney)

Case%Study:%%Renal%Vasculitis%in%Humans(Inflammation+of+the+kidney)

2 Succesful+identification+of+biomarkers+that+can+be+used+for+diagnosis.

2 Myoinsotol+– Citrate+ratio+in+patient+urine.

Al+Ani++B,+et+al,+Scientific(Reports,+2016

ExperimentsDatabases

PRE-

PROC

ESSI

NGIN

TEGR

ATIO

NIN

TERP

RETA

TION

VISUALISATION

Normalisation Dimensionality reduction

Bayesian Network Fusion Similarity

Assumptions on prior distributions

Posterior probability distribution

Individual networks

Joint network

Alignment of local samples

Fusion of data in uniform

representation

Construction of similarity matrix

Integration of each matrix into a

uniform matrix

Through Bayes theorem

Through e.g. correlation

analysis

e.g. PCA

Omic Data

SUBTYPES BIOMARKERS

INSIGHTS

5

3

4

2

1

General'integration'pipeline'of'the'multiomics in'which(1) Gathering'of'data'through'databases'or'experiments;'(2) Pre=integration'step'to'ensure'correct'integration;'(3) Integration'of'data'through'a'selected'statistical'method;'(4) Visual'representation'of'data'processed'by'the'integrative'tools;(5) Interpretation'of'the'integrated'and'visualised data'to'identify'subtype'and'

biomarkers'as'well'as'new'insights'into'the'studied'disease

Metabolomics, Relatively,Large,Data,Sets,(1)

Originally,**301*Rows*x*507*Columns

Of*these,*in*our*analysis,*use*only*NMR*data

=*301*Rows*x*176*Columns*

Table&2.&Prediction&accuracy&of&sex&of&the&KarMeN&study&participants&based&on&metabolite&profiles&in&plasma&and&urine&using&different&algorithms.


Increases&to&97%


Table&3.&Prediction&of&chronological&age&of&the&KarMeN&study&participants&based&on&metabolite&profiles&in&plasma&and&urine&using&different&algorithms.


S2 Fig.: Concentrations of selected metabolites contained in metabolite patterns

important for prediction of age in male study participants versus age. Plots are

shown for (A) plasma and (B) urine metabolites of male study participants with mean rank

1 (left panel) and 25 (right panel). PO4, phosphate; U2.50, unknown NMR analyte at 2.5

ppm; 4-HMA, 4-hydroxymandelic acid; a.u., arbitrary units.

Urine

Plasma

Improves&to&97&%


Metabolomics Relatively/Large/Data/Sets/(2)

32,700/rows/x/143/subjects

Test/Set/prediction/accuracy/for/lung/cancer:///95%

Perspective*+ Overview! What&biomedical&R&D&has&accomplished&!

Genomics(Personalized&Genome&Screening)

Common&Objectives&of&each&Large&Initiative:! Profiling&of&representative&patient&samples! Compare/Contrast&the&differences! Multivariate&Stat&Analyses! Biomarker&identification&

Proteomics(Not&all&of&the&transcriptome is&translated.)

Transcriptomics(Not&all&of&the&genome&is&expressed.)

Lipidomics /*Gly(c)omics(Not&all&of&the&proteome&is&&glycosylated.)

! Drug*Discoveryand*Development

Perspective*+ Overview! What&biomedical&R&D&has&accomplished&!

Genomics(Personalized&Genome&Screening)

Proteomics(Not&all&of&the&transcriptome is&translated.)

Transcriptomics(Not&all&of&the&genome&is&expressed.)

Lipidomics /*Gly(c)omics(Not&all&of&the&proteome&is&&glycosylated.)

Metabolomics(Manifestation&of&all&of&the&above&+&The&Environment)

Multiomicrepositories-

Emphasis:)Genomics

Emphasis:)Other)Omics

Our$Proposal$–

Marriage'of:

Big'Data'IT'Acquisition'/'Analysis'/'Archiving+

Detailed'and'individualizedbiomedical'data'(='patient'and/or'biobanks)

='''True'interdisciplinary,holistic'vision'&'toolsfor'the'treatmentand'prevention'of''''human'diseases.

전체그림을항상염두에두며,

한 "Omics,(한 –Omics(씩풀어간다.

Trinity'College'Dublin! The%University%of%Dublin%!

! Founded%1592%! Highest%ranked%university%in%Ireland%! Strengths

! Humanities%and%Social%Sciences%%%(Traditional)! Nanosciences! Neurosciences! Biochemistry%&%Immunology

Trinity%Biomedical%Sciences%Institute(TBSI)

Kells사본The'Book'of'Kells

The$Book$of$KellsHoused'in'the'

, Trinity'College'Dublin'Library',

Thank&youfor&yourattention.

Trinity'College,'the'University'of'Dublin

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