aRgus: Multilevel visualization of non-synonymous single nucleotide variants & advanced pathogenicity score modeling for genetic vulnerability assessment
The widespread use of high-throughput sequencing techniques is leading to a rapidly increasing number of disease-associated variants of unknown significance and candidate genes. Integration of knowledge concerning their genetic, protein as well as functional and conservational aspects is necessary f...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-01-01
|
| Series: | Computational and Structural Biotechnology Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037023000235 |
| _version_ | 1797384122356727808 |
|---|---|
| author | Julian Schröter Tal Dattner Jennifer Hüllein Alejandra Jayme Vincent Heuveline Georg F. Hoffmann Stefan Kölker Dominic Lenz Thomas Opladen Bernt Popp Christian P. Schaaf Christian Staufner Steffen Syrbe Sebastian Uhrig Daniel Hübschmann Heiko Brennenstuhl |
| author_facet | Julian Schröter Tal Dattner Jennifer Hüllein Alejandra Jayme Vincent Heuveline Georg F. Hoffmann Stefan Kölker Dominic Lenz Thomas Opladen Bernt Popp Christian P. Schaaf Christian Staufner Steffen Syrbe Sebastian Uhrig Daniel Hübschmann Heiko Brennenstuhl |
| author_sort | Julian Schröter |
| collection | DOAJ |
| description | The widespread use of high-throughput sequencing techniques is leading to a rapidly increasing number of disease-associated variants of unknown significance and candidate genes. Integration of knowledge concerning their genetic, protein as well as functional and conservational aspects is necessary for an exhaustive assessment of their relevance and for prioritization of further clinical and functional studies investigating their role in human disease. To collect the necessary information, a multitude of different databases has to be accessed and data extraction from the original sources commonly is not user-friendly and requires advanced bioinformatics skills. This leads to a decreased data accessibility for a relevant number of potential users such as clinicians, geneticist, and clinical researchers. Here, we present aRgus (https://argus.urz.uni-heidelberg.de/), a standalone webtool for simple extraction and intuitive visualization of multi-layered gene, protein, variant, and variant effect prediction data. aRgus provides interactive exploitation of these data within seconds for any known gene of the human genome. In contrast to existing online platforms for compilation of variant data, aRgus complements visualization of chromosomal exon-intron structure and protein domain annotation with ClinVar and gnomAD variant distributions as well as position-specific variant effect prediction score modeling. aRgus thereby enables timely assessment of protein regions vulnerable to variation with single amino acid resolution and provides numerous applications in variant and protein domain interpretation as well as in the design of in vitro experiments. |
| first_indexed | 2024-03-08T21:30:55Z |
| format | Article |
| id | doaj.art-31fff396829a4de39c3c03926e275ef4 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T21:30:55Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-31fff396829a4de39c3c03926e275ef42023-12-21T07:30:48ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012110771083aRgus: Multilevel visualization of non-synonymous single nucleotide variants & advanced pathogenicity score modeling for genetic vulnerability assessmentJulian Schröter0Tal Dattner1Jennifer Hüllein2Alejandra Jayme3Vincent Heuveline4Georg F. Hoffmann5Stefan Kölker6Dominic Lenz7Thomas Opladen8Bernt Popp9Christian P. Schaaf10Christian Staufner11Steffen Syrbe12Sebastian Uhrig13Daniel Hübschmann14Heiko Brennenstuhl15Division of Pediatric Epileptology, Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, GermanyDivision of Neuropediatrics and Metabolic Medicine, Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, GermanyComputational Oncology, Molecular Precision Oncology Program, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, D-69120 Heidelberg, GermanyEngineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 205, D-69120 Heidelberg, GermanyEngineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 205, D-69120 Heidelberg, GermanyDivision of Neuropediatrics and Metabolic Medicine, Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, GermanyDivision of Neuropediatrics and Metabolic Medicine, Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, GermanyDivision of Neuropediatrics and Metabolic Medicine, Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, GermanyDivision of Neuropediatrics and Metabolic Medicine, Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, GermanyInstitute of Human Genetics, University Medical Center Leipzig, Philipp-Rosenthal-Str. 55 (Haus W), D-04103 Leipzig, GermanyInstitute of Human Genetics, University Hospital Heidelberg, Im Neuenheimer Feld 440, D-69120 Heidelberg, GermanyDivision of Neuropediatrics and Metabolic Medicine, Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, GermanyDivision of Pediatric Epileptology, Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, GermanyComputational Oncology, Molecular Precision Oncology Program, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, D-69120 Heidelberg, GermanyComputational Oncology, Molecular Precision Oncology Program, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, D-69120 Heidelberg, Germany; German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), Im Neuenheimer Feld 280, D-69120 Heidelberg, GermanyDivision of Neuropediatrics and Metabolic Medicine, Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany; Institute of Human Genetics, University Hospital Heidelberg, Im Neuenheimer Feld 440, D-69120 Heidelberg, Germany; Corresponding author at: Institute of Human Genetics, University Hospital Heidelberg, Im Neuenheimer Feld 440, D-69120 Heidelberg, Germany.The widespread use of high-throughput sequencing techniques is leading to a rapidly increasing number of disease-associated variants of unknown significance and candidate genes. Integration of knowledge concerning their genetic, protein as well as functional and conservational aspects is necessary for an exhaustive assessment of their relevance and for prioritization of further clinical and functional studies investigating their role in human disease. To collect the necessary information, a multitude of different databases has to be accessed and data extraction from the original sources commonly is not user-friendly and requires advanced bioinformatics skills. This leads to a decreased data accessibility for a relevant number of potential users such as clinicians, geneticist, and clinical researchers. Here, we present aRgus (https://argus.urz.uni-heidelberg.de/), a standalone webtool for simple extraction and intuitive visualization of multi-layered gene, protein, variant, and variant effect prediction data. aRgus provides interactive exploitation of these data within seconds for any known gene of the human genome. In contrast to existing online platforms for compilation of variant data, aRgus complements visualization of chromosomal exon-intron structure and protein domain annotation with ClinVar and gnomAD variant distributions as well as position-specific variant effect prediction score modeling. aRgus thereby enables timely assessment of protein regions vulnerable to variation with single amino acid resolution and provides numerous applications in variant and protein domain interpretation as well as in the design of in vitro experiments.http://www.sciencedirect.com/science/article/pii/S2001037023000235Pathogenicity scoresVariant effect predictionVariant assessmentComputational genetics |
| spellingShingle | Julian Schröter Tal Dattner Jennifer Hüllein Alejandra Jayme Vincent Heuveline Georg F. Hoffmann Stefan Kölker Dominic Lenz Thomas Opladen Bernt Popp Christian P. Schaaf Christian Staufner Steffen Syrbe Sebastian Uhrig Daniel Hübschmann Heiko Brennenstuhl aRgus: Multilevel visualization of non-synonymous single nucleotide variants & advanced pathogenicity score modeling for genetic vulnerability assessment Computational and Structural Biotechnology Journal Pathogenicity scores Variant effect prediction Variant assessment Computational genetics |
| title | aRgus: Multilevel visualization of non-synonymous single nucleotide variants & advanced pathogenicity score modeling for genetic vulnerability assessment |
| title_full | aRgus: Multilevel visualization of non-synonymous single nucleotide variants & advanced pathogenicity score modeling for genetic vulnerability assessment |
| title_fullStr | aRgus: Multilevel visualization of non-synonymous single nucleotide variants & advanced pathogenicity score modeling for genetic vulnerability assessment |
| title_full_unstemmed | aRgus: Multilevel visualization of non-synonymous single nucleotide variants & advanced pathogenicity score modeling for genetic vulnerability assessment |
| title_short | aRgus: Multilevel visualization of non-synonymous single nucleotide variants & advanced pathogenicity score modeling for genetic vulnerability assessment |
| title_sort | argus multilevel visualization of non synonymous single nucleotide variants amp advanced pathogenicity score modeling for genetic vulnerability assessment |
| topic | Pathogenicity scores Variant effect prediction Variant assessment Computational genetics |
| url | http://www.sciencedirect.com/science/article/pii/S2001037023000235 |
| work_keys_str_mv | AT julianschroter argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT taldattner argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT jenniferhullein argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT alejandrajayme argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT vincentheuveline argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT georgfhoffmann argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT stefankolker argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT dominiclenz argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT thomasopladen argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT berntpopp argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT christianpschaaf argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT christianstaufner argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT steffensyrbe argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT sebastianuhrig argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT danielhubschmann argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment AT heikobrennenstuhl argusmultilevelvisualizationofnonsynonymoussinglenucleotidevariantsampadvancedpathogenicityscoremodelingforgeneticvulnerabilityassessment |