Abstract
BackgroundIn the biopharmaceutical industry, biomarkers define molecular taxonomies of patients and diseases and serve as surrogate endpoints in early-phase drug trials. Molecular biomarkers can be much more sensitive than traditional lab tests. Discriminating disease biomarkers by traditional method such as DNA microarray has proved challenging. Alternative splicing isoform represents a new class of diagnostic biomarkers. Recent scientific evidence is demonstrating that the differentiation and quantification of individual alternative splicing isoforms could improve insights into disease diagnosis and management. Identifying and characterizing alternative splicing isoforms are essential to the study of molecular mechanisms and early detection of complex diseases such as breast cancer. However, there are limitations with traditional methods used for alternative splicing isoform determination such as transcriptome-level, low level of coverage and poor focus on alternative splicing.ResultsTherefore, we presented a peptidomics approach to searching novel alternative splicing isoforms in clinical proteomics. Our results showed that the approach has significant potential in enabling discovery of new types of high-quality alternative splicing isoform biomarkers.ConclusionsWe developed a peptidomics approach for the proteomics community to analyze, identify, and characterize alternative splicing isoforms from MS-based proteomics experiments with more coverage and exclusive focus on alternative splicing. The approach can help generate novel hypotheses on molecular risk factors and molecular mechanisms of cancer in early stage, leading to identification of potentially highly specific alternative splicing isoform biomarkers for early detection of cancer.
Highlights
A biomarker as defined by the National Cancer Institute is “a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease [1].” It is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention [2]
80 plasma samples were collected (40 samples collected from women with breast cancer and 40 from healthy volunteer woman who served as controls)
An independent validation dataset of 80 samples which contains 40 samples collected from women diagnosed with breast cancer and 40 from healthy volunteer woman who served as controls were collected by the Hoosier Oncology Group (HOG) (Indianapolis, IN, USA) too and is comparable to the study in the demography and clinical distribution of breast cancer stages/subtypes
Summary
The 80 breast cancer plasma samples with 40 samples from women diagnosed with breast cancer and 40 from healthy volunteer women as controls were searched by OMSSA[40] against the SASD database. The eight peptides, identified by OMSSA, have significant difference in the numbers of hit samples between healthy women and breast cancers (pvalue < 0.05, Table 1). Discussions We described the peptidomics approach to searching novel alternative splicing isoform in proteomics data, especially artificial alternative splicing and SNP We can use it to identify two types of common alternative splicing events: Exon Skipping and Intron Retention. The current protein sequence databases used by tandem mass spectra search engines, for example IPI, UniProt, and NCBI nr, are designed to be useful as possible to as many researchers as possible. ERBB2 EP300 BRCA2 EP300 ERBB2 EP300 includes majority of all occurrence of alternative splicing It provides alternative splicing for each peptide, such as splicing mode, splicing type, splicing site, starting position, ending position, and peptide sequence. All authors are involved in the drafting and revisions of the manuscript
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
