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Next Generation Sequencing: An Illumina for clinical research

By Neha Shinde, Lead, Data Management at Biorasi

When it comes to drug treatment for patients, “the cookie-cutter approach” can be a bit dubious, as each individual has varying responses to the same drug. Specifically, the vulnerability of adverse reactions to the drug is often the most common of responses. The main pathology of any disease directly or indirectly revolves around the genetic factors and ,therefore, pharmacogenomics – the study of how genes affect drug response – works conjointly to predict the efficacy of the drug. One of the key drivers that has transformed both the molecular and diagnostic areas of pharmacogenomics is Next Generation Sequencing (NGS). With the aim of clinical trials to capture the maximum amount of data for the drug, NGS technology allows to scientists connect the dots about the missing data and provide detailed descriptions concerning genomic landscapes.

Conventional sequencing methods involve Sanger sequencing technology, which has been effective for sequencing a short DNA fragments. However, the need for larger sequence fragments has led to Next Generation Sequencing (NGS). NGS technology determines and analyzes multiple DNA or RNA sequences to study focusing on the differences in DNA among individuals or the differences between populations (genetic variations) associated with diseases or other biological phenomena. As NGS enables cross-examination of multiple genes at one time in varied samples, it not only facilitates agility but is also cost-effective. Hence, this technology could have major implications on genomic and clinical research and also be used across reproductive health, agricultural science, and forensic science.

Eighty percent of rare diseases have identified genetic origins, and risky delays or ambiguous diagnoses may lead to inaccurate treatments. Technologies like NGS can assist in early prognosis and diagnosis ensuring the safety of the patient. The basis for drug effectiveness is to imitate the gene function which has been mutated. Using the NGS technology, research can be conducted to identify the target genes and impersonate them.

The most important marker of any clinical trial is the screening to determine the eligibility of the patient as there are multiple complexities and criteria associated with the trials. NGS can act as a guide in such cases, helping to allocate patients to specific clinical trials especially if the trial is targeting genomic profiling. If patients with specific genotypes are grouped, the probability of them responding to the treatment in similar manner increases eventually providing analogous results for the study. This will have a significant impact on the sample size of the trial, too. Histological data does provide predefined information, however, looking at the array of permutations, it indeed is not enough for characterizing treatment options. Technologies like NGS can be used during the early recruitment stages or later dosing stages to optimize enrolment or dosing based on genomic profiling. Another approach to maximize the potential benefit of a clinical trial is targeted drug combinations that are approved. However, this approach needs technology like NGS for genetic and molecular profiling.

NGS enables analyzation of multiple genes at once. This is associated with large database management to store the clinical information efficiently. This facilitates the meta-analysis wherein the existing verified data can be linked to derive better conclusions from the trial and to check if the drug has any effects on other diseases as well. Decentralized strategies can also be built up using the preexisting data with such technologies, which will help to perform predictive analysis. This provides an integration of information among the different therapeutic areas and leads to a decision on the appropriate treatment.

NGS technology offers numerous solutions, from congregating different drugs with the same/varied effects to streamlining the clinical trials through the understanding of the genetic basis. In the future, it may also facilitate customized therapies ranging from precision medicine and metagenomics to the discovery of new pathogens and virulence factors-moving beyond the cookie cutter approach into further customization of treatment for patients.