diseases attained by numerous computational approaches and drugs with previous
functional indication.
5.3.1
Linking Target Genes to Clinically Approved Drugs
With the rapid rise of technology, there have been significant upgrades in the study
of human genetics and usage of the output data. Many different programs now exist
to capture genetic information and analytical tools to identify key genetic risk factors
(Bush and Moore 2012). Forming a link between disease traits such as disease-
causing genes and clinically approved drugs provides a greater chance of DR success
as compared to a proposed repositioning with no link to a genetic target (Nelson et al.
2015). Transcriptional data reflect gene regulation profiles of human cells in
responses to disease, toxins, drugs, and more. Such data provides closer insight to
specific isolated situations, thus enhancing the understanding of relationships
between the host, drug, and disease (Iorio et al. 2013). The regulation of specific
genes or disease markers may serve as a basis for successful DR. Inhibitors,
stimulators, or other types of approved drugs may be used to specifically counter
the disease-causing effects by moderating those responses.
5.3.2
Usage of Computational Methods
Modern in silico research for DR employs a combination of databases, software, and
analysis tools to elucidate specific and theoretically functional annotations to serve
as targets or potential therapies (Talevi 2018). With the large amount of information
being gathered from genetic studies, it is important to highlight that no particular
stringency of computational workflow suits all. Rather, fluidity in research method-
ology is dependent on factors such as the analysis required to determine disease-
causing gene variants known as causal genes, data availability of known pathways
related to the gene/disease, and the choice of databases and software. Selecting the
most suitable workflow for computational methods can narrow down the search time
and provide more reliable drug candidates for other diseases.
5.3.2.1 Genome-Wide Association Studies (GWAS)
As the role of genetics in medicine has become more evident in the past years, DR
against specific targets using computational approaches have also grown in popular-
ity. A genome-wide association study (GWAS) is a research approach involving the
evaluation and scanning of genomic profiles of different individuals to identify
genetic markers or specific genetic variations that may be associated with a particular
disease (Genome 2021). Gene variation in GWAS is identified from single-
nucleotide polymorphisms (SNPs) of ill individuals. In the past, the clinical applica-
tion of GWAS was criticized as being limited due to the large number of non-coding
gene variants available in the data set. As an implication, when considered for certain
treatments, they may have reduced potential as efficient targets (Pritchard et al.
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