Deciphering the impact of genomic variation on function

UM1HG011969; UM1HG011966; Single Cell; QTL/Statgen; Phenotypic Impact and Function; Neuro; Noncoding Variants; MPRA; iPSC; Impact on Diverse Populations; Immune; Imaging; Evolution; Enumerating Variants; Defining and Systematizing Function; CRISPR; Coding Variants; Cellular Programs and Networks; Cardiometabolic; Standards and Pipelines; Networks; Mapping; Project Design; Computational Analysis, Modeling, and Prediction; Characterization; Catalog; Code of Conduct Committee (alphabetical by last name); Steering Committee Co-Chairs (alphabetical by last name); IGVF Consortium; NHGRI Program Management (alphabetical by last name); IGVF Affiliate Member Projects (contact PIs, other members (alphabetical by last name)); Data and Administrative Coordinating Center Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)); Network Projects (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)); Predictive Modeling Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)); Mapping Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)); Characterization Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)); Working Group and Focus Group Co-Chairs (alphabetical by last name); Writing group (ordered by contribution); Yi lab; Xu lab; Seruggia lab; Sanjana lab; Reilly lab; Ray lab; Pollard lab; Pennacchio and Visel lab; Mostafavi lab; Moore lab; Jones lab; Heinig lab; Gupta lab; Grimes lab; Gazal lab; Dey lab; Ciccia lab; Brennand lab; U24HG012070; U24HG012012; U01HG012103; U01HG012079; U01HG012059; U01HG012051; U01HG012047; U01HG012041; U01HG012069; U01HG012064; U01HG012039; U01HG012022; U01HG012009; U01HG011967; U01HG011952; UM1HG012077; UM1HG012076; UM1HG011986; UM1HG012053; UM1HG012010; UM1HG012003; UM1HG011996; UM1HG011989; UM1HG011972

doi:10.1038/s41586-024-07510-0

Deciphering the impact of genomic variation on function

UM1HG011969, UM1HG011966, Single Cell, QTL/Statgen, Phenotypic Impact and Function, Neuro, Noncoding Variants, MPRA, iPSC, Impact on Diverse Populations, Immune, Imaging, Evolution, Enumerating Variants, Defining and Systematizing Function, CRISPR, Coding Variants, Cellular Programs and Networks, Cardiometabolic, Standards and PipelinesNetworks, Mapping, Project Design, Computational Analysis, Modeling, and Prediction, Characterization, Catalog, Code of Conduct Committee (alphabetical by last name), Steering Committee Co-Chairs (alphabetical by last name), IGVF Consortium, NHGRI Program Management (alphabetical by last name), IGVF Affiliate Member Projects (contact PIs, other members (alphabetical by last name)), Data and Administrative Coordinating Center Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)), Network Projects (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)), Predictive Modeling Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)), Mapping Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)), Characterization Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)), Working Group and Focus Group Co-Chairs (alphabetical by last name), Writing group (ordered by contribution), Yi lab, Xu lab, Seruggia lab, Sanjana lab, Reilly lab, Ray lab, Pollard lab, Pennacchio and Visel lab, Mostafavi lab, Moore lab, Jones lab, Heinig lab, Gupta lab, Grimes lab, Gazal lab, Dey lab, Ciccia lab, Brennand lab, U24HG012070, U24HG012012, U01HG012103, U01HG012079, U01HG012059, U01HG012051, U01HG012047, U01HG012041, U01HG012069, U01HG012064, U01HG012039, U01HG012022, U01HG012009, U01HG011967, U01HG011952, UM1HG012077, UM1HG012076, UM1HG011986, UM1HG012053, UM1HG012010, UM1HG012003, UM1HG011996, UM1HG011989, UM1HG011972

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Our genomes influence nearly every aspect of human biology—from molecular and cellular functions to phenotypes in health and disease. Studying the differences in DNA sequence between individuals (genomic variation) could reveal previously unknown mechanisms of human biology, uncover the basis of genetic predispositions to diseases, and guide the development of new diagnostic tools and therapeutic agents. Yet, understanding how genomic variation alters genome function to influence phenotype has proved challenging. To unlock these insights, we need a systematic and comprehensive catalogue of genome function and the molecular and cellular effects of genomic variants. Towards this goal, the Impact of Genomic Variation on Function (IGVF) Consortium will combine approaches in single-cell mapping, genomic perturbations and predictive modelling to investigate the relationships among genomic variation, genome function and phenotypes. IGVF will create maps across hundreds of cell types and states describing how coding variants alter protein activity, how noncoding variants change the regulation of gene expression, and how such effects connect through gene-regulatory and protein-interaction networks. These experimental data, computational predictions and accompanying standards and pipelines will be integrated into an open resource that will catalyse community efforts to explore how our genomes influence biology and disease across populations.

Original language	English
Pages (from-to)	47-57
Number of pages	11
Journal	Nature
Volume	633
Issue number	8028
DOIs	https://doi.org/10.1038/s41586-024-07510-0
State	Published - 5 Sep 2024

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10.1038/s41586-024-07510-0

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UM1HG011969, UM1HG011966, Single Cell, QTL/Statgen, Phenotypic Impact and Function, Neuro, Noncoding Variants, MPRA, iPSC, Impact on Diverse Populations, Immune, Imaging, Evolution, Enumerating Variants, Defining and Systematizing Function, CRISPR, Coding Variants, Cellular Programs and Networks, Cardiometabolic, ... UM1HG011972 (2024). Deciphering the impact of genomic variation on function. Nature, 633(8028), 47-57. https://doi.org/10.1038/s41586-024-07510-0

@article{a5e20013b8f54c4086046dbbaa7f8e1b,

title = "Deciphering the impact of genomic variation on function",

abstract = "Our genomes influence nearly every aspect of human biology—from molecular and cellular functions to phenotypes in health and disease. Studying the differences in DNA sequence between individuals (genomic variation) could reveal previously unknown mechanisms of human biology, uncover the basis of genetic predispositions to diseases, and guide the development of new diagnostic tools and therapeutic agents. Yet, understanding how genomic variation alters genome function to influence phenotype has proved challenging. To unlock these insights, we need a systematic and comprehensive catalogue of genome function and the molecular and cellular effects of genomic variants. Towards this goal, the Impact of Genomic Variation on Function (IGVF) Consortium will combine approaches in single-cell mapping, genomic perturbations and predictive modelling to investigate the relationships among genomic variation, genome function and phenotypes. IGVF will create maps across hundreds of cell types and states describing how coding variants alter protein activity, how noncoding variants change the regulation of gene expression, and how such effects connect through gene-regulatory and protein-interaction networks. These experimental data, computational predictions and accompanying standards and pipelines will be integrated into an open resource that will catalyse community efforts to explore how our genomes influence biology and disease across populations.",

author = "UM1HG011969 and UM1HG011966 and {Single Cell} and QTL/Statgen and {Phenotypic Impact and Function} and Neuro and {Noncoding Variants} and MPRA and iPSC and {Impact on Diverse Populations} and Immune and Imaging and Evolution and {Enumerating Variants} and {Defining and Systematizing Function} and CRISPR and {Coding Variants} and {Cellular Programs and Networks} and Cardiometabolic and {Standards and Pipelines} and Networks and Mapping and {Project Design} and {Computational Analysis, Modeling, and Prediction} and Characterization and Catalog and {Code of Conduct Committee (alphabetical by last name)} and {Steering Committee Co-Chairs (alphabetical by last name)} and {IGVF Consortium} and {NHGRI Program Management (alphabetical by last name)} and {IGVF Affiliate Member Projects (contact PIs, other members (alphabetical by last name))} and {Data and Administrative Coordinating Center Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name))} and {Network Projects (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name))} and {Predictive Modeling Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name))} and {Mapping Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name))} and {Characterization Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name))} and {Working Group and Focus Group Co-Chairs (alphabetical by last name)} and {Writing group (ordered by contribution)} and {Yi lab} and {Xu lab} and {Seruggia lab} and {Sanjana lab} and {Reilly lab} and {Ray lab} and {Pollard lab} and {Pennacchio and Visel lab} and {Mostafavi lab} and {Moore lab} and {Jones lab} and {Heinig lab} and {Gupta lab} and {Grimes lab} and {Gazal lab} and {Dey lab} and {Ciccia lab} and {Brennand lab} and U24HG012070 and U24HG012012 and U01HG012103 and U01HG012079 and U01HG012059 and U01HG012051 and U01HG012047 and U01HG012041 and U01HG012069 and U01HG012064 and U01HG012039 and U01HG012022 and U01HG012009 and U01HG011967 and U01HG011952 and UM1HG012077 and UM1HG012076 and UM1HG011986 and UM1HG012053 and UM1HG012010 and UM1HG012003 and UM1HG011996 and UM1HG011989 and UM1HG011972 and Samer, {Ella K.} and Morris, {Stephanie A.} and Hutter, {Carolyn M.} and Gilchrist, {Daniel A.} and Stephanie Calluori and Zo Bly and Daniel Osorio and Liang Zhang and Wei He and Rongjie Fu and Han Xu and Sandra Wittibschlager and Kutschat, {Ana Patricia} and Davide Seruggia and Morris, {John A.} and Christina Caragine and Sanjana, {Neville E.} and Ho, {Ching Huang} and Harten, {Ingrid A.} and John Ray and Sean Whalen and Shiron Drusinsky and Pollard, {Katherine S.} and Axel Visel and Neil Slaven and Brandon Mannion and Michael Kosicki and Momoe Kato and Pennacchio, {Len A.} and Anna Spiro and Alexander Sasse and Sara Mostafavi and Susie Song and Elizabeth Roberts and Maddie Murphy and Elisa Donnard and Jones, {Thouis R.} and Corinna Losert and Matthias Heinig and Vivian Lee-Kim and Shi Fang and Rajat Gupta and Nathan Salomonis and Grimes, {H. Leighton} and Artem Kim and Ali, {Thahmina A.} and Dey, {Kushal K.} and Alina Vaitsiankova and Kristen Brennand and Vikas Pejaver",

note = "Publisher Copyright: {\textcopyright} Springer Nature Limited 2024.",

year = "2024",

month = sep,

day = "5",

doi = "10.1038/s41586-024-07510-0",

language = "English",

volume = "633",

pages = "47--57",

journal = "Nature",

issn = "0028-0836",

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UM1HG011969, UM1HG011966, Single Cell, QTL/Statgen, Phenotypic Impact and Function, Neuro, Noncoding Variants, MPRA, iPSC, Impact on Diverse Populations, Immune, Imaging, Evolution, Enumerating Variants, Defining and Systematizing Function, CRISPR, Coding Variants, Cellular Programs and Networks, Cardiometabolic, Standards and Pipelines, Networks, Mapping, Project Design, Computational Analysis, Modeling, and Prediction, Characterization, Catalog, Code of Conduct Committee (alphabetical by last name), Steering Committee Co-Chairs (alphabetical by last name), IGVF Consortium, NHGRI Program Management (alphabetical by last name), IGVF Affiliate Member Projects (contact PIs, other members (alphabetical by last name)), Data and Administrative Coordinating Center Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)), Network Projects (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)), Predictive Modeling Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)), Mapping Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)), Characterization Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name)), Working Group and Focus Group Co-Chairs (alphabetical by last name), Writing group (ordered by contribution), Yi lab, Xu lab, Seruggia lab, Sanjana lab, Reilly lab, Ray lab, Pollard lab, Pennacchio and Visel lab, Mostafavi lab, Moore lab, Jones lab, Heinig lab, Gupta lab, Grimes lab, Gazal lab, Dey lab, Ciccia lab, Brennand lab, U24HG012070, U24HG012012, U01HG012103, U01HG012079, U01HG012059, U01HG012051, U01HG012047, U01HG012041, U01HG012069, U01HG012064, U01HG012039, U01HG012022, U01HG012009, U01HG011967, U01HG011952, UM1HG012077, UM1HG012076, UM1HG011986, UM1HG012053, UM1HG012010, UM1HG012003, UM1HG011996, UM1HG011989 & UM1HG011972 2024, 'Deciphering the impact of genomic variation on function', Nature, vol. 633, no. 8028, pp. 47-57. https://doi.org/10.1038/s41586-024-07510-0

TY - JOUR

T1 - Deciphering the impact of genomic variation on function

AU - UM1HG011969

AU - UM1HG011966

AU - Single Cell

AU - QTL/Statgen

AU - Phenotypic Impact and Function

AU - Neuro

AU - Noncoding Variants

AU - MPRA

AU - iPSC

AU - Impact on Diverse Populations

AU - Immune

AU - Imaging

AU - Evolution

AU - Enumerating Variants

AU - Defining and Systematizing Function

AU - CRISPR

AU - Coding Variants

AU - Cellular Programs and Networks

AU - Cardiometabolic

AU - Standards and Pipelines

AU - Networks

AU - Mapping

AU - Project Design

AU - Computational Analysis, Modeling, and Prediction

AU - Characterization

AU - Catalog

AU - Code of Conduct Committee (alphabetical by last name)

AU - Steering Committee Co-Chairs (alphabetical by last name)

AU - IGVF Consortium

AU - NHGRI Program Management (alphabetical by last name)

AU - IGVF Affiliate Member Projects (contact PIs, other members (alphabetical by last name))

AU - Data and Administrative Coordinating Center Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name))

AU - Network Projects (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name))

AU - Predictive Modeling Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name))

AU - Mapping Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name))

AU - Characterization Awards (contact PI, MPIs (alphabetical by last name), other members (alphabetical by last name))

AU - Working Group and Focus Group Co-Chairs (alphabetical by last name)

AU - Writing group (ordered by contribution)

AU - Yi lab

AU - Xu lab

AU - Seruggia lab

AU - Sanjana lab

AU - Reilly lab

AU - Ray lab

AU - Pollard lab

AU - Pennacchio and Visel lab

AU - Mostafavi lab

AU - Moore lab

AU - Jones lab

AU - Heinig lab

AU - Gupta lab

AU - Grimes lab

AU - Gazal lab

AU - Dey lab

AU - Ciccia lab

AU - Brennand lab

AU - U24HG012070

AU - U24HG012012

AU - U01HG012103

AU - U01HG012079

AU - U01HG012059

AU - U01HG012051

AU - U01HG012047

AU - U01HG012041

AU - U01HG012069

AU - U01HG012064

AU - U01HG012039

AU - U01HG012022

AU - U01HG012009

AU - U01HG011967

AU - U01HG011952

AU - UM1HG012077

AU - UM1HG012076

AU - UM1HG011986

AU - UM1HG012053

AU - UM1HG012010

AU - UM1HG012003

AU - UM1HG011996

AU - UM1HG011989

AU - UM1HG011972

AU - Samer, Ella K.

AU - Morris, Stephanie A.

AU - Hutter, Carolyn M.

AU - Gilchrist, Daniel A.

AU - Calluori, Stephanie

AU - Bly, Zo

AU - Osorio, Daniel

AU - Zhang, Liang

AU - He, Wei

AU - Fu, Rongjie

AU - Xu, Han

AU - Wittibschlager, Sandra

AU - Kutschat, Ana Patricia

AU - Seruggia, Davide

AU - Morris, John A.

AU - Caragine, Christina

AU - Sanjana, Neville E.

AU - Ho, Ching Huang

AU - Harten, Ingrid A.

AU - Ray, John

AU - Whalen, Sean

AU - Drusinsky, Shiron

AU - Pollard, Katherine S.

AU - Visel, Axel

AU - Slaven, Neil

AU - Mannion, Brandon

AU - Kosicki, Michael

AU - Kato, Momoe

AU - Pennacchio, Len A.

AU - Spiro, Anna

AU - Sasse, Alexander

AU - Mostafavi, Sara

AU - Song, Susie

AU - Roberts, Elizabeth

AU - Murphy, Maddie

AU - Donnard, Elisa

AU - Jones, Thouis R.

AU - Losert, Corinna

AU - Heinig, Matthias

AU - Lee-Kim, Vivian

AU - Fang, Shi

AU - Gupta, Rajat

AU - Salomonis, Nathan

AU - Grimes, H. Leighton

AU - Kim, Artem

AU - Ali, Thahmina A.

AU - Dey, Kushal K.

AU - Vaitsiankova, Alina

AU - Brennand, Kristen

AU - Pejaver, Vikas

PY - 2024/9/5

Y1 - 2024/9/5

N2 - Our genomes influence nearly every aspect of human biology—from molecular and cellular functions to phenotypes in health and disease. Studying the differences in DNA sequence between individuals (genomic variation) could reveal previously unknown mechanisms of human biology, uncover the basis of genetic predispositions to diseases, and guide the development of new diagnostic tools and therapeutic agents. Yet, understanding how genomic variation alters genome function to influence phenotype has proved challenging. To unlock these insights, we need a systematic and comprehensive catalogue of genome function and the molecular and cellular effects of genomic variants. Towards this goal, the Impact of Genomic Variation on Function (IGVF) Consortium will combine approaches in single-cell mapping, genomic perturbations and predictive modelling to investigate the relationships among genomic variation, genome function and phenotypes. IGVF will create maps across hundreds of cell types and states describing how coding variants alter protein activity, how noncoding variants change the regulation of gene expression, and how such effects connect through gene-regulatory and protein-interaction networks. These experimental data, computational predictions and accompanying standards and pipelines will be integrated into an open resource that will catalyse community efforts to explore how our genomes influence biology and disease across populations.

AB - Our genomes influence nearly every aspect of human biology—from molecular and cellular functions to phenotypes in health and disease. Studying the differences in DNA sequence between individuals (genomic variation) could reveal previously unknown mechanisms of human biology, uncover the basis of genetic predispositions to diseases, and guide the development of new diagnostic tools and therapeutic agents. Yet, understanding how genomic variation alters genome function to influence phenotype has proved challenging. To unlock these insights, we need a systematic and comprehensive catalogue of genome function and the molecular and cellular effects of genomic variants. Towards this goal, the Impact of Genomic Variation on Function (IGVF) Consortium will combine approaches in single-cell mapping, genomic perturbations and predictive modelling to investigate the relationships among genomic variation, genome function and phenotypes. IGVF will create maps across hundreds of cell types and states describing how coding variants alter protein activity, how noncoding variants change the regulation of gene expression, and how such effects connect through gene-regulatory and protein-interaction networks. These experimental data, computational predictions and accompanying standards and pipelines will be integrated into an open resource that will catalyse community efforts to explore how our genomes influence biology and disease across populations.

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U2 - 10.1038/s41586-024-07510-0

DO - 10.1038/s41586-024-07510-0

M3 - Article

C2 - 39232149

AN - SCOPUS:85203374698

SN - 0028-0836

VL - 633

SP - 47

EP - 57

JO - Nature

JF - Nature

IS - 8028

ER -

Deciphering the impact of genomic variation on function

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