Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping
<p dir="ltr">Proteogenomics studies generate hypotheses on protein function and provide genetic evidence for drug target prioritization. Most previous work has been conducted using affinity-based proteomics approaches. These technologies face challenges, such as uncertainty regarding...
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| مؤلفون آخرون: | , , , , , , , , , , |
| منشور في: |
2024
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| _version_ | 1864513545091153920 |
|---|---|
| author | Karsten Suhre (67967) |
| author2 | Guhan Ram Venkataraman (9009668) Harendra Guturu (451866) Anna Halama (545988) Nisha Stephan (17445912) Gaurav Thareja (459188) Hina Sarwath (4480654) Khatereh Motamedchaboki (266248) Margaret K. R. Donovan (12161084) Asim Siddiqui (25153) Serafim Batzoglou (2585) Frank Schmidt (207186) |
| author2_role | author author author author author author author author author author author |
| author_facet | Karsten Suhre (67967) Guhan Ram Venkataraman (9009668) Harendra Guturu (451866) Anna Halama (545988) Nisha Stephan (17445912) Gaurav Thareja (459188) Hina Sarwath (4480654) Khatereh Motamedchaboki (266248) Margaret K. R. Donovan (12161084) Asim Siddiqui (25153) Serafim Batzoglou (2585) Frank Schmidt (207186) |
| author_role | author |
| dc.creator.none.fl_str_mv | Karsten Suhre (67967) Guhan Ram Venkataraman (9009668) Harendra Guturu (451866) Anna Halama (545988) Nisha Stephan (17445912) Gaurav Thareja (459188) Hina Sarwath (4480654) Khatereh Motamedchaboki (266248) Margaret K. R. Donovan (12161084) Asim Siddiqui (25153) Serafim Batzoglou (2585) Frank Schmidt (207186) |
| dc.date.none.fl_str_mv | 2024-02-02T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41467-024-45233-y |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Nanoparticle_enrichment_mass-spectrometry_proteomics_identifies_protein-altering_variants_for_precise_pQTL_mapping/29446061 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Pharmacology and pharmaceutical sciences Proteogenomics Peptide-centric analysis Affinity-based proteomics Drug target prioritization Cis-protein associations |
| dc.title.none.fl_str_mv | Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Proteogenomics studies generate hypotheses on protein function and provide genetic evidence for drug target prioritization. Most previous work has been conducted using affinity-based proteomics approaches. These technologies face challenges, such as uncertainty regarding target identity, non-specific binding, and handling of variants that affect epitope affinity binding. Mass spectrometry-based proteomics can overcome some of these challenges. Here we report a pQTL study using the Proteograph™ Product Suite workflow (<i>Seer, Inc.</i>) where we quantify over 18,000 unique peptides from nearly 3000 proteins in more than 320 blood samples from a multi-ethnic cohort in a bottom-up, peptide-centric, mass spectrometry-based proteomics approach. We identify 184 protein-altering variants in 137 genes that are significantly associated with their corresponding variant peptides, confirming target specificity of co-associated affinity binders, identifying putatively causal cis-encoded proteins and providing experimental evidence for their presence in blood, including proteins that may be inaccessible to affinity-based proteomics.</p><h2>Other Information</h2><p dir="ltr">Published in: Nature Communications<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41467-024-45233-y" target="_blank">https://dx.doi.org/10.1038/s41467-024-45233-y</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_01ec0ece9f87c8563217fe37e7fe4ddf |
| identifier_str_mv | 10.1038/s41467-024-45233-y |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/29446061 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mappingKarsten Suhre (67967)Guhan Ram Venkataraman (9009668)Harendra Guturu (451866)Anna Halama (545988)Nisha Stephan (17445912)Gaurav Thareja (459188)Hina Sarwath (4480654)Khatereh Motamedchaboki (266248)Margaret K. R. Donovan (12161084)Asim Siddiqui (25153)Serafim Batzoglou (2585)Frank Schmidt (207186)Biological sciencesGeneticsBiomedical and clinical sciencesPharmacology and pharmaceutical sciencesProteogenomicsPeptide-centric analysisAffinity-based proteomicsDrug target prioritizationCis-protein associations<p dir="ltr">Proteogenomics studies generate hypotheses on protein function and provide genetic evidence for drug target prioritization. Most previous work has been conducted using affinity-based proteomics approaches. These technologies face challenges, such as uncertainty regarding target identity, non-specific binding, and handling of variants that affect epitope affinity binding. Mass spectrometry-based proteomics can overcome some of these challenges. Here we report a pQTL study using the Proteograph™ Product Suite workflow (<i>Seer, Inc.</i>) where we quantify over 18,000 unique peptides from nearly 3000 proteins in more than 320 blood samples from a multi-ethnic cohort in a bottom-up, peptide-centric, mass spectrometry-based proteomics approach. We identify 184 protein-altering variants in 137 genes that are significantly associated with their corresponding variant peptides, confirming target specificity of co-associated affinity binders, identifying putatively causal cis-encoded proteins and providing experimental evidence for their presence in blood, including proteins that may be inaccessible to affinity-based proteomics.</p><h2>Other Information</h2><p dir="ltr">Published in: Nature Communications<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41467-024-45233-y" target="_blank">https://dx.doi.org/10.1038/s41467-024-45233-y</a></p>2024-02-02T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41467-024-45233-yhttps://figshare.com/articles/journal_contribution/Nanoparticle_enrichment_mass-spectrometry_proteomics_identifies_protein-altering_variants_for_precise_pQTL_mapping/29446061CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/294460612024-02-02T03:00:00Z |
| spellingShingle | Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping Karsten Suhre (67967) Biological sciences Genetics Biomedical and clinical sciences Pharmacology and pharmaceutical sciences Proteogenomics Peptide-centric analysis Affinity-based proteomics Drug target prioritization Cis-protein associations |
| status_str | publishedVersion |
| title | Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping |
| title_full | Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping |
| title_fullStr | Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping |
| title_full_unstemmed | Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping |
| title_short | Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping |
| title_sort | Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping |
| topic | Biological sciences Genetics Biomedical and clinical sciences Pharmacology and pharmaceutical sciences Proteogenomics Peptide-centric analysis Affinity-based proteomics Drug target prioritization Cis-protein associations |