Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements

Damir Baranasic; Matthias Hörtenhuber; Piotr J. Balwierz; Tobias Zehnder; Abdul Kadir Mukarram; Chirag Nepal; Csilla Várnai; Yavor Hadzhiev; Ada Jimenez-Gonzalez; Nan Li; Joseph Wragg; Fabio M. D’Orazio; Dorde Relic; Mikhail Pachkov; Noelia Díaz; Benjamín Hernández-Rodríguez; Zelin Chen; Marcus Stoiber; Michaël Dong; Irene Stevens; Samuel E. Ross; Anne Eagle; Ryan Martin; Oluwapelumi Obasaju; Sepand Rastegar; Alison C. McGarvey; Wolfgang Kopp; Emily Chambers; Dennis Wang; Hyejeong R. Kim; Rafael D. Acemel; Silvia Naranjo; Maciej Łapiński; Vanessa Chong; Sinnakaruppan Mathavan; Bernard Peers; Tatjana Sauka-Spengler; Martin Vingron; Piero Carninci; Uwe Ohler; Scott Allen Lacadie; Shawn M. Burgess; Cecilia Winata; Freek van Eeden; Juan M. Vaquerizas; José Luis Gómez-Skarmeta; Daria Onichtchouk; Ben James Brown; Ozren Bogdanovic; Erik van Nimwegen; Monte Westerfield; Fiona C. Wardle; Carsten O. Daub; Boris Lenhard; Ferenc Müller

doi:10.1038/s41588-022-01089-w

Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements

Damir Baranasic, Matthias Hörtenhuber, Piotr J. Balwierz, Tobias Zehnder, Abdul Kadir Mukarram, Chirag Nepal, Csilla Várnai, Yavor Hadzhiev, Ada Jimenez-Gonzalez, Nan Li, Joseph Wragg, Fabio M. D’Orazio, Dorde Relic, Mikhail Pachkov, Noelia Díaz, Benjamín Hernández-Rodríguez, Zelin Chen, Marcus Stoiber, Michaël Dong, Irene StevensSamuel E. Ross, Anne Eagle, Ryan Martin, Oluwapelumi Obasaju, Sepand Rastegar, Alison C. McGarvey, Wolfgang Kopp, Emily Chambers, Dennis Wang, Hyejeong R. Kim, Rafael D. Acemel, Silvia Naranjo, Maciej Łapiński, Vanessa Chong, Sinnakaruppan Mathavan, Bernard Peers, Tatjana Sauka-Spengler, Martin Vingron, Piero Carninci, Uwe Ohler, Scott Allen Lacadie, Shawn M. Burgess, Cecilia Winata, Freek van Eeden, Juan M. Vaquerizas, José Luis Gómez-Skarmeta, Daria Onichtchouk, Ben James Brown, Ozren Bogdanovic, Erik van Nimwegen, Monte Westerfield, Fiona C. Wardle, Carsten O. Daub, Boris Lenhard^*, Ferenc Müller

^*Corresponding author for this work

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Abstract

Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental functional genomic data. Our data coordination center (https://danio-code.zfin.org) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals.

Original language	English
Pages (from-to)	1037-1050
Number of pages	14
Journal	Nature Genetics
Volume	54
Issue number	7
DOIs	https://doi.org/10.1038/s41588-022-01089-w
Publication status	Published - 4 Jul 2022

Bibliographical note

Funding Information:
We are indebted to the late Jose Luis Gomez Skarmeta for his devoted support of the DANIO-CODE programme. We thank M. Haussler at UCSC and D. Zerbino at EBI for facilitating access of DANIO-CODE track hubs in the UCSC and Ensembl genome browsers, respectively. We thank ZFIN for hosting the DANIO-CODE DCC and raw data. We thank J. Horsefield for creating the DANIO-CODE logo. We thank data producers (for the list of laboratories visit the DANIO-CODE DCC) who directly uploaded data and provided metadata directly. We thank DNANexus for providing computer time for the reprocessing of public datasets. We thank our main funders, the Horizon 2020 MSCA-ITN project ZENCODE-ITN by the European Commission to F.M., B.L., C.O.D., J.M.V. and B.P. (GA no: 643062), BBSRC support (DanioPeaks, P61715) to B.L., F.M. and F.C.W., Wellcome Trust (Joint-Investigator award 106955/Z/15/Z) to F.M. and B.L. and AQUA-FAANG (Horizon 2020, GA 817923) to B.L., D.B. and F.M. and BBSRC (BB/R015457/1) to F.vE and Key Special Project for Introduced Talents Team to Z.C. (GML2019ZD0401) and PrecisionTox project by the European Commission (GA no: 965406 ) . We thank SNP&SEQ Technology Platform in Uppsala, Sweden (CAGE sequencing), MRC LMS Genomics Facility and Genomics Birmingham facilities UK. D.B. was awarded the Rutherford Fund Fellowship.

Publisher Copyright:
© 2022, Crown.

Keywords

Animals
Chromatin/genetics
Databases, Genetic
Gene Expression Regulation, Developmental
Genome/genetics
Genomics
Humans
Mice
Molecular Sequence Annotation
Organogenesis/genetics
Regulatory Sequences, Nucleic Acid/genetics
Zebrafish/embryology
Zebrafish Proteins/genetics

ASJC Scopus subject areas

Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41588-022-01089-wLicence: Creative Commons: Attribution (CC BY)

BaranasicD2022MultiomicFinal published version, 37.9 MBLicence: Creative Commons: Attribution (CC BY)

H2020_COLLAB_AQUA-FAANG
Müller, F.
European Commission
1/04/19 → 31/10/23
Project: EU
The core promoter: an unexplored regulatory level of transcription during vertebrate development
Müller, F.
THE WELLCOME TRUST, Imperial College
1/12/15 → 31/10/21
Project: Research
H2020_ITN_ZENCODE
Kanhere, A. & Müller, F.
European Commission - Management Costs, European Commission
1/01/15 → 31/12/18
Project: Research

Cite this

Baranasic, D., Hörtenhuber, M., Balwierz, P. J., Zehnder, T., Mukarram, A. K., Nepal, C., Várnai, C., Hadzhiev, Y., Jimenez-Gonzalez, A., Li, N., Wragg, J., D’Orazio, F. M., Relic, D., Pachkov, M., Díaz, N., Hernández-Rodríguez, B., Chen, Z., Stoiber, M., Dong, M., ... Müller, F. (2022). Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements. Nature Genetics, 54(7), 1037-1050. https://doi.org/10.1038/s41588-022-01089-w

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abstract = "Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental functional genomic data. Our data coordination center (https://danio-code.zfin.org) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals.",

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author = "Damir Baranasic and Matthias H{\"o}rtenhuber and Balwierz, {Piotr J.} and Tobias Zehnder and Mukarram, {Abdul Kadir} and Chirag Nepal and Csilla V{\'a}rnai and Yavor Hadzhiev and Ada Jimenez-Gonzalez and Nan Li and Joseph Wragg and D{\textquoteright}Orazio, {Fabio M.} and Dorde Relic and Mikhail Pachkov and Noelia D{\'i}az and Benjam{\'i}n Hern{\'a}ndez-Rodr{\'i}guez and Zelin Chen and Marcus Stoiber and Micha{\"e}l Dong and Irene Stevens and Ross, {Samuel E.} and Anne Eagle and Ryan Martin and Oluwapelumi Obasaju and Sepand Rastegar and McGarvey, {Alison C.} and Wolfgang Kopp and Emily Chambers and Dennis Wang and Kim, {Hyejeong R.} and Acemel, {Rafael D.} and Silvia Naranjo and Maciej {\L}api{\'n}ski and Vanessa Chong and Sinnakaruppan Mathavan and Bernard Peers and Tatjana Sauka-Spengler and Martin Vingron and Piero Carninci and Uwe Ohler and Lacadie, {Scott Allen} and Burgess, {Shawn M.} and Cecilia Winata and {van Eeden}, Freek and Vaquerizas, {Juan M.} and G{\'o}mez-Skarmeta, {Jos{\'e} Luis} and Daria Onichtchouk and Brown, {Ben James} and Ozren Bogdanovic and {van Nimwegen}, Erik and Monte Westerfield and Wardle, {Fiona C.} and Daub, {Carsten O.} and Boris Lenhard and Ferenc M{\"u}ller",

note = "Funding Information: We are indebted to the late Jose Luis Gomez Skarmeta for his devoted support of the DANIO-CODE programme. We thank M. Haussler at UCSC and D. Zerbino at EBI for facilitating access of DANIO-CODE track hubs in the UCSC and Ensembl genome browsers, respectively. We thank ZFIN for hosting the DANIO-CODE DCC and raw data. We thank J. Horsefield for creating the DANIO-CODE logo. We thank data producers (for the list of laboratories visit the DANIO-CODE DCC) who directly uploaded data and provided metadata directly. We thank DNANexus for providing computer time for the reprocessing of public datasets. We thank our main funders, the Horizon 2020 MSCA-ITN project ZENCODE-ITN by the European Commission to F.M., B.L., C.O.D., J.M.V. and B.P. (GA no: 643062), BBSRC support (DanioPeaks, P61715) to B.L., F.M. and F.C.W., Wellcome Trust (Joint-Investigator award 106955/Z/15/Z) to F.M. and B.L. and AQUA-FAANG (Horizon 2020, GA 817923) to B.L., D.B. and F.M. and BBSRC (BB/R015457/1) to F.vE and Key Special Project for Introduced Talents Team to Z.C. (GML2019ZD0401) and PrecisionTox project by the European Commission (GA no: 965406 ) . We thank SNP&SEQ Technology Platform in Uppsala, Sweden (CAGE sequencing), MRC LMS Genomics Facility and Genomics Birmingham facilities UK. D.B. was awarded the Rutherford Fund Fellowship. Publisher Copyright: {\textcopyright} 2022, Crown.",

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doi = "10.1038/s41588-022-01089-w",

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Baranasic, D, Hörtenhuber, M, Balwierz, PJ, Zehnder, T, Mukarram, AK, Nepal, C, Várnai, C , Hadzhiev, Y, Jimenez-Gonzalez, A, Li, N, Wragg, J, D’Orazio, FM, Relic, D, Pachkov, M, Díaz, N, Hernández-Rodríguez, B, Chen, Z, Stoiber, M, Dong, M, Stevens, I, Ross, SE, Eagle, A, Martin, R, Obasaju, O, Rastegar, S, McGarvey, AC, Kopp, W, Chambers, E, Wang, D, Kim, HR, Acemel, RD, Naranjo, S, Łapiński, M, Chong, V, Mathavan, S, Peers, B, Sauka-Spengler, T, Vingron, M, Carninci, P, Ohler, U, Lacadie, SA, Burgess, SM, Winata, C, van Eeden, F, Vaquerizas, JM, Gómez-Skarmeta, JL, Onichtchouk, D, Brown, BJ, Bogdanovic, O, van Nimwegen, E, Westerfield, M, Wardle, FC, Daub, CO, Lenhard, B & Müller, F 2022, 'Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements', Nature Genetics, vol. 54, no. 7, pp. 1037-1050. https://doi.org/10.1038/s41588-022-01089-w

TY - JOUR

T1 - Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements

AU - Baranasic, Damir

AU - Hörtenhuber, Matthias

AU - Balwierz, Piotr J.

AU - Zehnder, Tobias

AU - Mukarram, Abdul Kadir

AU - Nepal, Chirag

AU - Várnai, Csilla

AU - Hadzhiev, Yavor

AU - Jimenez-Gonzalez, Ada

AU - Li, Nan

AU - Wragg, Joseph

AU - D’Orazio, Fabio M.

AU - Relic, Dorde

AU - Pachkov, Mikhail

AU - Díaz, Noelia

AU - Hernández-Rodríguez, Benjamín

AU - Chen, Zelin

AU - Stoiber, Marcus

AU - Dong, Michaël

AU - Stevens, Irene

AU - Ross, Samuel E.

AU - Eagle, Anne

AU - Martin, Ryan

AU - Obasaju, Oluwapelumi

AU - Rastegar, Sepand

AU - McGarvey, Alison C.

AU - Kopp, Wolfgang

AU - Chambers, Emily

AU - Wang, Dennis

AU - Kim, Hyejeong R.

AU - Acemel, Rafael D.

AU - Naranjo, Silvia

AU - Łapiński, Maciej

AU - Chong, Vanessa

AU - Mathavan, Sinnakaruppan

AU - Peers, Bernard

AU - Sauka-Spengler, Tatjana

AU - Vingron, Martin

AU - Carninci, Piero

AU - Ohler, Uwe

AU - Lacadie, Scott Allen

AU - Burgess, Shawn M.

AU - Winata, Cecilia

AU - van Eeden, Freek

AU - Vaquerizas, Juan M.

AU - Gómez-Skarmeta, José Luis

AU - Onichtchouk, Daria

AU - Brown, Ben James

AU - Bogdanovic, Ozren

AU - van Nimwegen, Erik

AU - Westerfield, Monte

AU - Wardle, Fiona C.

AU - Daub, Carsten O.

AU - Lenhard, Boris

AU - Müller, Ferenc

N1 - Funding Information: We are indebted to the late Jose Luis Gomez Skarmeta for his devoted support of the DANIO-CODE programme. We thank M. Haussler at UCSC and D. Zerbino at EBI for facilitating access of DANIO-CODE track hubs in the UCSC and Ensembl genome browsers, respectively. We thank ZFIN for hosting the DANIO-CODE DCC and raw data. We thank J. Horsefield for creating the DANIO-CODE logo. We thank data producers (for the list of laboratories visit the DANIO-CODE DCC) who directly uploaded data and provided metadata directly. We thank DNANexus for providing computer time for the reprocessing of public datasets. We thank our main funders, the Horizon 2020 MSCA-ITN project ZENCODE-ITN by the European Commission to F.M., B.L., C.O.D., J.M.V. and B.P. (GA no: 643062), BBSRC support (DanioPeaks, P61715) to B.L., F.M. and F.C.W., Wellcome Trust (Joint-Investigator award 106955/Z/15/Z) to F.M. and B.L. and AQUA-FAANG (Horizon 2020, GA 817923) to B.L., D.B. and F.M. and BBSRC (BB/R015457/1) to F.vE and Key Special Project for Introduced Talents Team to Z.C. (GML2019ZD0401) and PrecisionTox project by the European Commission (GA no: 965406 ) . We thank SNP&SEQ Technology Platform in Uppsala, Sweden (CAGE sequencing), MRC LMS Genomics Facility and Genomics Birmingham facilities UK. D.B. was awarded the Rutherford Fund Fellowship. Publisher Copyright: © 2022, Crown.

PY - 2022/7/4

Y1 - 2022/7/4

N2 - Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental functional genomic data. Our data coordination center (https://danio-code.zfin.org) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals.

AB - Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental functional genomic data. Our data coordination center (https://danio-code.zfin.org) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals.

KW - Animals

KW - Chromatin/genetics

KW - Databases, Genetic

KW - Gene Expression Regulation, Developmental

KW - Genome/genetics

KW - Genomics

KW - Humans

KW - Mice

KW - Molecular Sequence Annotation

KW - Organogenesis/genetics

KW - Regulatory Sequences, Nucleic Acid/genetics

KW - Zebrafish/embryology

KW - Zebrafish Proteins/genetics

UR - http://www.scopus.com/inward/record.url?scp=85133345316&partnerID=8YFLogxK

U2 - 10.1038/s41588-022-01089-w

DO - 10.1038/s41588-022-01089-w

M3 - Article

C2 - 35789323

AN - SCOPUS:85133345316

SN - 1061-4036

VL - 54

SP - 1037

EP - 1050

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -

Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Fingerprint

Projects

H2020_COLLAB_AQUA-FAANG

The core promoter: an unexplored regulatory level of transcription during vertebrate development

H2020_ITN_ZENCODE

Cite this