Next-Generation Sequencing and FFPE: Unlocking Genomic Insights

In recent years, advancements in genomic research accelerated at an astonishing pace, with next-generation sequencing (NGS) playing a central role in this revolution. For researchers and clinicians working with preserved tissue samples, the combination of NGS and formalin-fixed paraffin-embedded (FFPE) tissue has opened new doors in cancer research, disease diagnostics, and therapeutic development. Let’s explore the evolving intersection of next-generation DNA sequencing, FFPE samples, and how they are helping scientists unlock the secrets of human biology.

With the widespread availability of formalin-fixed paraffin-embedded (FFPE) tissue samples, researchers and pathologists now have a practical and powerful tool for investigating the tumor microenvironment and its immune-specific counterpart, the tumor immune microenvironment. In this blog, we explore how FFPE samples are being used to unlock the spatial, cellular, and molecular dynamics of the tumor microenvironment.

What is Next-Generation Sequencing?

Next-generation sequencing refers to a suite of technologies that allow for the high-throughput analysis of DNA and RNA. Unlike traditional Sanger sequencing, which sequences DNA one fragment at a time, next-generation DNA sequencing can process millions of fragments simultaneously. This allows researchers to gain a comprehensive view of genetic material more efficiently, accurately, and affordably than ever before.

The technology has made it possible to perform complex tasks like whole genome sequencing—analyzing an organism’s entire DNA sequence in one go—and transcriptomic analysis, which reveals how genes are expressed across different tissues and conditions.

In practical terms, NGS has become essential in fields like oncology, pathology, infectious disease, and pharmacogenomics. However, its power increases exponentially when paired with the vast repositories of FFPE tissue samples collected in clinical settings.

The Role of FFPE Tissue in Genomic Research

Formalin-fixed paraffin-embedded (FFPE) tissue is the standard method for long-term preservation of clinical biopsy and surgical specimens. FFPE samples are incredibly valuable for retrospective studies, allowing researchers to correlate genomic data with historical clinical outcomes.

However, extracting high-quality nucleic acids from FFPE tissue presents challenges due to the chemical cross-linking and degradation that occur during the fixation process. Fortunately, innovations in NGS library preparation, bioinformatics, and tissue processing have made it increasingly feasible to extract reliable DNA and RNA for next-generation sequencing. This has made FFPE-compatible NGS a game-changer in both research and clinical environments.

FFPE and Whole Genome Sequencing: A Retrospective Powerhouse

Whole genome sequencing provides an unbiased, comprehensive view of the entire genome, capturing both coding and non-coding regions. When paired with FFPE samples, it enables researchers to:

Identify mutations and structural variations that may have contributed to disease progression.
Study rare genetic disorders using archival tissue.
Examine tumor heterogeneity over time by analyzing serial biopsies.

The ability to perform whole-genome sequencing on FFPE samples is especially valuable in cancer genomics. It helps pathologists and oncologists detect actionable mutations, resistance mechanisms, and hereditary cancer risk—insights that directly influence patient care and treatment decisions.

Transcriptomic Analysis in FFPE Samples: Measuring Gene Expression

Transcriptomic analysis refers to the study of RNA transcripts that the genome produces under specific conditions. It provides essential insights into which genes are active or suppressed, and the extent to which they are expressed. In recent years, next-generation sequencing (NGS) has made transcriptomic analysis in FFPE samples more accessible and reliable.

Researchers now frequently use NGS-based transcriptomic analysis to characterize tumor subtypes through detailed gene expression profiling. This approach also helps identify both prognostic and predictive biomarkers, which are critical for understanding disease progression and guiding treatment strategies. Additionally, transcriptomic data derived from FFPE samples contribute significantly to unraveling the molecular mechanisms underlying various diseases.

While working with RNA from FFPE tissues can be technically challenging due to degradation during the fixation process, modern extraction protocols and advanced library preparation kits have significantly improved RNA sequencing outcomes. As a result, archived FFPE samples can now be used in retrospective studies to uncover gene expression patterns that correlate with patient responses or clinical outcomes.

Why FFPE-NGS Integration Matters

The integration of FFPE tissue with next-generation sequencing technologies bridges the gap between clinical practice and molecular research. This synergy provides several key advantages:

1. Retrospective Research Potential

FFPE tissue banks around the world house millions of preserved samples. When combined with NGS, these samples become a treasure trove for genomic discovery and validation.

2. Improved Diagnostic Accuracy

Next-generation DNA sequencing of FFPE samples allows clinicians to detect genetic mutations with a high degree of sensitivity and specificity, even from small or degraded samples.

3. Personalized Medicine

NGS enables the tailoring of therapies based on an individual’s genomic profile. FFPE-derived NGS data supports precision oncology and other fields where targeted therapies are rapidly evolving.

4. Cost and Time Efficiency

Leveraging existing FFPE samples for genomic studies eliminated the need for fresh tissue, reducing both costs and logistical barriers.

Overcoming Challenges in FFPE-NGS

Despite the remarkable benefits of combining FFPE samples with next-generation sequencing, several obstacles remain. One of the most common issues is the degradation of nucleic acids; the formalin fixation process tends to fragment and chemically modify the amount of usable material for sequencing. Furthermore, the complex nature of FFPE-derived sequences requires sophisticated bioinformatics tools to process and interpret the data effectively, due to the presence of crosslinked and fragmented nucleic acids.

To address these challenges, Superior BioDiagnostics applies optimized extraction methods and uses cutting-edge sequencing platforms specifically tailored for FFPE samples. With a team of skilled experts and a focus on quality at every stage, Superior BioDiagnostics is equipped to produce high-quality genomic data even from degraded or difficult specimens.

Applications of FFPE-Enabled Next Generation

The integration of FFPE samples with next-generation DNA sequencing is revolutionizing research across several fields. In cancer genomics, for example, scientists can now profile tumors by identifying somatic mutations, gene fusions, and copy number variations directly from archived tissue. In neurology, researchers study the molecular underpinnings of neurodegenerative diseases using historical brain specimens, gaining insights that were previously inaccessible.

Immunology also benefits from this approach, with scientists now able to explore gene expression patterns within the immune system using preserved tissues. Even in infectious disease research, FFPE samples allow for the identification of pathogen genomes in older tissue collections, offering new perspectives on disease outbreaks and transmission.

Across all of these disciplines, transcriptomic analysis and whole genome sequencing of FFPE tissue are delivering unprecedented insight into the biology, development, and potential treatment of a wide range of conditions.

The Future of FFPE and NGS

As next-generation sequencing technologies continue to evolve, so do the possibilities for extracting meaningful, actionable data from challenging sample types like FFPE. Advances in extraction chemistries, the increasing fidelity of sequencing instruments, and powerful bioinformatics platforms have transformed FFPE tissue from a problematic material into a valuable resource.

For institutions like hospitals, research universities, and biotech companies, this evolution means that massive archives of preserved tissue samples are no longer static collections—they’re dynamic reservoirs of untapped genomic information. Unlocking this potential could lead to breakthroughs in diagnostics, drug development, personalized therapies, and our broader understanding of human health.

Partner with Superior BioDiagnostics to Maximize Your FFPE Sample Potential

At Superior BioDiagnostics, we combine clinical precision with research-driven innovation to transform both malignant and normal FFPE tissue samples into actionable genomic insights. Whether you’re working with archived cancer specimens or healthy tissue controls, our proprietary products and optimized workflows are designed to ensure high-quality nucleic acid extraction and sequencing performance, even from the most degraded samples.

Our team brings deep expertise in next-generation sequencing, including transcriptomic analysis and whole-genome sequencing, and we’re equipped to handle a wide range of applications—from retrospective studies to clinical biomarker validation. With a full suite of customized services and specialized reagents developed in-house, Superior BioDiagnostics empowers you to maximize value from your FFPE samples. Are you ready to unlock the full potential of your FFPE samples with next-generation sequencing? Contact Superior BioDiagnostics today and discover how our team can support your next genomic research breakthrough.