Benefits of Molecular diagnostics

Prenatal

Traditional prenatal testing for chromosomal abnormalities such as Down syndrome relies on analyzing the number and appearance of chromosomes the karyotype.Molecular diagnostic tests such as microarray comparative genomic hybridization instead test DNA samples, which may be less invasive due to the absence of cellular DNA in plasma, but as of 2013 it remains an adjunct to traditional testing.

Treatment

A few single nucleotide polymorphisms in patients tiny differences in their DNA can help predict how quickly they metabolize a particular drug; this is called pharmacogenomics.For example, the CYP2C19 enzyme metabolizes several drugs, such as the anticoagulant clopidogrel, into their active forms.Some patients have polymorphisms at specific positions in the 2C19 gene that cause poor metabolism of these drugs; doctors can test for these polymorphisms and determine whether the drug is fully effective in that patient.Advances in molecular biology have helped to show that some syndromes previously classified as single disorders are actually multiple subtypes with entirely different causes and treatments.Molecular diagnostics can help diagnose subtypes (such as infections and cancers) or genetic analysis of diseases with a genetic component, such as Silver-Russell syndrome.

Infectious disease 

Molecular diagnostics are used to identify infectious diseases such as chlamydia influenza virus and tuberculosis or specific strains such as H1N1 virus or SARS-CoV-2.Gene identification can be rapid; for example, loop-mediated isothermal amplification assays can diagnose malaria parasites and are robust enough for developing countries.But despite these advances in genomic analysis, in 2013, infections were still more often identified by other means their proteome, phage, or chromatographic profiles.Molecular diagnostics are also used to understand a particular strain of a pathogen for example by detecting which resistance genes it possesses and thus which treatments to avoid.Furthermore, metagenomic next-generation sequencing-based analyzes can be implemented to unbiasedly identify pathogenic organisms.

Disease risk management

A patient's genome may contain inherited or random mutations that affect the likelihood of developing the disease in the future.For example, Lynch syndrome is a genetic disorder that predisposes patients to colorectal and other cancers; early detection can lead to close monitoring, which improves patients' chances of a good outcome.Cardiovascular risk is indicated by biomarkers, and screening can measure a child's risk of being born with a genetic disorder such as cystic fibrosis.Genetic testing is ethically complex: patients may not want to take the pressure of knowing their risks.In countries without universal healthcare, known risks may drive up insurance premiums.

Cancer

Cancer is a change in cellular processes that leads to the uncontrolled growth of tumors.Cancer cells sometimes harbor mutations in oncogenes such as KRAS and CTNNB1 (beta-catenin).Analyzing the molecular signatures of cancer cells DNA and its expression levels through messenger RNA allows physicians to characterize cancer and choose the best treatment for their patients.As of 2010, assays that combine a panel of antibodies against specific protein marker molecules are an emerging technology; these multiplex assays promise to measure many markers simultaneously.Other potential future biomarkers include microRNA molecules, which cancer cells express more than healthy cells.Cancer is a constantly evolving disease with a plethora of molecular causes. Disease heterogeneity exists even within individuals.Molecular studies of cancer have demonstrated the importance of driver mutations in tumor growth and metastasis.Many techniques for detecting sequence variation have been developed for use in cancer research.These techniques can generally be grouped into three approaches: polymerase chain reaction (PCR), hybridization, and next-generation sequencing (NGS).Currently, a number of PCR and hybridization assays have been approved by the FDA for in vitro diagnostic use.However, NGS testing is still in the early stages of clinical diagnosis.

An important issue in molecular diagnostic testing for cancer is the detection of DNA sequence variants.Tumor biopsies used for diagnosis consistently contained as little as 5% of the variant of interest compared to wild-type sequences. Furthermore, for non-invasive application in peripheral blood or urine, DNA testing must be specific enough to detect mutations with a variant allele frequency below 0.1%. [twenty two].Currently, by optimizing conventional PCR, there is a new invention, the Amplified Refractory Mutation System (ARMS), a method for detecting DNA sequence variations in cancer.The principle behind ARMS is that the enzymatic extension activity of DNA polymerases is highly sensitive to mismatches near the 3' end of the primer.Many different companies have developed diagnostic tests based on ARMS PCR primers. For example, Qiagen therascreen, Roche cobas [49] and Biomerieux THxID [50] developed FDA-approved PCR tests for the detection of lung, colon, and metastatic melanoma mutations in the KRAS, EGFR, and BRAF genes.Their IVD kits are essentially validated on genomic DNA extracted from FFPE tissue.There are also microarrays that use the hybridization mechanism to diagnose cancer. Using Affymetrix's gene chip technology, more than one million different probes can be synthesized on the array with a detection limit of 1 to 10 mRNA copies per well.Optimized microarrays are generally considered to yield reproducible relative quantification of different targets.Currently, the FDA has approved some diagnostic assays using microarrays: Agendia’s MammaPrint assay can inform breast cancer recurrence risk by analyzing the expression of 70 genes associated with breast cancer; Autogenomics INFNITI CYP2C19 assay can analyze genetic polymorphisms, which have a large impact on response to antidepressant treatment; while Affymetrix's CytoScan Dx can assess intellectual disability and congenital disorders by analyzing chromosomal mutations.

In the future, diagnostic tools for cancer may focus on next-generation sequencing (NGS).The technology in the field of molecular diagnostic tools will be further developed through the use of DNA and RNA sequencing for cancer diagnosis. Although the throughput and price of NGS have decreased dramatically by~100-fold over the past 10 years, we are still at least 6 orders of magnitude away from deep sequencing at the whole genome level.Currently, Ion Torrent has developed some NGS panels based on translation AmpliSeq, such as Oncomine Comprehensive Assay.They focused on using deep sequencing of cancer-associated genes to detect rare sequence variants.

Molecular diagnostic tools are available for cancer risk assessment.For example, Myriad Genetics' BRCA1/2 test assesses a woman's lifetime risk of developing breast cancer.In addition, some cancers do not always have obvious symptoms.It is useful to analyze people when they are not showing obvious symptoms, so cancer can be detected at an early stage.For example, the ColoGuard test can be used to screen people over the age of 55 for colorectal cancer.Cancer is a long-term disease with multiple steps of progression, and molecular diagnostic tools can be used in the prognosis of cancer progression.For example, Genomic Health's OncoType Dx test estimates breast cancer risk.Their technique could inform patients to seek chemotherapy if necessary by examining RNA expression levels in breast cancer biopsies.

With rising government support in DNA molecular diagnostics, it is expected that an increasing number of clinical DNA detection assays for cancers will become available soon.Currently, research in cancer diagnostics are developing fast with goals for lower cost, less time consumption and simpler methods for doctors and patients.