The Changing Landscape Of Molecular Diagnostics

The coming era will be revolutionary; it is not only going to change diagnostic systems but also treatment and therapy.

The healthcare system is critically and crucially dependent upon diagnostics. Today’s medical decision making is strongly based upon the diagnostics results. Right from the genetic tests that can help notify personalized cancer treatment to the microbial culture for recognition of the right antibiotic combating an infection, diagnostics provide critical insights at every stage of medical care prevention, detection, diagnosis, treatment, and successful management of health conditions.

Molecular diagnostics has transformed diagnostics dynamically, leading to insights in research and treatment in many disease states that are revolutionizing healthcare. Unfailing prognosis of a broad range of infectious diseases such as hepatitis and HIV and the swelling demand for biomarkers for conducting rapid diagnosis have been anticipated to be key for the growth of the world molecular diagnostics market. One of the important factors expected to boost market growth could be the increasing research and development investment in biomarkers observed in several emerging as well as developed nations.

The global molecular diagnostics market is expected to reach USD 11.54 billion by 2023 from USD 7.71 billion in 2018, at a CAGR of 8.4 percent, estimates MarketsandMarkets. The high prevalence of infectious diseases and various types of cancers, increasing awareness and acceptance of personalized medicine and companion diagnostics, growth in the biomarker identification market, and advancements in molecular techniques are some of the key factors driving the growth of this market.

In recent years, there has been an escalating occurrence of STIs such as those caused by Chlamydia trachomatis and Neisseria gonorrhoeae, which called for an equally frequent need of tests to diagnose them. Thus, the demand for molecular diagnostics has stayed decent since the past few years. The uptake of molecular diagnostics has been envisaged to be bolstered by the ease of operation and convenience offered to clinicians. Furthermore, biomarker advancements have significantly decreased the computational time of usual multiplexed platforms.

The revenue growth of the international molecular diagnostics market has been prognosticated to be hampered by prolonged approvals required from the FDA and other regulatory authorities. This has created a dearth of sophisticated molecular diagnostics tools for clinicians to treat chronic diseases and infections. Moreover, lack of promising reimbursement policies has been projected to discourage the adoption of molecular diagnostics.

However, the demand for molecular diagnostics has been prophesied to gain strength on the back of the rising prominence of personalized therapies in several developed countries. Additionally, the surging requirement of customized healthcare in developed regions could increase the demand in the coming years. The uptake of molecular diagnostics platforms in point-of-care settings could help expose lucrative avenues in the near future.

Technology trends

Post the human genome draft publication, the major challenge, was to improve the existing mutation detection technologies to achieve robust cost-effective, rapid, and high-throughput analysis of genomic variation. In the last decade, technology has improved rapidly and new mutation-detection techniques have become available, whereas old methodologies have evolved to fit into the increasing demand for automated and high-throughput screening. Denaturating high performance liquid chromatography (DHPLC) used for detection of polymorphic changes of disease-causing mutations is one of the new technologies that emerged. It detects the presence of a genetic variation by the differential retention of homo- and heteroduplex DNA on reversed-phase chromatography under partial denaturation. DHPLC has proved to be one of the most powerful tools of mutation detection and is capable of detecting single-base substitutions, deletions, and insertions that can be detected successfully by UV or fluorescence monitoring within 2-3 min in unpurified PCR products as large as 1.5-kilo bases.

Another useful technique of mutation analysis is Pyro sequencing, which is a non-gel-based genotyping technology, and provides a very reliable method and an attractive alternative to DHPLC. Pyrosequencing detects de novo incorporation of nucleotides based on the specific template, causing release of a pyrophosphate, which is converted to ATP and followed by luciferase stimulation. The light produced, detected by a charge couple device camera, is translated to a pyrogram, from which the nucleotide sequence can be deducted.

There has been a steady increase in the number of samples being sent for molecular analysis. This is due to sensitive and robust techniques like real-time PCR and high-throughput techniques like microarray. Among the various molecular techniques discussed above, the use of the PCR in molecular diagnostics is considered the gold standard for detecting nucleic acids and it has become an essential tool in the research laboratory. There is a wider acceptance for real-time PCR due to its improved rapidity, sensitivity, and reproducibility. There is a real-time detection of the PCR product during the exponential phase of the reaction, thereby combining amplification and detection in one single step. The reduced number of cycles, use of fluorogenic labels, and sensitive methods of their detection has largely removed post-PCR detection procedures, making the technique sensitive. Currently, newborns can be screened for phenylketonuria and other treatable genetic diseases.

In the future, one might see children at high risk for coronary artery disease getting characterized and treated to prevent changes in their vascular walls during early adulthood. In the near future, one could witness as a part of standard medical practice, the individual drug monitoring response profiles throughout life, using genetic testing for the identification of their individual DNA signature. Shortly, genetic testing will comprise a wide spectrum of different analyses with a host of consequences for individuals and their families, which is worth emphasizing when explaining molecular diagnostics to the public.

Way forward

In the upcoming years, molecular diagnostics will continue to be of critical importance to public health worldwide. Molecular diagnostic offers physicians with critical information based on the early exploration of pathogens and subtle changes in patients’ genes and chromosomes, allowing for earlier diagnosis, selection of appropriate therapies, and monitoring of disease progression. A wide range of molecular-based tests is available to evaluate DNA difference and changes in gene expression of patient DNA and RNA through real-time PCR, FISH, and sequencing technologies. Further, the complex relationship between diseases like fertility and obesity or metabolic syndrome with cancer have also gained momentum due to exploration of common pathways, that only become possible due to such advancement in molecular techniques.

However, there are many obstacles to overcome before the execution of these tests in clinical laboratories, such as which test to employ, the choice of technology and equipment, and issues such as cost-effectiveness, accuracy, reproducibility, that is robustness and personnel training. Currently PCR-based testing outweighs; however, alternative technologies aimed to explore genome complexity without PCR are anticipated to gain momentum in the coming years as sequencing devices are costlier at present. Furthermore, development of integrated silicon chips mounted with biomolecules is now going to change the concept of a traditional wet lab to lab-on-a-chip. It would be possible to analyze thousands of genes/proteins in hours from a low amount/single cell sample. Thus, coming era will be revolutionary, it will not change diagnostic systems but also plan of treatment and therapy.