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Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping.
Suhre, Karsten; Venkataraman, Guhan Ram; Guturu, Harendra; Halama, Anna; Stephan, Nisha; Thareja, Gaurav; Sarwath, Hina; Motamedchaboki, Khatereh; Donovan, Margaret K R; Siddiqui, Asim; Batzoglou, Serafim; Schmidt, Frank.
Affiliation
  • Suhre K; Bioinformatics Core, Weill Cornell Medicine-Qatar, Education City, 24144, Doha, Qatar. kas2049@qatar-med.cornell.edu.
  • Venkataraman GR; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA. kas2049@qatar-med.cornell.edu.
  • Guturu H; Seer, Inc., Redwood City, Redwood City, CA, 94065, USA.
  • Halama A; Seer, Inc., Redwood City, Redwood City, CA, 94065, USA.
  • Stephan N; Bioinformatics Core, Weill Cornell Medicine-Qatar, Education City, 24144, Doha, Qatar.
  • Thareja G; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.
  • Sarwath H; Bioinformatics Core, Weill Cornell Medicine-Qatar, Education City, 24144, Doha, Qatar.
  • Motamedchaboki K; Bioinformatics Core, Weill Cornell Medicine-Qatar, Education City, 24144, Doha, Qatar.
  • Donovan MKR; Proteomics Core, Weill Cornell Medicine-Qatar, Education City, 24144, Doha, Qatar.
  • Siddiqui A; Seer, Inc., Redwood City, Redwood City, CA, 94065, USA.
  • Batzoglou S; Seer, Inc., Redwood City, Redwood City, CA, 94065, USA.
  • Schmidt F; Seer, Inc., Redwood City, Redwood City, CA, 94065, USA.
Nat Commun ; 15(1): 989, 2024 Feb 02.
Article in En | MEDLINE | ID: mdl-38307861
ABSTRACT
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 (Seer, Inc.) 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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proteomics / Proteogenomics Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Affiliation country: Qatar

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proteomics / Proteogenomics Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Affiliation country: Qatar