EyeTFDB: a Curated Eye Disease Transcription Factor Web-Based Platform

Background:  The TFs identify as distinct DNA sequences to regulate transcription processes and chromatin forming.   Materials and Methods: To address needs in multiple areas, we present the EyeTFDB (https://eyetfdb.databanks.behrc.ir/) web-based platform, a novel platform of curated data. It combines the eye disease-related pathways data from the KEGG and REACTOME and their associated mRNAs. Furthermore, we expanded our mRNAs data by extracting disease-related data from valuable databases like DisGeNET and OMIM.   Results: Despite the high importance of eye diseases and the global need for further research in this area, still, there is no remarkable comprehensive database for transcription factors of eye diseases. Here we integrated multiple heterogeneous datasets from different databases addressing this need. We collected 429 mRNAs from 1258 pathways for 25 types of eye disease. In addition, transcription factors are separated from this considerable amount of data.  EyeTFDB user interface is designed to facilitate multiple types of the desired use: (i) the interactive investigations of individual entries on the level of a gene, transcription factor, pathway, eye disease, and (ii) the construction of highly customized datasets using advanced searching and filtering. Conclusion: The status of eye TFs and their broad interactions could significantly influence eye health. EyeTFDB, as well as other established databases serve as rich resources for assisting the researchers in exploring eye TFs in the elevation of public health. The wealthy information generated from future investigations can be incorporated into EyeTFDB for better serving the eye TF research and exploration efforts

EyeMirDB: a Web-Based Platform of Experimentally Supported Eye Disease-miRNA Information

Background:  Studies of microRNA biology have increased in numerous scientific research domains, including eye science. MicroRNAs (miRNAs) are small non-coding RNAs that operate as post-transcriptional regulators of gene expression by destroying or blocking the translation of target messenger RNA.   Despite significant efforts to investigate the miRNA of eye disease, a complete platform of frequent ocular disease with genes, pathways, and miRNA is still unavailable. Material and Methods: Three well-known databases were used as the main data source: DisGeNET, OMIM, and KEGG. The curated genes involved in each disease were manually collected. Then, the annotation information like gene’s sequence, description, chromosome’s number, start and end loci were extracted from the Ensembl data source. Gene’s pathway information was earned from KEGG and Reactome. Finally, experimentally validated gene’s related miRNA has been collected from miRecords, miRTarBase, and TarBase. In order to consider miRNAs expression in ocular tissues. Results: we present EyeMirDB (http://eyemirdb.databanks.behrc.ir/), a web-based platform of consisting of all predicted and validated miRNAs. Information on the annotation of miRNA-related genes was also collected in order to better understand the effects of miRNA. Pathways by which these genes are active were also identified. Right now, EyeMirDB contains 429 curated genes, 1258 pathways, and 2596 validated miRNAs of 25 prevalent ocular diseases. Conclusion: We introduce EyeMirDB, a web-based platform of Eye diseases-related interactions including disease-gene, gene-miRNA, gene-pathway curated information, and annotations, with the optionality of studying all these entities from different viewpoints. This data portal is a good entry point for ocular disease researchers

Proliferative Diabetic Retinopathy from a Network Biology Perspective

Background: Proliferative Diabetic Retinopathy (PDR) is the advanced version of Diabetic Retinopathy in which, new, fragile blood vessels can start to develop in the retina and into the vitreous, the gel-like fluid that fills the back of the eye.Material and Methods: Here we study PDR from a whole system viewpoint in which network science is utilized for the system representation. Our objective is to explore the role of differentially expressed genes in the development of PDR. For this purpose, we have designed a framework in which the genes with high differential expression are identified and their PPI networks are regenerated. Next, influential dominating nodes are specified in the resulting network. With the enrichment analyses, the output set is validated and its role in the PDR is studied.Results: These results suggest that the output gene set has a significant association with the disease of study. Additionally, we identify miRNAs regulating the transcription of genes inside the explored module as biomarkers affecting the progress of PDR.Keywords: Diabetic Retinopathy; Network; Systems Biology; Differential Gene Expression

EyeLncDB: A curated database of human long non-coding RNAs related to eye diseases

Background: Eye diseases (EDs) are disorders of the ocular system, causing visual damage and sightlessness. Different studies have specified a wide range of biological functions of LncRNAs; consequently, their dysfunction directs to several diseases such as EDs. Growing evidence suggests that LncRNAs might be a new class of molecules for disease diagnosis and treatment in the future. Due to the importance and the detection of a large number of LncRNAs, genome-wide analyses are essential to identify which LncRNAs are associated with different diseases. For this purpose, it is vital to collect experimentally validated LncRNAs and predict novel LncRNAs associated with various eye diseases in a systematic manner. Material and methods: In the present study, researchers attempted to expand the current data using a powerful bioinformatics pipeline. We integrated the different resources of eye-related LncRNA information to provide a customized entry point for LncRNA-target research. Results: As a result, 429 mRNAs related to 25 humans EDs were identified, and 151 new experimentally validated physical interactions associated with these mRNA were identified. Finally, after organizing all the identified LncRNAs, respectively, 1038 and 89 experimentally validated and predicted LncRNAs were obtained. Conclusion: Here, we propose EyeLncDB (http://eyelncedb.databanks.behrc.ir/), a web-based platform of eye-related validated LncRNA data that contains the mentioned integrated information. EyeLncDB provides information on LncRNA-related diseases, pathways, genes, and targets with external links to the original data sources

Transcriptomic Analysis of Human Retina Reveals Molecular Mechanisms Underlying Diabetic Retinopathy in Sexually Divergent Manner

Today, retinopathy is one of the major causes of vision loss. With the increasing prevalence of obesity, diabetes, blood fat, and hypertension, the number of patients with retinopathy is increasing. Gender is an important factor in a variety of retinal diseases but has rarely been studied in clinical and biological studies. The current understanding of the effect of gender on molecular changes and pathways involved in the onset and progression of diabetic retinopathy (DR) is limited. The aim of this study is to investigate the differences in Diabetic patients’ retinal gene expression between the two sexes. Through RNAseq analysis, mRNA expression profiles were analyzed from 40 post-mortem samples from 20 patients with diabetic macular edema (DME) stage of DR. 29 of samples were female and 11 were male. So our groups were control-female, DME-female, control-male and, DME-male. Human retinal single-cell RNA‑Sequencing data revealed 245 differently expressed genes in female-DME and male-DME patients. The results of enrichment analysis show that most up-regulated genes take part in pathways involved in Osteoclast-associated receptor (OSCAR) binds collagen and Surfactant protein D (SP-D), apoptosis, and tyrosine metabolism molecular functions. In this study, we detected a significant association between tyrosine metabolism and diabetic retinopathy in the DME stage. The increased DR risk was observed only in female patients with the abnormality of low tyrosine metabolism. Furthermore, we found a significant interaction between DR and the coexistence of low tyrosine metabolism. Suggesting that control of tyrosine metabolism might confer great risk reduction for DR in female patients

Differential Expression of Genes in the Cornea compared to the Optic Nerve

AbstractBackground: Identification of tissue-specific biomarkers can help us in finding the causes of disease. In this context, finding genes that are expressed in different tissues gives us guidance in cell differentiation.Material and Methods: we examined genes with different expressions in both optic nerve and corneal tissues. First, we found differentially expressed genes on a dataset including 4 corneal and 4 optic nerve samples, then evaluated them on another independent dataset to validate the findings. Finally, we performed Enrichment Analysis and Network Evaluation of the obtained DEGs.Results: we gained 6 genes that are highly expressed in the optic nerve than the cornea and 99 genes with higher expression in the cornea than in the optic nerve.Conclusion: We saw traces of DEGs in the mechanism of action of the corresponding cells. In this study, we did not use the FDR method and thus we do not have false positive in final DEGs.Keywords: Biomarker Discovery; Cornea; Optic Nerve; Differential Gene Expression Analysis