The Role of Clinical NGS in Patient Care

Introduction

Next-Generation Sequencing (NGS) is transforming disease diagnosis and treatment by enabling fast and precise genetic analysis. This advancement has paved the way for personalized medicine, allowing for tailored treatment strategies based on an individual’s unique genetic profile.

From diagnosing rare diseases to guiding targeted cancer therapies, NGS is rapidly becoming an essential component of modern healthcare, transforming the way medical conditions are detected and treated. This article explores how NGS is applied in clinical settings, its benefits, and its growing impact on patient care.

What is Next-Generation Sequencing (NGS)?

NGS is a technology used to decipher DNA or RNA sequences with high throughput and precision, enabling the study of genetic variations linked to diseases and other biological processes. First introduced for commercial use in 2005, NGS was originally known as “massively parallel sequencing” due to its ability to simultaneously sequence multiple DNA strands. This marked a significant advancement over traditional sanger sequencing, which relies on capillary electrophoresis (CE) to analyze DNA one strand at a time.

By sequencing millions of fragments in parallel, NGS uncovers genetic variations, and patterns that would be challenging or impossible to detect using older methodologies like Sanger sequencing. This ability to process vast amounts of genetic information  in a single run has made NGS an irreplaceable tool in areas such as oncology, rare disease diagnostics, and infectious disease management.

In the NGS workflow, maintaining sample quality is important for obtaining accurate and reliable results. Tools like omnomicsQ address this need by offering real-time monitoring of samples and delivering a comprehensive quality management system for clinical NGS workflows, allowing laboratories to automate data quality control for each sample efficiently. This proactive quality control minimizes errors and avoids costly reruns, safeguarding the integrity of the data and improving the overall efficiency of the sequencing process.

How Clinical NGS is Used in Patient Care

1. Diagnose Diseases

NGS plays a critical role in diagnosing diseases by finding genetic or molecular causes that might remain undetected through traditional diagnostic methods. Its ability to sequence entire genomes or targeted gene panels allows detection of genetic abnormalities associated with inherited disorders, cancers, and rare diseases, helping clinicians to identify the genetic basis of conditions with high accuracy.

NGS has revolutionized the field of medical genetics by providing a powerful, high-throughput, and cost-effective approach to diagnosing rare genetic diseases and inherited cancers. Rare genetic diseases are often caused by single-gene mutations that can be challenging to identify using traditional diagnostic methods. NGS offers several advantages in this domain: 

• Comprehensive Genetic Analysis: NGS allows for whole-genome sequencing (WGS), whole-exome sequencing (WES), and targeted gene panels, enabling the identification of mutations across the entire genome or specific regions of interest.
• Detection of Complex Variants: It can identify single nucleotide variants (SNVs), insertions/deletions (INDELs), copy number variations (CNVs), and structural rearrangements that might be missed by conventional methods such as Sanger sequencing.
• Early and Accurate Diagnosis: Many rare diseases manifest without any symptoms, making early diagnosis challenging. NGS can pinpoint the underlying genetic cause, facilitating early intervention and management.
• Uncovering Novel Mutations: As our understanding of genetic diseases evolves, NGS helps in discovering previously unknown variants associated with rare conditions, leading to better classification and prognosis.

Inherited cancers arise from germline mutations in cancer-associated genes. NGS has transformed the approach to hereditary cancer diagnosis by enabling:

• Identification of High-Risk Mutations: NGS helps detect pathogenic variants in well-known cancer susceptibility genes such as BRCA1/2 (breast and ovarian cancer), TP53 (Li-Fraumeni syndrome), and APC (familial adenomatous polyposis).
• Multigene Panel Testing: Rather than testing one gene at a time, NGS allows simultaneous analysis of multiple cancer-associated genes, increasing diagnostic yield and efficiency.
• Early Cancer Risk Assessment: Individuals with a family history of cancer can undergo genetic screening to assess their inherited risk and take preventive measures such as increased surveillance or prophylactic surgery.
• Improved Treatment Strategies: Understanding an individual’s genetic makeup can guide personalized treatment approaches, such as targeted therapies (e.g., PARP inhibitors for BRCA-mutated cancers).

To uphold accuracy and reliability, laboratories frequently participate in External Quality Assessment (EQA) programs, such as those provided by the European Molecular Genetics Quality Network (EMQN) and Genomics Quality Assessment (GenQA). These programs ensure consistency and dependability of diagnostic results across different institutions. EQA schemes involve rigorous benchmarking of the entire laboratory workflow, from sample preparation to data interpretation. For patients, this means that NGS-based diagnoses follow standardized protocols, reducing the likelihood of errors and enhancing confidence in the results.

2. Personalize Treatments

NGS plays an important role in personalizing treatments by aligning therapies with the unique genetic profiles of patients. By analyzing the specific genetic variations that might influence health or disease, NGS enables clinicians to tailor therapeutic approaches, improving their effectiveness and reducing the likelihood of adverse effects. 

NGS plays a crucial role in personalized medicine by aligning treatments with each patient’s unique genetic profile (1). By identifying specific genetic variations that may impact health or disease, NGS empowers clinicians to customize therapeutic strategies, enhancing treatment efficacy while minimizing the risk of adverse effects. In oncology, NGS enables the identification of genetic mutations specific to tumor cells (2), facilitating the selection of targeted therapies that are most likely to be effective for individual patients. By providing detailed insights into the molecular profile of a tumor, NGS helps oncologists move beyond traditional one-size-fits-all treatment approaches and instead implement precision interventions tailored to the patient’s unique genetic alterations.

To ensure the reliability and applicability of this process, tools like  omnomicsNGS facilitate the interpretation of sequencing data. These solutions comply with guidelines set by the American College of Medical Genetics and Genomics (ACMG) and the College of American Pathologists (CAP), guaranteeing accurate and clinically relevant results. Adhering to standardized protocols and guidelines reduces variability and ensures the consistent delivery of high-quality patient care.

3. Predict Genetic Risks

NGS is essential for predicting genetic risks by examining an individual’s DNA to identify predispositions to specific genetic conditions (3). By identifying variations in genes linked to diseases, NGS allows healthcare providers to assess the likelihood of a person developing conditions such as hereditary cancers, cardiovascular disorders, or neurodegenerative diseases. This knowledge empowers health care professionals to take proactive steps, such as adopting early interventions, targeted screenings, or preventive care strategies, that could significantly reduce the risk or impact of these conditions. For families with a history of genetic diseases, this capability offers an important tool to manage and mitigate health risks across generations.

In clinical settings, handling sensitive data during genetic risk assessments requires strict adherence to regulatory frameworks. While frameworks like the General Data Protection Regulation (GDPR) in Europe and the Health Insurance Portability and Accountability Act (HIPAA) in the U.S. prioritize safeguarding sensitive patient information, the In Vitro Diagnostic Regulation (IVDR), issued by the European Union, focuses on ensuring that diagnostic products are safe and effective for patient use. These regulations mandate robust data protection measures, enforce transparency in how genetic data is used, and support patient rights to privacy. This secure environment fosters trust and confidence in the use of NGS for patient management, while also paving the way for its broader adoption.

4. Monitor Therapy Responses

NGS is instrumental in monitoring therapy responses, offering a comprehensive molecular-level view of how treatments impact a patient’s condition. This helps clinicians make evidence-based adjustments to therapies in real-time, improving patient outcomes and reducing unnecessary delays in care. NGS can evaluate treatment efficacy by tracking genetic markers that reflect disease progression or regression. For example, in cancer care, circulating tumor DNA (ctDNA) can be analyzed to detect residual disease or emerging resistance mutations during treatment (4). If a therapy is not producing the desired effect, NGS results can guide the decision to modify the treatment plan instantly, ensuring the approach remains aligned with the patient’s evolving needs. This ability to adapt treatments dynamically is key to achieving better clinical results.

The reliability of NGS-based therapy monitoring is further strengthened by integrating tools like omnomicsQ, which ensures real-time quality control of genomic samples. By flagging suboptimal samples early, omnomicsQ safeguards the accuracy of sequencing data, reducing errors and preventing costly reruns. This proactive approach ensures that clinicians receive reliable information to guide therapy adjustments, ultimately supporting better clinical outcomes.

Benefits of Clinical NGS in Healthcare

1. Improve Diagnostic Precision

NGS significantly improves diagnostic precision by identifying genetic variations with remarkable accuracy. This is achieved through advanced tools and methodologies that ensure reliable results.  NGS platforms validate their performance against well-established reference standards, such as those provided by the National Institute of Standards and Technology (NIST) and Horizon. These benchmarks serve as critical quality controls, ensuring that the sequencing process remains consistent and precise across diverse applications.

NGS excels at detecting genetic mutations, structural variations, and other abnormalities that might elude traditional diagnostic methods. By capturing the full spectrum of genomic information, it minimizes the risk of missed or inaccurate findings. This comprehensive approach allows healthcare providers to identify underlying genetic causes of diseases with greater certainty, directly influencing clinical decision-making. The ability of NGS to deliver high-resolution insights into genetic data is especially impactful in complex cases. It supports the diagnosis of rare conditions, uncovers actionable mutations, and aids in refining treatment strategies based on specific genetic profiles.

2. Accelerate Decision-Making

NGS accelerates clinical decision-making by delivering rapid and accurate insights that inform patient care. The turnaround time for NGS test results can vary depending on several factors, including the type of test, the complexity of the analysis, and the laboratory’s workflow. Automated systems, such as omnomicsQ, play a critical role in optimizing this process. Tools like omnomicsQ can identify low-quality samples early in the sequencing workflow, preventing unnecessary delays. By ensuring that only high-quality, actionable data proceeds to analysis, they significantly reduce turnaround times.This efficiency enables clinicians to make timely decisions, which can be critical in cases where rapid intervention could alter a patient’s prognosis.

In infectious disease management, NGS offers a transformative advantage by providing comprehensive data on pathogens in a single sequencing run. Unlike conventional microbiological methods, which might take days for organism growth and are limited in scope, NGS can simultaneously identify multiple species, detect antimicrobial resistance genes, and sequence entire bacterial genomes. This capability is important for outbreak response, as it allows healthcare teams to quickly identify pathogens, trace their sources, and implement targeted control measures.

3. Reduce Healthcare Costs

Efficient use of resources in healthcare is important for reducing costs, and NGS plays a significant role in achieving this. By automating validation and quality control processes, NGS minimizes manual errors that can lead to inaccurate results or repeat testing.  This automation ensures that laboratory workflows run smoothly, reducing unnecessary tests and optimizing the use of lab resources. For example, streamlined processes allow for the simultaneous analysis of multiple samples, saving both time and money compared to traditional sequencing methods.

The ability of NGS to consolidate multiple diagnostic tests into a single protocol also contributes to cost-effectiveness. Instead of performing separate tests for each genetic or molecular marker, NGS offers a comprehensive approach.  This reduces the need for redundant procedures, lowers reagent costs, and shortens turnaround times. These efficiencies make NGS an attractive option for healthcare systems aiming to deliver high-quality care while managing expenses effectively.

4. Facilitate Preventive Measures

By identifying genetic risks early, NGS enables proactive healthcare strategies that can significantly improve patient outcomes. Through comprehensive genomic analysis, NGS uncovers predispositions to various genetic conditions, allowing healthcare providers to intervene before symptoms manifest. For instance, identifying mutations associated with hereditary cancers, such as BRCA1 or BRCA2, provides opportunities for early surveillance or preventive measures, like prophylactic surgeries or targeted lifestyle modifications. This foresight reduces the likelihood of complex treatments down the line, which often come with higher costs and potential complications. Preventive measures informed by NGS can also include personalized screening schedules for conditions like cardiovascular disease or diabetes, tailored to an individual’s genetic risk profile. These strategies not only lower the overall burden of disease but also improve the quality of life for patients by minimizing avoidable health crises.

Impact of Clinical NGS on Patient Outcomes

1. Detect Conditions Early

By identifying genetic or molecular markers linked to various diseases, NGS allows for early diagnosis that was previously unattainable with traditional diagnostic methods. This capability is particularly impactful for conditions like cancer, where pinpointing mutations in their initial stages can lead to significantly better outcomes. One of the key advantages of NGS is its ability to analyze multiple genes simultaneously, using the same protocol regardless of the suspected condition. This broad-spectrum approach is invaluable for identifying rare or subtle genetic mutations that could otherwise be missed. The earlier a disease is detected, the more treatment options become available, many of which are less invasive and more effective in the early stages. 

For hereditary conditions, NGS allows healthcare providers to assess risks even before symptoms manifest, giving patients the chance to adopt preventive measures. Similarly, in infectious diseases, rapid sequencing of microbial DNA or RNA can spot pathogens before symptoms escalate, enabling timely and precise treatment to prevent complications.

2. Enhance Treatment Effectiveness

NGS increases treatment effectiveness by enabling precision therapies that align with a patient’s unique genetic profile. By analyzing the genetic variations underlying a disease, NGS provides clinicians with the data needed to select therapies that target specific molecular pathways. This ensures that treatments are more likely to succeed while minimizing the risk of unnecessary side effects. For example, in oncology, identifying actionable mutations in a tumor’s DNA allows clinicians to prescribe targeted therapies, such as tyrosine kinase inhibitors or immune checkpoint inhibitors, which are designed to interfere with the exact mechanisms driving cancer growth.

3. Optimize Long-Term Management

Chronic diseases often require adaptable care strategies, as their progression can vary over time. NGS supports this by providing clinicians with detailed genetic and molecular insights, which can be revisited and analyzed as a condition evolves.For reliable long-term management, robust validation of genomic assays is critical. Tools like omnomicsV ensure that genomic tests meet stringent sensitivity and specificity requirements through comprehensive validation workflows. This ensures that clinicians have dependable data to revisit and analyze over time, allowing them to make informed adjustments to treatment plans and care strategies with confidence.

In addition to tracking disease progression, NGS-based monitoring can also detect emerging resistance to treatments, particularly in conditions like cancer or chronic infections. By sequencing and analyzing a patient’s genomic data at multiple intervals, it becomes possible to identify genetic mutations that might render current therapies less effective. Early detection of such resistance supports timely changes in treatment strategies, improving the likelihood of maintaining disease control.

4. Improved Patient Outcomes

High-quality NGS workflows, developed under stringent regulatory standards like ISO 13485, are essential for enhancing patient outcomes across diverse populations. These workflows ensure the accuracy and reliability of diagnostic processes, directly influencing the effectiveness of therapeutic decision-making. By delivering precise genetic insights, NGS empowers clinicians to confidently identify underlying conditions, minimizing the risk of misdiagnosis and preventing delays or complications in treatment.

The advantages of NGS extend to treatment planning as well. By leveraging detailed genetic data analyzed through tools like omnomicsNGS, healthcare providers can generate comprehensive variant interpretation reports that comply with best practice guidelines such as American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) (5, 6). This enables planning of targeted interventions tailored to each patient’s unique genetic profile, reducing the risk of ineffective treatments and minimizing adverse effects.

Furthermore, integrating automation into NGS workflows—leveraging tools like omnomicsQ for real-time genomic sample quality monitoring—ensures that only high-quality samples advance to analysis. This automated quality control reduces human error, enhancing both efficiency and consistency in sequencing processes. Reliable and reproducible results are particularly crucial in time-sensitive scenarios, where rapid and accurate genetic insights can drive critical treatment decisions, ultimately leading to improved patient outcomes.

Examples of Clinical NGS Applications

1. Cancer Genomics

• Tumor Profiling: NGS identifies somatic mutations, copy number variations (CNVs), and gene fusions in tumors, aiding in personalized cancer treatment.
• Minimal Residual Disease (MRD) Detection: Helps monitor cancer recurrence by detecting low levels of circulating tumor DNA (ctDNA).
• Pharmacogenomics in Oncology: Guides targeted therapy decisions based on genomic alterations (e.g., guiding targeted therapies like tyrosine kinase inhibitors for EGFR mutations in lung cancer,  PARP inhibitors for BRCA mutations in ovarian cancer)

2. Inherited Disease Diagnosis

• WES & WGS: Used for diagnosing rare genetic disorders, especially in pediatric patients with undiagnosed conditions.
• Carrier Screening: Helps prospective parents understand their risk of passing on inherited diseases (e.g., cystic fibrosis, Tay-Sachs disease).
• Newborn Screening: NGS enables early detection of metabolic and genetic disorders for timely intervention.

3. Infectious Disease Genomics

• Pathogen Identification: NGS detects bacterial, viral, and fungal pathogens with high accuracy (e.g., SARS-CoV-2 sequencing for COVID-19 surveillance).
• Antimicrobial Resistance (AMR) Profiling: Identifies genetic markers associated with antibiotic resistance, guiding effective treatment.
• Viral Evolution & Epidemiology: Tracks viral mutations to inform vaccine development and outbreak containment strategies.

Conclusion

Clinical NGS is both a transformative technology and a practical tool driving advancements in patient care. Its ability to provide precise diagnostics, personalize treatments, and enable preventative strategies is reshaping healthcare delivery. As its applications continue to expand, NGS is a key element for more effective, informed, and patient-centered care. Euformatics provides laboratories with comprehensive solutions for quality control, validation, and variant interpretation, ensuring compliance with industry standards. Our unique, transparent price configurator empowers labs to plan their budgets with clarity, supporting decision-making with ease. Visit our website to learn more or book a demo to explore how our solutions can enhance your lab’s NGS workflows.

FAQ

What Is Clinical NGS?

Clinical NGS (Next-Generation Sequencing) is a rapidly growing technology that analyses DNA or RNA to detect genetic variants, aiding in disease diagnosis, treatment planning, and the advancement of personalized medicine.

What Is NGS Testing For?

NGS testing detects genetic variation including point mutations, copy number alterations, and gene fusions, to aid in disease diagnosis, treatment decisions, and advance personalized medicine.

What Does NGS Stand For?

NGS stands for Next-Generation Sequencing, a technology for rapid and accurate genetic analysis.

What Are the Benefits and Limitations of Using Clinical NGS in Patient Care?

Benefits: Early diagnosis, personalized treatments, and targeted therapies.

Limitations: High costs, complex data interpretation, and ethical concerns.

References

1. Morganti, Stefania, Paolo Tarantino, Emanuela Ferraro, Paolo D’Amico, Giulia Viale, Dario Trapani, Bruno Achutti Duso, and Giuseppe Curigliano. “Complexity of genome sequencing and reporting: next generation sequencing (NGS) technologies and implementation of precision medicine in real life.” Critical reviews in oncology/hematology 133 (2019): 171-182.
2. Mansfield S,  Park, Mullane D. “ Identification, Prioritization, and Treatment of Mutations Identified by Next-Generation Sequencing”. American Society of Clinical Oncology Educational Book Volume 38, May 2018.
3. Kamps, Rick, Rita D. Brandão, Bianca J. van den Bosch, Aimee DC Paulussen, Sofia Xanthoulea, Marinus J. Blok, and Andrea Romano. “Next-generation sequencing in oncology: genetic diagnosis, risk prediction and cancer classification.” International journal of molecular sciences 18, no. 2 (2017): 308.
4. Schwaederle, Maria, Ranajoy Chattopadhyay, Shumei Kato, Paul T. Fanta, Kimberly C. Banks, In Sil Choi, David E. Piccioni et al. “Genomic alterations in circulating tumor DNA from diverse cancer patients identified by next-generation sequencing.” Cancer research 77, no. 19 (2017): 5419-5427.
5. Richards S, Aziz N, Bale S, et al. “Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.” Genetics in Medicine. 2015 May;17(5):405-24.
6. Li M , Datto M, Duncavage E, et al. “Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists”.  The journal of molecular diagnostics. 2017 Jan;19(1):4-23.

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