Growing significance of molecular diagnostics

Molecular testing could potentially revolutionize the testing and monitoring of remotely-situated populations and cover a larger number of the population by employing fewer resources, writes Dr. Angeli Misra, Director, Lifeline Laboratory

About Author: Dr. Angeli Misra is Director, Lifeline Laboratory – one of the premier advanced pathology laboratories of Delhi-NCR region. She brings with her an enormous experience of technical and service expertise spanning over 34 years in clinical pathology. Having completed her MBBS from Nagpur University, Dr. Misra completed her MD in Pathology with a gold medal from the All Indian Institute of Medical Sciences, New Delhi. Her research works include contributions to Eli-Lilly Company; Zydus Byk Healthcare Ltd.; and L.G Life Sciences.

Molecular diagnostics is the study of body fluids by a combination of laboratory medicine, technology, and molecular genetics to assess a person’s health at the cellular and molecular level, by genomic analyzing bio markers for genetic alterations in the genetic sequencing of DNA (deoxyribonucleic acid), RNA (ribonucleic acid) and amino acids (proteins) and their interaction and activity inside the cells in the blood, urine or synovial fluid, for the identification and assessment of the genetic basis of inherited diseases like cancer. Various combined techniques which are powerful and highly-sensitive, are employed to identify the pattern in which the DNA and RNA of an infection (bacterial, fungal, viral or parasitic) expresses, and the body’s response to them, to study the mechanism of a disease, to determine the disease predisposition of a person and to make an accurate diagnosis in order to design and customize therapeutic treatment modalities.
PCR technology was first introduced in the world in 1949, with Linus Pauling et al, when he characterized sickle cell anemia as a molecular disease. However, it was decades before molecular biology was established as a scientific discipline and became usable in labs as a crucial diagnostic tool for disease diagnostics. Thereafter, genome sequencing and cDNA cloning firmly established itself as an essential diagnostic tool, and in 1976, Kan et al became the first to make a pre-natal diagnosis of alpha- thalassemia by employing MDx technique. This laid the foundation for the use of this technology to characterize genetic diseases as well as the genetic characterization of infectious diseases. The golden period of MDx technique thus began in the 1980’s, when it was accepted in the world of laboratory medicine, as PCR technology was able to detect and diagnose gene mutation within hours. Based on this gene amplification, the development of sophisticated and sensitive design methods of many variant detection schemes became possible, and DNA sequencing became the gold standard for the identification and assessment of pathogens.
PCR technology has, in effect, shown the path forward for the future as a fantastic and highly sensitive quality diagnostic technique, as it is accurate, precise and gives quick results.
Genome sequencing is certainly a huge leap forward. In the coming years, low-resource molecular diagnostics will feature prominently on the diagnostics map of the world, along with ancillary services like bio-safety and supply chain management, bio-engineering and quality assurance.
The current Covid-19 pandemic scenario has brought the significance of molecular diagnostics into sharp focus. The diagnostic industry market is expanding in leaps and bounds, and the laboratory equipment manufacturing industry too has experienced a tremendous boost, inviting FDI and promoting extensive research. There has been a gigantic leap in the diagnostic market worldwide, as well as in India.
An effective life-saving tool for preventive healthcare management, genetic tests carried out on blood, skin tissue, hair, urine, synovial fluid or other tissue can predict the risk of diseases like cancer and heart disease. Genetic mutations and disorders which cause many diseases can be predicted long before any symptoms manifest. On the basis of these tests, timely medical intervention and other preventive treatment measures can be taken.
PCR- techniques require only a fragment of the infectious agents for rapid analyses and early diagnosis, in comparison to conventional culture-based methods. Besides that, infectious agents detected by multiplex panels may include bacteria, fungi, and parasites as well as viruses like herpes, HPV, HIV, etc. ELISA is a popular, cost-effective diagnostic test for the quantification of a specific protein.
Although synovial fluid sample relatively more difficult to obtain than a blood sample, it is more advantageous due to its increased potential for accuracy and may well be the best method for diagnosis.
An important aspect of PCR (polymerase chain reaction)-based technique is that it helps to determine drug resistance too.
Metabolomics, another aspect of molecular pathology, is the scientific study of chemical processes involving metabolites. It is being touted as a potential and powerful tool for the diagnosis and application of molecular techniques to design clinical therapy in the fields of orthopedics and joint surgery.
The use of nucleic acid analysis has been most successful in the setting of treatment of chronic wounds among diabetic patients.
Latest molecular testing methods are more cost-effective as compared to traditional culture-based clinical microbiology testing methods. In spite of their seemingly high expense, they are flexible enough to pivot rapidly to new threats: e. g. Ebola and Yellow fever hemorrhagic viruses in Nigeria were rapidly detected using molecular methods of rapid PCR test weeks before more standard reference techniques could be deployed). Another case in point is that of Bangladesh were molecular methods increased pathogen identification in patients with meningitis several times more, trebled the conventional sensitivity and retrospectively uncovered a chikungunya virus outbreak. DNA-based tests helped identify typhoid-centric hot spots, and successfully accomplish the polio eradication program. Genexpert helped detect tuberculosis at low cost – similarly, analogues methods can be used for detecting cholera, Sars-CoV-2, and other enteric viruses.
In resource-limited settings, molecular equipment was commonly reserved for special or reference-only testing, but local production of testing materials has proved to be commercially viable in the low-income countries that need them the most. Molecular testing could potentially revolutionize the testing and monitoring of remotely-situated populations and cover a larger number of the population by employing fewer resources. They are also more in-depth, specific and accurate, with rapid turnaround time, helping medical experts to take informed decisions regarding treatment and therapy modalities.
On the downside, not every path lab has the infrastructure to provide molecular diagnostic facilities, but this only goes on to show the tremendous potential waiting to be tapped for their individual growth. Also, imparting training of technicians in PCR technology skills holds enormous possibilities.