Comprehensive Tumor Profiling Using NGS: Precision Oncology, Liquid Biopsy and Clinical Decision Support

How next-generation sequencing is transforming tumor profiling, liquid biopsy, and clinical decision-making in precision oncology

Molecular oncology is undergoing a fundamental transformation. Advances in next-generation sequencing (NGS), integrated bioinformatics, and clinically validated biomarker interpretation are enabling oncologists to move beyond single gene testing towards truly comprehensive, data-driven treatment selection.

During a recent Genomics Unlocked webinar, experts from OncoDNA, MGI, and Sistemas Genómicos discussed how integrated NGS workflows are transforming routine cancer diagnostics - shifting from sequential single-gene testing toward comprehensive multi-gene analysis in a single assay.

Historically, treatment selection relied on stepwise testing using methods such as immunohistochemistry (IHC), PCR, and qPCR, where each result guided the next biomarker to evaluate. Today, NGS enables simultaneous analysis of multiple clinically relevant genes, supporting faster therapeutic decisions while also enabling non-invasive monitoring through liquid biopsy and molecular surveillance.

This article highlights the key insights from that discussion. 

Moving Beyond Single-Gene Testing in Oncology

Modern oncology presents unique diagnostic challenges: tumor heterogeneity, limited and degraded FFPE material, increasing biomarker complexity, and the urgent need for fast, actionable results for rapid therapeutic decisions.

Traditional single-gene or small-panel assays struggle to meet these demands. NGS has become the preferred technology for precision oncology because it enables:

• Simultaneous detection of mutations, CNVs, and gene fusions

• Assessment of complex genomic signatures such as TMB, MSI, HRD and LOH

• Scalable testing from small laboratories to high-throughput reference centres

• Seamless integration with clinical interpretation and reporting platforms

As highlighted during the webinar, this shift represents a move toward standardized, data-driven oncology.

Engineered for Clinical Oncology: The Role of MGI Sequencing

High-complexity oncology panels require more than sequencing throughput. Clinical laboratories must also ensure data stability, uniform coverage, and reproducibility across challenging samples such as FFPE tissue and low-input DNA.

MGI’s sequencing platforms including the G99, G400, T1+, and T7, are designed to support these requirements across mid- and high-throughput laboratory environments.

At the core of these systems is DNA nanoball (DNB) sequencing technology, which minimizes several common sequencing artifacts, including:

• PCR duplicates

• Index hopping

• Error propagation

  
  

DNB sequencing uses circularized library fragments and rolling circle replication to generate highly uniform DNA nanoballs prior to sequencing, avoiding PCR amplification directly on the flow cell and reducing amplification bias.

For oncology applications, particularly those involving FFPE tissue or low-input DNA, this translates into:

• More uniform genome coverage

• More robust copy number variant (CNV) detection

• Greater sensitivity for low-frequency variants

  
  

These performance characteristics are critical for accurate tumor profiling, where uneven amplification or technical noise can directly influence therapeutic interpretation. Integrated workflows that automate steps such as library conversion, DNB generation, and flow cell loading further reduce operator variability, supporting consistent performance in routine clinical laboratory settings.

OncoDeep™: Broad Tumor Profiling in a Single Workflow

OncoDNA’s flagship assay, OncoDeep™, is designed to provide comprehensive tumor profiling within a single sequencing run.

The panel includes:

• 638 genes at the DNA level

• 22 genes at the RNA level for fusion detection

• Detection of SNVs, CNVs, gene fusions, LOH, MSI, HRD, and TMB

• Optimized coverage of clinically challenging regions such as the TERT promoter

Using hybrid capture chemistry and uniform sequencing, the assay supports reliable and consistent detection of SNVs, CNVs, fusions, and genomic signatures within a single assay. On the G400, laboratories can process up to 96 samples per flow cell, while lower-throughput systems such as the G99 allow scalable adoption for mid-volume testing environments.

Expanding into Liquid Biopsy: OncoSelect™

Beyond tissue-based profiling, the workflow includes OncoSelect, a liquid biopsy panel designed for circulating tumor DNA analysis.

Key features include:

• 74 clinically relevant genes

• Unique molecular identifiers (UMIs) for error correction

• Ultra-deep sequencing (~20,000× coverage)

• Detection of SNVs, fusions, HRR genes, and TERT promoter variants

This enables sensitive detection of low-frequency tumor variants for therapy selection, monitoring response to treatment, and potential minimal residual disease applications.

Real-World Validation: Experience from Sistemas Genómicos

Sistemas Genómicos, a leading Spanish reference laboratory with over 25 years of experience in genetic diagnostics, presented validation data supporting the integrated MGI/OncoDNA workflow.

A total of 90 samples (54 clinical and 36 reference) were analyzed. Libraries previously sequenced on alternative platforms were re-sequenced on the G400 to enable direct comparison.

Key findings included:

• Optimal performance at DNA inputs of 30–100 ng

• Reduced performance at very low input (6 ng), consistent with limitations observed across platforms

• 100% concordance for MSI and HRD

• Greater than 90% concordance for TMB

These results demonstrated equivalent analytical performance while supporting cost-efficient large-panel oncology testing.

Enabling Clinical Services Across Oncology Settings

Following validation of the OncoDeep assay on the G400, Sistemas Genómicos incorporated this workflow into its oncology testing portfolio.

Within this framework, the laboratory described service configurations that include:

• DNA-based tumor profiling (638 genes plus TMB, MSI, HRD)

• Combined DNA and RNA fusion analysis

• Integration of genomic profiling with selected protein biomarkers (including PD-L1 and CD8)

• Additional testing such as MGMT promoter methylation

These services support therapy selection across targeted treatment, immunotherapy, and chemotherapy, and reflect the laboratory’s validated implementation of the integrated workflow.

Bioinformatics Designed for Clinical Decision Support

Comprehensive tumor profiling requires robust analytical and interpretation frameworks capable of translating complex sequencing data into clinically meaningful insights.

OncoKDM, OncoDNA’s cloud-based platform, provides structured visualization and clinical interpretation of sequencing results. Detected genomic alterations are integrated with curated oncology knowledge to support evidence-based treatment decisions.

Key capabilities of OncoKDM include:

• Sample-level quality control metrics

• Variant and copy number visualization

• Fusion analysis display

• Calculation and reporting of genomic signatures (e.g., TMB, MSI, HRD)

• Evidence-linked therapy and clinical trial associations

• Downloadable data files (e.g., BAM, VCF, coverage reports)

To further support clinical decision-making, users can apply virtual panels to focus on specific gene sets or clinical contexts, allowing interpretation of the same sequencing dataset without requiring additional wet-lab experiments.

The platform also provides access to ongoing clinical trial information, enabling clinicians to identify relevant trial opportunities associated with detected genomic alterations. By centralizing interpretation and reporting within a validated framework, laboratories can streamline analysis workflows while maintaining analytical transparency and traceability.

Toward Longitudinal, Data-Driven Oncology

Looking ahead, speakers highlighted a clear evolution in cancer diagnostics. Oncology testing is evolving beyond static tumor profiling toward integrated, longitudinal molecular strategies that include:

• Expansion toward whole exome based tumor profiling

• Larger RNA and liquid biopsy panels exceeding 400 genes

• Tumor-informed minimal residual disease (MRD) monitoring

• Cohort-level analytics through oncology data intelligence platforms

• Greater automation across sequencing and library preparation

Together, these developments signal a shift from isolated genomic snapshots to continuous, data-driven oncology management.

As demonstrated during this webinar, integrating high-accuracy sequencing platforms from MGI with OncoDNA’s assay and interpretation framework validated in routine laboratory practice by Sistemas Genómicos, supports scalable, clinically actionable precision oncology.

Other resources

• Explore MGI sequencing platforms: https://mgi-tech.eu/sequencing-products

• Watch the full webinar on demand:  https://genomicsunlocked.com/ondemand/unlocking-precision-oncology-how-oncodna-and-mgi-provide-accessible-cpg-for-cancer-patients

• Visit Genomics Unlocked: https://genomicsunlocked.com/

FAQs

 1.        What does this integrated oncology workflow enable?
It enables laboratories to perform comprehensive tumor profiling, combining broad biomarker detection, high-accuracy sequencing, and structured clinical interpretation within a single workflow.

 2.        What types of cancer biomarkers can be analyzed?
The workflow supports detection of mutations (SNVs), copy number changes (CNVs), gene fusions, and genomic signatures such as TMB, MSI, HRD, and LOH.

 3.        Why is MGI sequencing used for oncology testing?
DNA nanoball (DNB) sequencing improves coverage uniformity and reduces technical artifacts, supporting accurate variant detection in challenging samples such as FFPE tissue and low-input DNA.

 4.        How are sequencing results translated into treatment recommendations?
Sequencing data is analyzed through OncoDNA’s OncoKDM platform, which links molecular findings to approved therapies, clinical trials, and curated scientific evidence.

 5.        Can this workflow be implemented in routine clinical laboratories?
Yes. The integrated workflow has been validated using real clinical samples and is designed for scalable implementation across mid- and high-throughput oncology laboratories.