scholarly journals iTTCA-RF: a random forest predictor for tumor T cell antigens

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shihu Jiao ◽  
Quan Zou ◽  
Huannan Guo ◽  
Lei Shi

Abstract Background Cancer is one of the most serious diseases threatening human health. Cancer immunotherapy represents the most promising treatment strategy due to its high efficacy and selectivity and lower side effects compared with traditional treatment. The identification of tumor T cell antigens is one of the most important tasks for antitumor vaccines development and molecular function investigation. Although several machine learning predictors have been developed to identify tumor T cell antigen, more accurate tumor T cell antigen identification by existing methodology is still challenging. Methods In this study, we used a non-redundant dataset of 592 tumor T cell antigens (positive samples) and 393 tumor T cell antigens (negative samples). Four types feature encoding methods have been studied to build an efficient predictor, including amino acid composition, global protein sequence descriptors and grouped amino acid and peptide composition. To improve the feature representation ability of the hybrid features, we further employed a two-step feature selection technique to search for the optimal feature subset. The final prediction model was constructed using random forest algorithm. Results Finally, the top 263 informative features were selected to train the random forest classifier for detecting tumor T cell antigen peptides. iTTCA-RF provides satisfactory performance, with balanced accuracy, specificity and sensitivity values of 83.71%, 78.73% and 88.69% over tenfold cross-validation as well as 73.14%, 62.67% and 83.61% over independent tests, respectively. The online prediction server was freely accessible at http://lab.malab.cn/~acy/iTTCA. Conclusions We have proven that the proposed predictor iTTCA-RF is superior to the other latest models, and will hopefully become an effective and useful tool for identifying tumor T cell antigens presented in the context of major histocompatibility complex class I.

2013 ◽  
Vol 804 ◽  
pp. 70-75 ◽  
Author(s):  
Jian-Hua Huang ◽  
Hua-Lin Xie ◽  
Jun Yan ◽  
Hong-Mei Lu ◽  
Qing-Song Xu ◽  
...  

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4549-4549
Author(s):  
Henry Y. Dong ◽  
Patti Cohen ◽  
Po-Shing Lee

Abstract Lineage commitment of B- and T-lymphocytes occurs in early stages of normal differentiation. Pax-5 promotes commitment of B-cell and blocks early development of T-cell. Under neoplastic conditions, aberrant expression of less specific T-cell antigens (CD2, CD5 and CD8) has been detected in certain B-cell lymphomas, and B-cell antigens CD20 and CD79a have been seen in rare cases of T-cell lymphomas. However, coexpression of true lineage specific B-cell antigens Pax-5 and CD19 in T-cells with surface CD3 and T-cell receptors has not been reported in either normal or neoplastic T-cells. We report 4 cases of aggressive T-cell lymphoma/leukemia with a consistent but unusual immunophenotype, which was determined by immunohistochemistry (IHC) in all four cases with paraffin embedded tissue and by flow cytometry (FCM) in 2/4 cases. Molecular and cytogenetic analyses were also attempted in two patients and clinical information will be provided. All patients were male aged 21-79 years. Three patients, including 2 cases of T-ALL, presented with generalized lymphadenopathy and bone marrow involvement (clinical stage IV); 1/3 also had splenic involvement. A distinct mediastinal mass was not identified in any of the patients. Two patients undergoing therapy received the hyper-CVAD regimen and had a poor response to early treatment. One of the two was subsequently treated with Campath without success. The 4th patient presented with an isolated chest wall mass. Detailed clinical information is currently unavailable for 2 patients. In all cases, the neoplastic cells were characterized by blastic morphology and coexpression of bilineage lymphoid antigens. The neoplastic cells in 3 cases with systemic disease were immunoreactive with T-cell antigens CD3, CD5, CD7, CD43, and B-cell antigens CD79a and Pax-5; 2/3 cases that had FCM data both showed expression of CD19 and surface γ/δ-TCR, as well as myeloid antigens CD11c and CD33. The case without FCM data lacked βF1 (α/β-TCR) expression by IHC. In addition, 2/3 cases also had immunophenotypic features of typical T-lymphoblastic leukemia or lymphoma (T-ALL) (CD34+ and TdT+). All three cases lacked NK cell antigen CD56 and T-cell antigen CD2, and were double negative for CD4 and CD8. The tumor cells from the 4th case were positive for all pan-T cell antigens (CD2, CD3, CD7, CD43) except CD5 by IHC, and were double negative for CD4 and CD8. These features were phenotypically consistent with a γ/δ-T cell lymphoma, which was also supported by lack of detectable βF1 expression. Similar to other cases, however, these cells were also positive for B cell antigens Pax-5 and CD79a, as well as CD20. The only patient who had successful molecular and cytogenetic analyses had isochromosome 9 and clonal TCR gamma gene rearrangement. In summary, T-cell lymphoma or leukemia with bi-lineage lymphoid antigens is associated with Pax-5 expression, which may account for the upregulation of CD19. It appears to be a rare disease of γ/δ-T-cell origin with a unique phenotypic profile. Further study is needed to determine if the observed i(9) involves disruption of the Pax-5 locus at 9q13.


Science ◽  
1988 ◽  
Vol 239 (4847) ◽  
pp. 1541-1544 ◽  
Author(s):  
S. Hedrick ◽  
I Engel ◽  
D. McElligott ◽  
P. Fink ◽  
M. Hsu ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Dongxu Zhao ◽  
Zhixia Teng ◽  
Yanjuan Li ◽  
Dong Chen

Recently, several anti-inflammatory peptides (AIPs) have been found in the process of the inflammatory response, and these peptides have been used to treat some inflammatory and autoimmune diseases. Therefore, identifying AIPs accurately from a given amino acid sequences is critical for the discovery of novel and efficient anti-inflammatory peptide-based therapeutics and the acceleration of their application in therapy. In this paper, a random forest-based model called iAIPs for identifying AIPs is proposed. First, the original samples were encoded with three feature extraction methods, including g-gap dipeptide composition (GDC), dipeptide deviation from the expected mean (DDE), and amino acid composition (AAC). Second, the optimal feature subset is generated by a two-step feature selection method, in which the feature is ranked by the analysis of variance (ANOVA) method, and the optimal feature subset is generated by the incremental feature selection strategy. Finally, the optimal feature subset is inputted into the random forest classifier, and the identification model is constructed. Experiment results showed that iAIPs achieved an AUC value of 0.822 on an independent test dataset, which indicated that our proposed model has better performance than the existing methods. Furthermore, the extraction of features for peptide sequences provides the basis for evolutionary analysis. The study of peptide identification is helpful to understand the diversity of species and analyze the evolutionary history of species.


2020 ◽  
Vol 599 ◽  
pp. 113747 ◽  
Author(s):  
Phasit Charoenkwan ◽  
Chanin Nantasenamat ◽  
Md Mehedi Hasan ◽  
Watshara Shoombuatong

1990 ◽  
Vol 171 (3) ◽  
pp. 959-964 ◽  
Author(s):  
M D Mossalayi ◽  
J C Lecron ◽  
A H Dalloul ◽  
M Sarfati ◽  
J M Bertho ◽  
...  

The ability of human thymus-derived CD7+CD2-CD3- cells to acquire mature T cell antigens was assessed. Purified CD7+ thymocytes were incubated with rIL-1, rIL-2, and/or recombinant soluble CD23 (rsCD23). Short-term incubation of these cells with only rsCD23 + rIL-1 induced mature T cell antigen expression on at least half of the cells. The induction of CD2 was functionally significant, as these cells became able to respond to CD2 triggering and could proliferate in response to IL-2. Possible sources of CD23 in the thymus are under investigation.


2017 ◽  
Vol 11 (11) ◽  
pp. 868-875
Author(s):  
Yuyang Zhang ◽  
Guangming Zhong ◽  
Huihua Cai ◽  
Siping Chen ◽  
Donghua Sun ◽  
...  

Introduction: Chlamydia trachomatis is the leading cause of sexually transmitted bacterial disease, which may cause significant threats, such as pelvic inflammatory disease and tubal factor infertility, to women if untreated. The pathological mechanisms of chlamydia-induced disease remain largely unknown, but it has been proposed that CPAF, a chlamydia-secreted serine protease, may play major roles in aiding chlamydial infection and contribute to chlamydia pathogenesis during in vivo infection. According to previous results, CPAF targets host immunity by degrading antimicrobial peptides and neutralizing complement activity; however, whether CPAF is involved in chlamydial antigen presentation has never been reported. Methodology: Antigen presentation assay was used to monitor the effects of CPAF on OT1-, OT2-, and chlamydia T cell antigen-mediated antigen presentation. In vitro cell-free degradation assay was used to detect CPAF processing of chlamydia T cell antigens. Results: We found that CPAF preferably inhibits OT2- but not OT1-mediated antigen presentation. CPAF inhibits OT2 antigen presentation by direct proteolytic cleavage in the wild type CPAF, but not enzymatic mutants. Importantly, several previously identified chlamydial T cell antigens were selectively degraded by CPAF when co-incubated in vitro. In addition, specific inhibition T cell antigen presentation by CPAF was correlated with T cell antigen cleavage by CPAF in vitro assay. Conclusions: Our experiments demonstrated that CPAF selectively and specifically degrades chlamydial T cell antigens, which chlamydia may utilize as a novel mechanism for evading host immune responses to promote chlamydia survival.


2012 ◽  
Vol 80 (4) ◽  
pp. 1510-1518 ◽  
Author(s):  
Hong Yu ◽  
Karuna P. Karunakaran ◽  
Xiaozhou Jiang ◽  
Caixia Shen ◽  
Peter Andersen ◽  
...  

ABSTRACTMajor impediments to aChlamydiavaccine lie in discovering T cell antigens and polarizing adjuvants that stimulate protective immunity. We previously reported the discovery of three T cell antigens (PmpG, PmpF, and RplF) via immunoproteomics that elicited protective immunity in the murine genital tract infection model againstChlamydiainfection after adoptive transfer of antigen-pulsed dendritic cells. To expand the T cell antigen repertoire necessary for aChlamydiavaccine, we evaluated 10 newChlamydiaT cell antigens discovered via immunoproteomics in addition to the 3 antigens reported earlier as a molecular subunit vaccine. We first tested five adjuvants, including three cationic liposome formulations (dimethyldioctadecylammonium bromide-monophosphoryl lipid A [DDA-MPL], DDA-trehalose 6,6′-dibehenate [DDA-TDB {CAF01}], and DDA-monomycolyl glycerol [DDA-MMG {CAF04}]), Montanide ISA720–CpG-ODN1826, and alum using the PmpG protein as a model T cell antigen in the mouse genital tract infection model. The results showed that the cationic liposomal adjuvants DDA-MPL and DDA-TDB elicited the best protective immune responses, characterized by multifunctional CD4+T cells coexpressing gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), and reduced infection by more than 3 logs. Using DDA-MPL as an adjuvant, we found that 7 of 13ChlamydiaT cell antigens (PmpG, PmpE, PmpF, Aasf, RplF, TC0420, and TC0825) conferred protection better than or equal to that of the reference vaccine antigen, major outer membrane protein (MOMP). Pools of membrane/secreted proteins, cytoplasmic proteins, and hypothetical proteins were tested individually or in combination. Immunization with combinations protected as well as the best individual protein in that combination. The T cell antigens and adjuvants discovered in this study are of further interest in the development of a molecularly definedChlamydiavaccine.


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