{"doi":"10.1101/2021.10.01.462481","title":"Prevalence, persistence, and genetics of antibody responses to protein toxins and virulence factors","abstract":"Abstract Microbial exposures are crucial environmental factors that impact healthspan by sculpting the immune system and microbiota. Antibody profiling via programmable Phage ImmunoPrecipitation Sequencing (PhIP-Seq) provides a high-throughput, costeffective approach for multiplexed detection of exposure and response to thousands of microbial protein products. Here we designed and constructed a library of 95,601 56 amino acid peptide tiles spanning a subset of environmental proteins more likely to be associated with immune responses: those with “toxin” or “virulence factor” keyword annotations. PhIP-Seq was used to profile the circulating antibodies of ~1,000 individuals against this “ToxScan” library of 14,430 toxins and virulence factors from 1,312 genera of organisms. In addition to a detailed analysis of six commonly encountered human commensals and pathogens, we study the age-dependent stability of the ToxScan profile and use a genome-wide association study (GWAS) to find that the MHC-II locus modulates the selection of bacterial epitopes. We detect previously described anti-flagellin antibody responses in a Crohn’s disease cohort and identify a novel association between anti-flagellin antibodies and juvenile dermatomyositis (JDM). PhIP-Seq with the ToxScan library provides a new window into exposure and immune responses to environmental protein toxins and virulence factors, which can be used to study human health and disease at cohort scale.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":216858,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":108422,"name":"Daniel R. Monaco","orcid":null,"position":1,"is_corresponding":false},{"id":555589,"name":"Athena Chen","orcid":"0000-0001-6900-2264","position":2,"is_corresponding":false},{"id":813228,"name":"Thiagarajan Venkataraman","orcid":"0000-0003-0921-6345","position":3,"is_corresponding":false},{"id":808762,"name":"Sahana Jayaraman","orcid":"0000-0003-3413-2530","position":4,"is_corresponding":false},{"id":813229,"name":"Cristian Valencia","orcid":"0000-0002-0813-6151","position":5,"is_corresponding":false},{"id":108417,"name":"Brandon Sie","orcid":"0000-0001-9405-1850","position":6,"is_corresponding":false},{"id":332024,"name":"Thomas Liechti","orcid":"0000-0001-8738-6679","position":7,"is_corresponding":false},{"id":778345,"name":"Payam Noroozi Farhadi","orcid":"0000-0003-2419-050X","position":8,"is_corresponding":false},{"id":735727,"name":"Gabriela Funez-dePagnier","orcid":null,"position":9,"is_corresponding":false},{"id":813230,"name":"Cheryl A. Sherman‐Baust","orcid":"0000-0001-7977-4698","position":10,"is_corresponding":false},{"id":813815,"name":"May Q. Wong","orcid":null,"position":11,"is_corresponding":false},{"id":86850,"name":"Cynthia L. Sears","orcid":"0000-0003-4059-1661","position":12,"is_corresponding":false},{"id":305631,"name":"Patricia J. Simner","orcid":"0000-0001-6134-151X","position":13,"is_corresponding":false},{"id":253554,"name":"June L. Round","orcid":"0000-0002-7158-9874","position":14,"is_corresponding":false},{"id":115227,"name":"Priya Duggal","orcid":"0000-0001-5809-2081","position":15,"is_corresponding":false},{"id":105290,"name":"Uri Laserson","orcid":"0000-0002-8429-7686","position":16,"is_corresponding":false},{"id":805727,"name":"Theodore S. Steiner","orcid":"0000-0002-3136-6668","position":17,"is_corresponding":false},{"id":264587,"name":"Ranjan Sen","orcid":"0000-0002-1916-3905","position":18,"is_corresponding":false},{"id":257667,"name":"Thomas E. Lloyd","orcid":"0000-0003-4756-3700","position":19,"is_corresponding":false},{"id":18050,"name":"Mario Roederer","orcid":"0000-0001-7448-7040","position":20,"is_corresponding":false},{"id":257669,"name":"Andrew L. Mammen","orcid":"0000-0003-3732-3252","position":21,"is_corresponding":false},{"id":627483,"name":"Randy Longman","orcid":"0000-0002-9042-184X","position":22,"is_corresponding":false},{"id":264511,"name":"Lisa G. Rider","orcid":"0000-0002-6912-2458","position":23,"is_corresponding":false},{"id":108428,"name":"H. Benjamin Larman","orcid":"0000-0001-7863-196X","position":24,"is_corresponding":false},{"id":813227,"name":"Julia W. Angkeow","orcid":"0009-0002-8274-1859","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:15.868165Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}