This post continues our series on molecular biology, which began with a discussion on informatics in biopharma R&D. In this installment, we’ll provide an overview of some exciting trends in precision medicine – especially as it relates to targeted cancer therapeutics.
Personalized vs. Precision Medicine — What’s the Difference?
Although many people use “precision medicine” and “personalized medicine” interchangeably, they technically mean different things. In a report published by the National Research Council in 2011, concerns were raised that the word “personalized” could create a false expectation that unique treatments are being created for each individual. While it is true that many new approaches to healthcare consider an individual’s unique allelic expression, resultant proteins, and other substances in the body, many authorities prefer the term “precision medicine” for this emerging field.
Rather than creating a completely custom plan for each person, precision medicine classifies individuals into subpopulations based on their susceptibility to a particular disease, or their response to a specific treatment. This classification enables any given treatment to be concentrated on those who are most likely to benefit, sparing expense and side effects for those who will not.
Genetic sequencing – a laboratory technique used to either determine the entire genetic makeup of an organism (known as whole genome sequencing) or to pinpoint the details of a single targeted gene – has been the single greatest factor driving the emergence of precision medicine.
The Traditional Sanger sequencing method was a low throughput technique requiring four separate sequencing reaction steps, and although it remains the foundation for genome sequencing, it presents significant barriers for use in medicine. The Sanger process is slow, can only handle short single fragments at a time and due to its multiple reaction sequences tends to be cost prohibitive for many organizations.
Next-generation sequencing (NGS) and high-throughput sequencing (HTS) are new technological advances which use the same essential methodology as Sanger sequencing but also allow much larger sample volumes — up to hundreds of millions of DNA molecules in parallel — to be sequenced quickly. These technologies enable researchers to detect abnormalities such as those caused by cancer – even when potentially harmful variations in genes occur at a low frequency.
As you might expect, these technologies offer significant advantages over the “one size fits all” approach of traditional medicine. Although precision techniques are still relatively new, using the patient’s genetic profile to guide treatment is already showing significant promise as a way to deliver higher levels of accuracy and effectiveness in health care.
But genetic sequencing in and of itself isn’t the end goal. It’s instead an enabling technology that makes precision medicine possible and provides limitless therapeutic possibilities.
The Promise of “Omics”
In the first article of this series, we mentioned an emerging group of biopharma disciplines which have become collectively known as the “-omics,” since each one ends with the suffix -omics.
Each of these omics fields focuses on the identification, measurement, and investigation of a specific type of molecule within a living system . Individually, these narrow results provide only limited therapeutic insight,. But when combined, they take our genetic understanding to a significantly higher level. This multi-disciplinary approach, sometimes called “multi-omics,” analyzes a patient’s genetic profile in combination with a variety of other factors and provides a more complete picture of the links between health and disease.
Omics-based strategies include:
- Genomics — The study of the genome – the DNA sets that make up organisms – including how they evolve and can be edited.
- Epigenomics — The study of epigenetic changes in cells, which are the chemical changes that cause genes to be “switched” on or off without changing the DNA sequence.
- Proteomics — Analysis of proteins and peptides, typically performed using various mass spectrometry (MS) instruments.
- Transcriptomics — The study of RNA molecules. A transcriptome is the complete set of RNA transcripts, a kind of “map” of gene expression patterns in cells or tissues. This can provide insights into their functional states, and may eventually help determine why certain diseases, notably cancer, occur.
- Metabolomics — Profiling of biological fluids to determine the current state of a cell or organism. This can be done almost instantly using MS and nuclear magnetic resonance (NMR) technologies, and more recently with analytical techniques like ion mobility spectrometry (IMS).
- Phenomics — A branch of science that explores how genes respond to environmental changes, such as drugs or toxic substances, including how we adapt and why we’re affected by diseases.
Modern NGS and HTS techniques are critical to each of these disciplines, and thus to the ongoing evolution of precision medicine. Speed and accuracy are essential when lives are at stake, and the technologies and platforms supporting the labs which use these methods must be equally robust and flexible.
Leveraging LIMS in Next-Generation Sequencing
NGS is a multi-step process that requires a complex mixture of reagents for each sample. It begins with the extraction of one or more samples, using various techniques to ensure that they provide researchers with a sufficient quantity of high-quality DNA or RNA. Researchers can work from a single sample or process dozens of samples at once.
The “library” that results from these samples can literally contain millions of fragments, which must be prepared ahead of time to produce a large enough pool of sequences, adding adapters that will enable the samples to be analyzed. In addition, RNA samples must be converted to cDNA prior to sequencing.
After the samples are extracted, purified (and in the case of RNA converted to cDNA) and associated with the correct sequencing adapters, the “library” is ready to be sequenced.
It undergoes quantification via PCR as a necessary step to sequencing which ensures the quality and efficiency of the resultant sequencing routine. The final result of the sequencing process is that the library is amplified into millions or even billions of clusters which are individually “read” and recorded. The results are then analyzed and validated using specialized software capable of interpreting the vast amounts of data generated.
Because sequencing is now being used to diagnose patients or for criteria matching to ensure inclusion into clinical studies the importance of accurate results can’t be overstated and goes far beyond what would be sufficient for academic study.
LIMS technology streamlines these processes considerably, helping to ensure more accurate outcomes by providing standardized tests, managing reagent preparations, loading controls, and using quality management processes to ensure the validity of the results.
A LIMS is invaluable in genetic sequencing workflows – not only as a centralized hub for data, but as a management tool capable of automating certain workflows. For example, a researcher might create a plate layout and send it to an instrument to perform the different stages of NGS. The instrument’s analysis can then be fed back into the LIMS automatically with minimal intervention by the technician, providing greater accuracy and precision. And the best LIMS also contain advanced analytics tools that leverage AI and machine learning to allow a researcher or clinician to determine probabilities of success and failures for treatment.
LIMS can also help to ensure that proper controls and validation standards are being used for the test. In addition, LIMS provides advantages outside the lab by defining, organizing and disseminating patient information linked to tested samples – all while ensuring patient confidentiality using transmission protocols that comply with Health Level 7 (HL7) standards.
The LabVantage Advantage
In a world where traditional medicine is giving way to precision diagnostics, a workflow-based application like LabVantage LIMS can help technicians and clinicians alike by ensuring speed, consistency, accuracy, and precision in the information they use to diagnose and treat.
LabVantage offers multiple ready-to-go workflows out of the box, designed specifically for a wide variety of NGS and omics-related diagnostic processes. These run the gamut from COVID-19 workflows to processes compatible with leading NGS companies – including Illumina, Qiagen, Agilent and others. This robust collection includes workflows for nucleic acid extraction, quantitation, normalization, library preparation and fragment analysis for technologies such as whole genome sequencing, solid tumor sequencing, Myeloid 54 targeted mutation, PyroMark Q96, Gene rearrangement workflows, BCR-ABL, Luminex workflows, MiSeq, NextSeq, and more.
In addition, LabVantage provides a built-in patient scheduler, and comes with an out-of-the-box HL7 interface component. This streamlines patient interactions and makes it easy to implement the software into clinical diagnostic settings.
Learn more about LabVantage’s pre-packaged LIMS for molecular and clinical diagnostics, or contact us today to discuss your precision medicine needs.