Genome-scale search of tumor-specific antigens by collective analysis of mutations, expressions and T-cell recognition

Jia Jia, Juan Cui, Xianghui Liu, Jinhua Han, Shengyong Yang, Yuquan Wei, Yuzong Chen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Tumor-specific antigens (TSAs) are potential sources of cancer vaccines, some of which are derived from T-cell epitopes of over-expressed mutant proteins to elicit immunogenicity and overcome tolerance and evasion. The lack of effective vaccines for many cancers has prompted strong interest in improved TSA search methods. Recent progresses in profiling somatic mutations and expressions of human cancer genomes, and in predicting T-cell epitopes enable genome-scale TSA search by collectively analyzing these profiles. Such a collective approach has not been explored in spite of the availability and usage of individual methods. Methodology: Genome-scale TSA search was conducted by genome-scale search of tumor-specific mutations in differentially over-expressed genes of specific cancers based on tumor-specific somatic mutation and microarray gene expression data, followed by T-cell recognition analysis of the identified mutant and over-expressed peptides to determine if they are substrates of proteasomal cleavage, TAP mediated transport and MHC-I alleles capable of eliciting immune response. The performance of our method was tested against 12 and 4 known T-cell defined melanoma and lung cancer TSAs in the Cancer Immunity database. Conclusions: Our approach identified 50% and 75% of the 12 and 4 known TSAs and predicted from the human cancer genomes additional 8-250 and 14-359 putative TSAs of 5 and 3 HLA alleles respectively. The known TSA hit rates (1.9% and 0.8%) are enriched by 29-fold and 35-fold over those of mutation analysis. The numbers of predicted TSAs are within the testing range of typical screening campaigns. Noises in expression data of small sample sizes appear to be a major factor for misidentification of known TSAs. With improved data quality and analysis methods, the collective approach is potentially useful for facilitating genome-scale TSA search.

Original languageEnglish (US)
Pages (from-to)1824-1829
Number of pages6
JournalMolecular Immunology
Volume46
Issue number8-9
DOIs
StatePublished - May 1 2009

Fingerprint

Neoplasm Antigens
Genome
T-Lymphocytes
Mutation
Cancer Vaccines
T-Lymphocyte Epitopes
Human Genome
Neoplasms
Alleles
Neoplasm Genes
Mutant Proteins
Sample Size
Noise
Immunity
Melanoma
Lung Neoplasms
Databases
Gene Expression
Peptides

Keywords

  • Cancer vaccines
  • Human cancer genomes
  • Tumor-specific antigens

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Cite this

Genome-scale search of tumor-specific antigens by collective analysis of mutations, expressions and T-cell recognition. / Jia, Jia; Cui, Juan; Liu, Xianghui; Han, Jinhua; Yang, Shengyong; Wei, Yuquan; Chen, Yuzong.

In: Molecular Immunology, Vol. 46, No. 8-9, 01.05.2009, p. 1824-1829.

Research output: Contribution to journalArticle

Jia, Jia ; Cui, Juan ; Liu, Xianghui ; Han, Jinhua ; Yang, Shengyong ; Wei, Yuquan ; Chen, Yuzong. / Genome-scale search of tumor-specific antigens by collective analysis of mutations, expressions and T-cell recognition. In: Molecular Immunology. 2009 ; Vol. 46, No. 8-9. pp. 1824-1829.
@article{86029aea7da4430ab3aa6474149e62c9,
title = "Genome-scale search of tumor-specific antigens by collective analysis of mutations, expressions and T-cell recognition",
abstract = "Background: Tumor-specific antigens (TSAs) are potential sources of cancer vaccines, some of which are derived from T-cell epitopes of over-expressed mutant proteins to elicit immunogenicity and overcome tolerance and evasion. The lack of effective vaccines for many cancers has prompted strong interest in improved TSA search methods. Recent progresses in profiling somatic mutations and expressions of human cancer genomes, and in predicting T-cell epitopes enable genome-scale TSA search by collectively analyzing these profiles. Such a collective approach has not been explored in spite of the availability and usage of individual methods. Methodology: Genome-scale TSA search was conducted by genome-scale search of tumor-specific mutations in differentially over-expressed genes of specific cancers based on tumor-specific somatic mutation and microarray gene expression data, followed by T-cell recognition analysis of the identified mutant and over-expressed peptides to determine if they are substrates of proteasomal cleavage, TAP mediated transport and MHC-I alleles capable of eliciting immune response. The performance of our method was tested against 12 and 4 known T-cell defined melanoma and lung cancer TSAs in the Cancer Immunity database. Conclusions: Our approach identified 50{\%} and 75{\%} of the 12 and 4 known TSAs and predicted from the human cancer genomes additional 8-250 and 14-359 putative TSAs of 5 and 3 HLA alleles respectively. The known TSA hit rates (1.9{\%} and 0.8{\%}) are enriched by 29-fold and 35-fold over those of mutation analysis. The numbers of predicted TSAs are within the testing range of typical screening campaigns. Noises in expression data of small sample sizes appear to be a major factor for misidentification of known TSAs. With improved data quality and analysis methods, the collective approach is potentially useful for facilitating genome-scale TSA search.",
keywords = "Cancer vaccines, Human cancer genomes, Tumor-specific antigens",
author = "Jia Jia and Juan Cui and Xianghui Liu and Jinhua Han and Shengyong Yang and Yuquan Wei and Yuzong Chen",
year = "2009",
month = "5",
day = "1",
doi = "10.1016/j.molimm.2009.01.019",
language = "English (US)",
volume = "46",
pages = "1824--1829",
journal = "Molecular Immunology",
issn = "0161-5890",
publisher = "Elsevier Limited",
number = "8-9",

}

TY - JOUR

T1 - Genome-scale search of tumor-specific antigens by collective analysis of mutations, expressions and T-cell recognition

AU - Jia, Jia

AU - Cui, Juan

AU - Liu, Xianghui

AU - Han, Jinhua

AU - Yang, Shengyong

AU - Wei, Yuquan

AU - Chen, Yuzong

PY - 2009/5/1

Y1 - 2009/5/1

N2 - Background: Tumor-specific antigens (TSAs) are potential sources of cancer vaccines, some of which are derived from T-cell epitopes of over-expressed mutant proteins to elicit immunogenicity and overcome tolerance and evasion. The lack of effective vaccines for many cancers has prompted strong interest in improved TSA search methods. Recent progresses in profiling somatic mutations and expressions of human cancer genomes, and in predicting T-cell epitopes enable genome-scale TSA search by collectively analyzing these profiles. Such a collective approach has not been explored in spite of the availability and usage of individual methods. Methodology: Genome-scale TSA search was conducted by genome-scale search of tumor-specific mutations in differentially over-expressed genes of specific cancers based on tumor-specific somatic mutation and microarray gene expression data, followed by T-cell recognition analysis of the identified mutant and over-expressed peptides to determine if they are substrates of proteasomal cleavage, TAP mediated transport and MHC-I alleles capable of eliciting immune response. The performance of our method was tested against 12 and 4 known T-cell defined melanoma and lung cancer TSAs in the Cancer Immunity database. Conclusions: Our approach identified 50% and 75% of the 12 and 4 known TSAs and predicted from the human cancer genomes additional 8-250 and 14-359 putative TSAs of 5 and 3 HLA alleles respectively. The known TSA hit rates (1.9% and 0.8%) are enriched by 29-fold and 35-fold over those of mutation analysis. The numbers of predicted TSAs are within the testing range of typical screening campaigns. Noises in expression data of small sample sizes appear to be a major factor for misidentification of known TSAs. With improved data quality and analysis methods, the collective approach is potentially useful for facilitating genome-scale TSA search.

AB - Background: Tumor-specific antigens (TSAs) are potential sources of cancer vaccines, some of which are derived from T-cell epitopes of over-expressed mutant proteins to elicit immunogenicity and overcome tolerance and evasion. The lack of effective vaccines for many cancers has prompted strong interest in improved TSA search methods. Recent progresses in profiling somatic mutations and expressions of human cancer genomes, and in predicting T-cell epitopes enable genome-scale TSA search by collectively analyzing these profiles. Such a collective approach has not been explored in spite of the availability and usage of individual methods. Methodology: Genome-scale TSA search was conducted by genome-scale search of tumor-specific mutations in differentially over-expressed genes of specific cancers based on tumor-specific somatic mutation and microarray gene expression data, followed by T-cell recognition analysis of the identified mutant and over-expressed peptides to determine if they are substrates of proteasomal cleavage, TAP mediated transport and MHC-I alleles capable of eliciting immune response. The performance of our method was tested against 12 and 4 known T-cell defined melanoma and lung cancer TSAs in the Cancer Immunity database. Conclusions: Our approach identified 50% and 75% of the 12 and 4 known TSAs and predicted from the human cancer genomes additional 8-250 and 14-359 putative TSAs of 5 and 3 HLA alleles respectively. The known TSA hit rates (1.9% and 0.8%) are enriched by 29-fold and 35-fold over those of mutation analysis. The numbers of predicted TSAs are within the testing range of typical screening campaigns. Noises in expression data of small sample sizes appear to be a major factor for misidentification of known TSAs. With improved data quality and analysis methods, the collective approach is potentially useful for facilitating genome-scale TSA search.

KW - Cancer vaccines

KW - Human cancer genomes

KW - Tumor-specific antigens

UR - http://www.scopus.com/inward/record.url?scp=64149120251&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=64149120251&partnerID=8YFLogxK

U2 - 10.1016/j.molimm.2009.01.019

DO - 10.1016/j.molimm.2009.01.019

M3 - Article

C2 - 19243822

AN - SCOPUS:64149120251

VL - 46

SP - 1824

EP - 1829

JO - Molecular Immunology

JF - Molecular Immunology

SN - 0161-5890

IS - 8-9

ER -