Computing Skin Cutaneous Melanoma Outcome From the HLA-Alleles and Clinical Characteristics

Dhall, Anjali; Patiyal, Sumeet; Kaur, Harpreet; Bhalla, Sherry; Arora, Chakit; Raghava, Gajendra P. S.

doi:10.3389/fgene.2020.00221

Cited by 41 publications

(27 citation statements)

References 75 publications

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“…There are also many important studies involved in the prognosis of SKCM. Anjali et al developed a webserver to predict the survival of SKCM patients ( Dhall et al, 2020 ). Li et al also predicted the metastatic progression of melanoma based on mRNA expression status ( Li et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

m6A-Related lncRNAs Are Potential Biomarkers for the Prognosis of Metastatic Skin Cutaneous Melanoma

Huang

Lyu

Gao

et al. 2021

Front. Mol. Biosci.

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Background: The incidence of skin cutaneous melanoma (SKCM) has risen more rapidly than any other solid tumor in the past few decades. The median survival for metastatic melanoma is only six to nine months and the 5°years survival rate of patients with conventional therapy is less than 5%. Our aim was to reveal the potential molecular mechanism in m6A modification of lncRNA and provide candidate prognostic biomarkers for metastatic SKCM.Methods: lncRNAs expression level was obtained by re-annotation in TCGA and CCLE datasets. m6A-related lncRNAs were selected though correlation analysis. Univariate cox regression analysis was used to screen out independent prognostic factors. LASSO Cox regression was performed to construct an m6A-related lncRNA model (m6A-LncM). Univariate survival analysis and ROC curve were used to assess the prognostic efficacy of this model and candidate lncRNAs. Enrichment analysis was used to explore the candidate genes’ functions.Results: We obtained 1,086 common m6A-related lncRNAs after Pearson correlation analysis in both two datasets. 130 out of the 1,086 lncRNAs are independent prognostic factors. 24 crucial lncRNAs were filtered after LASSO Cox regression analysis. All the m6A-LncM and the 24 lncRNAs were related to overall survival. Stratified survival analysis of m6A-LncM showed that the model retains its prognostic efficacy in recurrence, radiation therapy and other subgroups. Enrichment analysis also found that these lncRNAs were immune associated.Conclusion: Here, we obtained 24 crucial lncRNAs that may be potential biomarkers to predict survival of metastatic SKCM and may provide a new insight to improve the prognosis of it.

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Section: Discussionmentioning

confidence: 99%

m6A-Related lncRNAs Are Potential Biomarkers for the Prognosis of Metastatic Skin Cutaneous Melanoma

Huang

Lyu

Gao

et al. 2021

Front. Mol. Biosci.

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“…73 IL-6 inducing and 598 non-IL-6 inducing peptides) was used for external validation. Then, we implement standard 5-fold cross-validation evaluation techniques, which is frequently used in the previous studies [ 51 , 52 ]. Firstly, the entire training dataset is divided into five equivalent sets or folds, with all the 5-folds have the same number of positive and negative examples.…”

Section: Methodsmentioning

confidence: 99%

Computer-aided prediction and design of IL-6 inducing peptides: IL-6 plays a crucial role in COVID-19

Dhall

Patiyal

Sharma

et al. 2020

Briefings in Bioinformatics

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102

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Interleukin 6 (IL-6) is a pro-inflammatory cytokine that stimulates acute phase responses, hematopoiesis and specific immune reactions. Recently, it was found that the IL-6 plays a vital role in the progression of COVID-19, which is responsible for the high mortality rate. In order to facilitate the scientific community to fight against COVID-19, we have developed a method for predicting IL-6 inducing peptides/epitopes. The models were trained and tested on experimentally validated 365 IL-6 inducing and 2991 non-inducing peptides extracted from the immune epitope database. Initially, 9149 features of each peptide were computed using Pfeature, which were reduced to 186 features using the SVC-L1 technique. These features were ranked based on their classification ability, and the top 10 features were used for developing prediction models. A wide range of machine learning techniques has been deployed to develop models. Random Forest-based model achieves a maximum AUROC of 0.84 and 0.83 on training and independent validation dataset, respectively. We have also identified IL-6 inducing peptides in different proteins of SARS-CoV-2, using our best models to design vaccine against COVID-19. A web server named as IL-6Pred and a standalone package has been developed for predicting, designing and screening of IL-6 inducing peptides (https://webs.iiitd.edu.in/raghava/il6pred/).

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“…As mentioned, the circumstantial association with melanoma (i.e., a ‘hyper’ anti-melanoma response) has sparked interest for this theory, but lacks evidence for any causal relation ( 109 ). Remarkably, although HLA-A29 can effectively present melanoma epitopes ( 1 ), HLA-A29 is associated with worse survival compared to HLA-A29-negative melanoma patients ( 110 ). This could indicate that perhaps similar to the effects of ERAP2, in general, HLA-A29 and ERAP2 may ‘lower’ the immunogenic peptide cargo presented to T cells, but only increase the expression of a very limited (perhaps single) antigen under specific conditions that cause BU.…”

Section: Hla-a29 and Autoantigen Presentationmentioning

confidence: 99%

HLA-A29 and Birdshot Uveitis: Further Down the Rabbit Hole

Kuiper

Venema

2020

Front. Immunol.

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HLA class I alleles constitute established risk factors for non-infectious uveitis and preemptive genotyping of HLA class I alleles is standard practice in the diagnostic work-up. The HLA-A29 serotype is indispensable to Birdshot Uveitis (BU) and renders this enigmatic eye condition a unique model to better understand how the antigen processing and presentation machinery contributes to non-infectious uveitis or chronic inflammatory conditions in general. This review will discuss salient points regarding the protein structure of HLA-A29 and how key amino acid positions impact the peptide binding preference and interaction with T cells. We discuss to what extent the risk genes ERAP1 and ERAP2 uniquely affect HLA-A29 and how the discovery of a HLA-A29-specific submotif may impact autoantigen discovery. We further provide a compelling argument to solve the long-standing question why BU only affects HLA-A29-positive individuals from Western-European ancestry by exploiting data from the 1000 Genomes Project. We combine novel insights from structural and immunopeptidomic studies and discuss the functional implications of genetic associations across the HLA class I antigen presentation pathway to refine the etiological basis of Birdshot Uveitis.

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Computing Skin Cutaneous Melanoma Outcome From the HLA-Alleles and Clinical Characteristics

Cited by 41 publications

References 75 publications

m6A-Related lncRNAs Are Potential Biomarkers for the Prognosis of Metastatic Skin Cutaneous Melanoma

m6A-Related lncRNAs Are Potential Biomarkers for the Prognosis of Metastatic Skin Cutaneous Melanoma

Computer-aided prediction and design of IL-6 inducing peptides: IL-6 plays a crucial role in COVID-19

HLA-A29 and Birdshot Uveitis: Further Down the Rabbit Hole

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