Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques
Аутори
Rauner, MartinaFoessl, Ines
Formosa, Melissa
Kague, Erika
Prijatelj, Vid
Alonso Lopez, Nerea
Banerjee, Bodhisattwa
Bergen, Dylan
Busse, Björn
Calado, Angelo
Douni, Eleni
Gabet, Yankel
Garcı´a Giralt, Natalia
Grinberg, Daniel
Lovsin, Nika
Nogues Solan, Xavier
Ostanek, Barbara
Pavlos, Nathan
Rivadeneira, Fernando
Soldatović, Ivan
van de Peppel, Jeroen
van der Eerden, Bram
van Hul, Wim
Balcells, Susanna
Marc, Janja
Reppe, Sjur
Søe, Kent
Karasik, David
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The availability of large human datasets for genome-wide association studies (GWAS) and the advancement of sequencing technologies have boosted the identification of genetic variants in complex and rare diseases in the skeletal field. Yet, interpreting results from human association studies remains a challenge. To bridge the gap between genetic association and causality, a systematic functional investigation is necessary. Multiple unknowns exist for putative causal genes, including cellular localization of the molecular function. Intermediate traits (“endophenotypes”), e.g. molecular quantitative trait loci (molQTLs), are needed to identify mechanisms of underlying associations. Furthermore, index variants often reside in non-coding regions of the genome, therefore challenging for interpretation. Knowledge of non-coding variance (e.g. ncRNAs), repetitive sequences, and regulatory interactions between enhancers and their target genes is central for understanding causal genes in skeletal... conditions. Animal models with deep skeletal phenotyping and cell culture models have already facilitated fine mapping of some association signals, elucidated gene mechanisms, and revealed disease-relevant biology. However, to accelerate research towards bridging the current gap between association and causality in skeletal diseases, alternative in vivo platforms need to be used and developed in parallel with the current -omics and traditional in vivo resources. Therefore, we argue that as a field we need to establish resource-sharing standards to collectively address complex research questions. These standards will promote data integration from various -omics technologies and functional dissection of human complex traits. In this mission statement, we review the current available resources and as a group propose a consensus to facilitate resource sharing using existing and future resources. Such coordination efforts will maximize the acquisition of knowledge from different approaches and thus reduce redundancy and duplication of resources. These measures will help to understand the pathogenesis of osteoporosis and other skeletal diseases towards defining new and more efficient therapeutic targets.
Кључне речи:
animal models / data integration analysis / gene regulation / genome-wide association study / musculoskeletal diseaseИзвор:
Frontiers in Endocrinology, 2021, 12Издавач:
- Frontiers Media S.A.
DOI: 10.3389/fendo.2021.731217
ISSN: 1664-2392
WoS: 000731742100001
Scopus: 2-s2.0-85121622954
Институција/група
PharmacyTY - JOUR AU - Rauner, Martina AU - Foessl, Ines AU - Formosa, Melissa AU - Kague, Erika AU - Prijatelj, Vid AU - Alonso Lopez, Nerea AU - Banerjee, Bodhisattwa AU - Bergen, Dylan AU - Busse, Björn AU - Calado, Angelo AU - Douni, Eleni AU - Gabet, Yankel AU - Garcı´a Giralt, Natalia AU - Grinberg, Daniel AU - Lovsin, Nika AU - Nogues Solan, Xavier AU - Ostanek, Barbara AU - Pavlos, Nathan AU - Rivadeneira, Fernando AU - Soldatović, Ivan AU - van de Peppel, Jeroen AU - van der Eerden, Bram AU - van Hul, Wim AU - Balcells, Susanna AU - Marc, Janja AU - Reppe, Sjur AU - Søe, Kent AU - Karasik, David PY - 2021 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4019 AB - The availability of large human datasets for genome-wide association studies (GWAS) and the advancement of sequencing technologies have boosted the identification of genetic variants in complex and rare diseases in the skeletal field. Yet, interpreting results from human association studies remains a challenge. To bridge the gap between genetic association and causality, a systematic functional investigation is necessary. Multiple unknowns exist for putative causal genes, including cellular localization of the molecular function. Intermediate traits (“endophenotypes”), e.g. molecular quantitative trait loci (molQTLs), are needed to identify mechanisms of underlying associations. Furthermore, index variants often reside in non-coding regions of the genome, therefore challenging for interpretation. Knowledge of non-coding variance (e.g. ncRNAs), repetitive sequences, and regulatory interactions between enhancers and their target genes is central for understanding causal genes in skeletal conditions. Animal models with deep skeletal phenotyping and cell culture models have already facilitated fine mapping of some association signals, elucidated gene mechanisms, and revealed disease-relevant biology. However, to accelerate research towards bridging the current gap between association and causality in skeletal diseases, alternative in vivo platforms need to be used and developed in parallel with the current -omics and traditional in vivo resources. Therefore, we argue that as a field we need to establish resource-sharing standards to collectively address complex research questions. These standards will promote data integration from various -omics technologies and functional dissection of human complex traits. In this mission statement, we review the current available resources and as a group propose a consensus to facilitate resource sharing using existing and future resources. Such coordination efforts will maximize the acquisition of knowledge from different approaches and thus reduce redundancy and duplication of resources. These measures will help to understand the pathogenesis of osteoporosis and other skeletal diseases towards defining new and more efficient therapeutic targets. PB - Frontiers Media S.A. T2 - Frontiers in Endocrinology T1 - Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques VL - 12 DO - 10.3389/fendo.2021.731217 ER -
@article{ author = "Rauner, Martina and Foessl, Ines and Formosa, Melissa and Kague, Erika and Prijatelj, Vid and Alonso Lopez, Nerea and Banerjee, Bodhisattwa and Bergen, Dylan and Busse, Björn and Calado, Angelo and Douni, Eleni and Gabet, Yankel and Garcı´a Giralt, Natalia and Grinberg, Daniel and Lovsin, Nika and Nogues Solan, Xavier and Ostanek, Barbara and Pavlos, Nathan and Rivadeneira, Fernando and Soldatović, Ivan and van de Peppel, Jeroen and van der Eerden, Bram and van Hul, Wim and Balcells, Susanna and Marc, Janja and Reppe, Sjur and Søe, Kent and Karasik, David", year = "2021", abstract = "The availability of large human datasets for genome-wide association studies (GWAS) and the advancement of sequencing technologies have boosted the identification of genetic variants in complex and rare diseases in the skeletal field. Yet, interpreting results from human association studies remains a challenge. To bridge the gap between genetic association and causality, a systematic functional investigation is necessary. Multiple unknowns exist for putative causal genes, including cellular localization of the molecular function. Intermediate traits (“endophenotypes”), e.g. molecular quantitative trait loci (molQTLs), are needed to identify mechanisms of underlying associations. Furthermore, index variants often reside in non-coding regions of the genome, therefore challenging for interpretation. Knowledge of non-coding variance (e.g. ncRNAs), repetitive sequences, and regulatory interactions between enhancers and their target genes is central for understanding causal genes in skeletal conditions. Animal models with deep skeletal phenotyping and cell culture models have already facilitated fine mapping of some association signals, elucidated gene mechanisms, and revealed disease-relevant biology. However, to accelerate research towards bridging the current gap between association and causality in skeletal diseases, alternative in vivo platforms need to be used and developed in parallel with the current -omics and traditional in vivo resources. Therefore, we argue that as a field we need to establish resource-sharing standards to collectively address complex research questions. These standards will promote data integration from various -omics technologies and functional dissection of human complex traits. In this mission statement, we review the current available resources and as a group propose a consensus to facilitate resource sharing using existing and future resources. Such coordination efforts will maximize the acquisition of knowledge from different approaches and thus reduce redundancy and duplication of resources. These measures will help to understand the pathogenesis of osteoporosis and other skeletal diseases towards defining new and more efficient therapeutic targets.", publisher = "Frontiers Media S.A.", journal = "Frontiers in Endocrinology", title = "Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques", volume = "12", doi = "10.3389/fendo.2021.731217" }
Rauner, M., Foessl, I., Formosa, M., Kague, E., Prijatelj, V., Alonso Lopez, N., Banerjee, B., Bergen, D., Busse, B., Calado, A., Douni, E., Gabet, Y., Garcı´a Giralt, N., Grinberg, D., Lovsin, N., Nogues Solan, X., Ostanek, B., Pavlos, N., Rivadeneira, F., Soldatović, I., van de Peppel, J., van der Eerden, B., van Hul, W., Balcells, S., Marc, J., Reppe, S., Søe, K.,& Karasik, D.. (2021). Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques. in Frontiers in Endocrinology Frontiers Media S.A.., 12. https://doi.org/10.3389/fendo.2021.731217
Rauner M, Foessl I, Formosa M, Kague E, Prijatelj V, Alonso Lopez N, Banerjee B, Bergen D, Busse B, Calado A, Douni E, Gabet Y, Garcı´a Giralt N, Grinberg D, Lovsin N, Nogues Solan X, Ostanek B, Pavlos N, Rivadeneira F, Soldatović I, van de Peppel J, van der Eerden B, van Hul W, Balcells S, Marc J, Reppe S, Søe K, Karasik D. Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques. in Frontiers in Endocrinology. 2021;12. doi:10.3389/fendo.2021.731217 .
Rauner, Martina, Foessl, Ines, Formosa, Melissa, Kague, Erika, Prijatelj, Vid, Alonso Lopez, Nerea, Banerjee, Bodhisattwa, Bergen, Dylan, Busse, Björn, Calado, Angelo, Douni, Eleni, Gabet, Yankel, Garcı´a Giralt, Natalia, Grinberg, Daniel, Lovsin, Nika, Nogues Solan, Xavier, Ostanek, Barbara, Pavlos, Nathan, Rivadeneira, Fernando, Soldatović, Ivan, van de Peppel, Jeroen, van der Eerden, Bram, van Hul, Wim, Balcells, Susanna, Marc, Janja, Reppe, Sjur, Søe, Kent, Karasik, David, "Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques" in Frontiers in Endocrinology, 12 (2021), https://doi.org/10.3389/fendo.2021.731217 . .