Dataset Information

Antigen Discovery for Next-Generation Pertussis Vaccines Using Immunoproteomics and Transposon-Directed Insertion Sequencing.

ABSTRACT:

Background

Despite high vaccination rates, the United States has experienced a resurgence in reported cases of pertussis after switching to the acellular pertussis vaccine, indicating a need for improved vaccines that enhance infection control.

Methods

Bordetella pertussis antigens recognized by convalescent-baboon serum and nasopharyngeal wash were identified by immunoproteomics and their subcellular localization predicted. Genes essential or important for persistence in the baboon airway were identified by transposon-directed insertion-site sequencing (TraDIS) analysis.

Results

In total, 314 B. pertussis antigens were identified by convalescent baboon serum and 748 by nasopharyngeal wash. Thirteen antigens were identified as immunogenic in baboons, essential for persistence in the airway by TraDIS, and membrane-localized: BP0840 (OmpP), Pal, OmpA2, BP1485, BamA, Pcp, MlaA, YfgL, BP2197, BP1569, MlaD, ComL, and BP0183.

Conclusions

The B. pertussis antigens identified as immunogenic, essential for persistence in the airway, and membrane-localized warrant further investigation for inclusion in vaccines designed to reduce or prevent carriage of bacteria in the airway of vaccinated individuals.

SUBMITTER: Gregg KA

PROVIDER: S-EPMC10169431 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Antigen Discovery for Next-Generation Pertussis Vaccines Using Immunoproteomics and Transposon-Directed Insertion Sequencing.

Gregg Kelsey A KA Wang Yihui Y Warfel Jason J Schoenfeld Elizabeth E Jankowska Ewa E Cipollo John F JF Mayho Matthew M Boinett Christine C Prasad Deepika D Brickman Timothy J TJ Armstrong Sandra K SK Parkhill Julian J Da Silva Antunes Ricardo R Sette Alessandro A Papin James F JF Wolf Roman R Merkel Tod J TJ

The Journal of infectious diseases 20230201 4

<h4>Background</h4>Despite high vaccination rates, the United States has experienced a resurgence in reported cases of pertussis after switching to the acellular pertussis vaccine, indicating a need for improved vaccines that enhance infection control.<h4>Methods</h4>Bordetella pertussis antigens recognized by convalescent-baboon serum and nasopharyngeal wash were identified by immunoproteomics and their subcellular localization predicted. Genes essential or important for persistence in the babo ...[more]

PMID: 36575950

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Project description:BackgroundNext generation sequencing approaches applied to the analyses of transposon insertion junction fragments generated in high throughput forward genetic screens has created the need for clear informatics and statistical approaches to deal with the massive amount of data currently being generated. Previous approaches utilized to 1) map junction fragments within the genome and 2) identify Common Insertion Sites (CISs) within the genome are not practical due to the volume of data generated by current sequencing technologies. Previous approaches applied to this problem also required significant manual annotation.ResultsWe describe Transposon Annotation Poisson Distribution Association Network Connectivity Environment (TAPDANCE) software, which automates the identification of CISs within transposon junction fragment insertion data. Starting with barcoded sequence data, the software identifies and trims sequences and maps putative genomic sequence to a reference genome using the bowtie short read mapper. Poisson distribution statistics are then applied to assess and rank genomic regions showing significant enrichment for transposon insertion. Novel methods of counting insertions are used to ensure that the results presented have the expected characteristics of informative CISs. A persistent mySQL database is generated and utilized to keep track of sequences, mappings and common insertion sites. Additionally, associations between phenotypes and CISs are also identified using Fisher's exact test with multiple testing correction. In a case study using previously published data we show that the TAPDANCE software identifies CISs as previously described, prioritizes them based on p-value, allows holistic visualization of the data within genome browser software and identifies relationships present in the structure of the data.ConclusionsThe TAPDANCE process is fully automated, performs similarly to previous labor intensive approaches, provides consistent results at a wide range of sequence sampling depth, has the capability of handling extremely large datasets, enables meaningful comparison across datasets and enables large scale meta-analyses of junction fragment data. The TAPDANCE software will greatly enhance our ability to analyze these datasets in order to increase our understanding of the genetic basis of cancers.

Dataset Information

Antigen Discovery for Next-Generation Pertussis Vaccines Using Immunoproteomics and Transposon-Directed Insertion Sequencing.

Background

Methods

Results

Conclusions

Publications

Antigen Discovery for Next-Generation Pertussis Vaccines Using Immunoproteomics and Transposon-Directed Insertion Sequencing.

Similar Datasets

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