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An open-source computational and data resource to analyze digital maps of immunopeptidomes.

Caron E, Espona L, Kowalewski DJ, Schuster H, Ternette N, Alpízar A, Schittenhelm RB, Ramarathinam SH, Lindestam Arlehamn CS, Chiek Koh C, Gillet LC, Rabsteyn A, Navarro P, Kim S, Lam H, Sturm T, Marcilla M, Sette A, Campbell DS, Deutsch EW, Moritz RL, Purcell AW, Rammensee HG, Stevanovic S, Aebersold R - Elife (2015)

Bottom Line: We present a novel mass spectrometry-based high-throughput workflow and an open-source computational and data resource to reproducibly identify and quantify HLA-associated peptides.Collectively, the resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated from a range of biological sources by SWATH mass spectrometry (MS).This study represents the first community-based effort to develop a robust platform for the reproducible and quantitative measurement of the entire repertoire of peptides presented by HLA molecules, an essential step towards the design of efficient immunotherapies.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zurich, Switzerland.

ABSTRACT
We present a novel mass spectrometry-based high-throughput workflow and an open-source computational and data resource to reproducibly identify and quantify HLA-associated peptides. Collectively, the resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated from a range of biological sources by SWATH mass spectrometry (MS). This study represents the first community-based effort to develop a robust platform for the reproducible and quantitative measurement of the entire repertoire of peptides presented by HLA molecules, an essential step towards the design of efficient immunotherapies.

No MeSH data available.


Related in: MedlinePlus

Binding scores of naturally presented HLA-A and -B peptides contained in individual source proteins.We assessed the predicted HLA binding affinity of all peptides contained in individual source proteins. The pie chart shows the proportion of naturally presented peptides isolated by immunoaffinity chromatography that ranked in the top 1% (blue), top 5% (red), top 10% (yellow), or below the 90th percentile of peptides (pale blue).DOI:http://dx.doi.org/10.7554/eLife.07661.019
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fig2s6: Binding scores of naturally presented HLA-A and -B peptides contained in individual source proteins.We assessed the predicted HLA binding affinity of all peptides contained in individual source proteins. The pie chart shows the proportion of naturally presented peptides isolated by immunoaffinity chromatography that ranked in the top 1% (blue), top 5% (red), top 10% (yellow), or below the 90th percentile of peptides (pale blue).DOI:http://dx.doi.org/10.7554/eLife.07661.019

Mentions: (A) HLA peptides were isolated by immunoaffinity chromatography and were annotated to their respective HLA alleles following DDA mass spectrometry. (B) Heat map visualization of HLA class I peptides identified from 20 HLA-typed biological samples. HLA-A and -B alleles are indicated for each sample. (C) 35,812 distinct class I and class II HLA peptides were identified, annotated, and used to build 32 and 11 HLA allele-specific peptide spectral and SWATH assay libraries, respectively. (D) The distribution curve shows that 95% of the HLA-B07-annotated peptides were predicted to bind the HLA molecule with an IC50 below 531 nM. Inner pie chart: we assessed the predicted HLA binding affinity of all peptides contained in individual source proteins. The pie chart shows that 92% of naturally presented HLA-B07 peptides were ranked in the top 1% (blue) of predicted peptides (see also Figure 2—figure supplement 6).


An open-source computational and data resource to analyze digital maps of immunopeptidomes.

Caron E, Espona L, Kowalewski DJ, Schuster H, Ternette N, Alpízar A, Schittenhelm RB, Ramarathinam SH, Lindestam Arlehamn CS, Chiek Koh C, Gillet LC, Rabsteyn A, Navarro P, Kim S, Lam H, Sturm T, Marcilla M, Sette A, Campbell DS, Deutsch EW, Moritz RL, Purcell AW, Rammensee HG, Stevanovic S, Aebersold R - Elife (2015)

Binding scores of naturally presented HLA-A and -B peptides contained in individual source proteins.We assessed the predicted HLA binding affinity of all peptides contained in individual source proteins. The pie chart shows the proportion of naturally presented peptides isolated by immunoaffinity chromatography that ranked in the top 1% (blue), top 5% (red), top 10% (yellow), or below the 90th percentile of peptides (pale blue).DOI:http://dx.doi.org/10.7554/eLife.07661.019
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507788&req=5

fig2s6: Binding scores of naturally presented HLA-A and -B peptides contained in individual source proteins.We assessed the predicted HLA binding affinity of all peptides contained in individual source proteins. The pie chart shows the proportion of naturally presented peptides isolated by immunoaffinity chromatography that ranked in the top 1% (blue), top 5% (red), top 10% (yellow), or below the 90th percentile of peptides (pale blue).DOI:http://dx.doi.org/10.7554/eLife.07661.019
Mentions: (A) HLA peptides were isolated by immunoaffinity chromatography and were annotated to their respective HLA alleles following DDA mass spectrometry. (B) Heat map visualization of HLA class I peptides identified from 20 HLA-typed biological samples. HLA-A and -B alleles are indicated for each sample. (C) 35,812 distinct class I and class II HLA peptides were identified, annotated, and used to build 32 and 11 HLA allele-specific peptide spectral and SWATH assay libraries, respectively. (D) The distribution curve shows that 95% of the HLA-B07-annotated peptides were predicted to bind the HLA molecule with an IC50 below 531 nM. Inner pie chart: we assessed the predicted HLA binding affinity of all peptides contained in individual source proteins. The pie chart shows that 92% of naturally presented HLA-B07 peptides were ranked in the top 1% (blue) of predicted peptides (see also Figure 2—figure supplement 6).

Bottom Line: We present a novel mass spectrometry-based high-throughput workflow and an open-source computational and data resource to reproducibly identify and quantify HLA-associated peptides.Collectively, the resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated from a range of biological sources by SWATH mass spectrometry (MS).This study represents the first community-based effort to develop a robust platform for the reproducible and quantitative measurement of the entire repertoire of peptides presented by HLA molecules, an essential step towards the design of efficient immunotherapies.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zurich, Switzerland.

ABSTRACT
We present a novel mass spectrometry-based high-throughput workflow and an open-source computational and data resource to reproducibly identify and quantify HLA-associated peptides. Collectively, the resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated from a range of biological sources by SWATH mass spectrometry (MS). This study represents the first community-based effort to develop a robust platform for the reproducible and quantitative measurement of the entire repertoire of peptides presented by HLA molecules, an essential step towards the design of efficient immunotherapies.

No MeSH data available.


Related in: MedlinePlus