Comorbidity-Guided Text Mining and Omics Pipeline to Identify Candidate Genes and Drugs for Alzheimer's Disease.

Alzheimer's disease (AD), a multifactorial neurodegenerative disorder, is prevalent among the elderly population. It is a complex trait with mutations in multiple genes. Although the US Food and Drug Administration (FDA) has approved a few drugs for AD treatment, a definitive cure remains elusive. Research efforts persist in seeking improved treatment options for AD. Here, a hybrid pipeline is proposed to apply text mining to identify comorbid diseases for AD and an omics approach to identify the common genes between AD and five comorbid diseases-dementia, type 2 diabetes, hypertension, Parkinson's disease, and Down syndrome. We further identified the pathways and drugs for common genes. The rationale behind this approach is rooted in the fact that elderly individuals often receive multiple medications for various comorbid diseases, and an insight into the genes that are common to comorbid diseases may enhance treatment strategies. We identified seven common genes-PSEN1, PSEN2, MAPT, APP, APOE, NOTCH, and HFE-for AD and five comorbid diseases. We investigated the drugs interacting with these common genes using LINCS gene-drug perturbation. Our analysis unveiled several promising candidates, including MG-132 and Masitinib, which exhibit potential efficacy for both AD and its comorbid diseases. The pipeline can be extended to other diseases.

Text Mining Protocol to Retrieve Significant Drug-Gene Interactions from PubMed Abstracts.

Genes and proteins form the basis of all cellular processes and ensure a smooth functioning of the human system. The diseases caused in humans can be either genetic in nature or may be caused due to external factors. Genetic diseases are mainly the result of any anomaly in gene/protein structure or function. This disruption interferes with the normal expression of cellular components. Against external factors, even though the immunogenicity of every individual protects them to a certain extent from infections, they are still susceptible to other disease-causing agents. Understanding the biological pathway/entities that could be targeted by specific drugs is an essential component of drug discovery. The traditional drug target discovery process is time-consuming and practically not feasible. A computational approach could provide speed and efficiency to the method. With the presence of vast biomedical literature, text mining also seems to be an obvious choice which could efficiently aid with other computational methods in identifying drug-gene targets. These could aid in initial stages of reviewing the disease components or can even aid parallel in extracting drug-disease-gene/protein relationships from literature. The present chapter aims at finding drug-gene interactions and how the information could be explored for drug interaction.

A Hybrid Protocol for Finding Novel Gene Targets for Various Diseases Using Microarray Expression Data Analysis and Text Mining.

The advancement in technology for various scientific experiments and the amount of raw data produced from that is enormous, thus giving rise to various subsets of biologists working with genome, proteome, transcriptome, expression, pathway, and so on. This has led to exponential growth in scientific literature which is becoming beyond the means of manual curation and annotation for extracting information of importance. Microarray data are expression data, analysis of which results in a set of up/downregulated lists of genes that are functionally annotated to ascertain the biological meaning of genes. These genes are represented as vocabularies and/or Gene Ontology terms when associated with pathway enrichment analysis need relational and conceptual understanding to a disease. The chapter deals with a hybrid approach we designed for identifying novel drug-disease targets. Microarray data for muscular dystrophy is explored here as an example and text mining approaches are utilized with an aim to identify promisingly novel drug targets. Our main objective is to give a basic overview from a biologist's perspective for whom text mining approaches of data mining and information retrieval is fairly a new concept. The chapter aims to bridge the gap between biologist and computational text miners and bring about unison for a more informative research in a fast and time efficient manner.

Finding Gene Associations by Text Mining and Annotating it with Gene Ontology.

Digitalization of the research articles and their maintenance in a database was the first stage toward the development of biomedical research. With the large amounts of research being published daily, it has created a large gap in accessing all the articles for review to a given problem. To understand any biological process, an insight into the role of each element in the genome is essential. But with this gap in manual curation of literature, there are chances that important biological information may be lost. Hence, text mining plays an important role in bridging this gap and extracting important biological information from the text, finding associations among them and predicting annotations. An annotation may be gene, gene products, gene names, their physical and functional characteristics, and so on. The process of annotations may be classified as structural annotation, functional annotation, and relational annotation. In this chapter, a basic protocol utilizing text mining to extract biological information and predict their functional role based on Gene Ontology is provided.

Extracting Significant Comorbid Diseases from MeSH Index of PubMed.

Text mining is an important research area to be explored in terms of understanding disease associations and have an insight in disease comorbidities. The reason for comorbid occurrence in any patient may be genetic or molecular interference from any other processes. Comorbidity and multimorbidity may be technically different, yet still are inseparable in studies. They have overlapping nature of associations and hence can be integrated for a more rational approach. The association rule generally used to determine comorbidity may also be helpful in novel knowledge prediction or may even serve as an important tool of assessment in surgical cases. Another approach of interest may be to utilize biological vocabulary resources like UMLS/MeSH across a patient health information and analyze the interrelationship between different health conditions. The protocol presented here can be utilized for understanding the disease associations and analyze at an extensive level.

Comparison of newer Kane formula with Sanders Retzlaff Kraff/Theoretical and Barrett Universal II for calculation of intraocular lens power in Indian eyes.

Purpose: To compare the efficacy of Kane formula with Sanders Retzlaff Kraff/Theoretical (SRK/T) and Barrett Universal II in predicting intraocular lens (IOL) power in Indian eyes. Methods: This retrospective study conducted in a tertiary care eye hospital. Data from patients having uneventful cataract surgery with Tecnis ZCB00 IOL implantation were obtained from Lenstar and electronic medical records. Eyes were divided into subgroups based on axial length (AL) as short (<22.0 mm), medium (22-24 mm), and long (>24 mm). The predicted refractive outcome for each patient was calculated after optimizing the lens constant. Prediction error was calculated by subtracting the predicted spherical equivalent from achieved spherical equivalent 1 week post-surgery. The mean absolute error (MAE) and median absolute error (MedAE) and percentage of eyes within 0.25, 0.5, 1, and 2 D were calculated for each formula. Friedman test, Cochrane Q test were used for statistical analysis. Results: Out of the 350 eyes included in the study, we found that without lens constant optimization, Barrett formula performed better than SRK/T and Kane (P < 0.0001). Over the entire range of axial lengths, Kane formula performed slightly inferior compared to Barrett and SRK-T, both of which performed equally well (P = 0.006). On subgroup analysis, Kane formula performed inferiorly for medium eyes as compared to the other two. No significant differences were noted between the formulae for short and long eyes. Conclusion: Kane formula did not outperform Barrett Universal II and SRK/T in Indian eyes.