Mass Spectrometry: Unlocking Deeper Insights for Geneticists

Published: November 28, 2024

by David Graham, PhD, Head of Scientific Business Development

Mass spectrometry – A Game Changer for Geneticists Unlocking Deeper Biological Insights

At the recent ASHG Annual Meeting in Denver, one question stood out among many intriguing discussions:
“I’m a geneticist—why would I be interested in mass spectrometry?”

For some attendees, the connection between genetics and mass spectrometry (MS) was obvious.  For others, it was a revelation. Many people forget that the human genome project relied on mass spectrometry for sequencing, so in many ways MS ushered in the genomics era. MS also was used to gain the first insights into Histone acetylation and to this day is used to study DNA methylation as it’s able to differentiate between 5-methylcytosine (5mC) and 5hmC a chemical alteration that lies at the heart of epigenetics, so in many respects MS ushered in the era of epigenetics.  

Today, modern MS-based approaches —such as analyzing proteins, small-molecule metabolites, or lipid changes—offer unparalleled insights into how genetic disruptions or modifications translate into biochemical outcomes. These insights go far beyond the information traditional genetic tools can provide.

Take drug discovery as a comparison. Understanding a drug’s pharmacokinetics (PK) is essential but so is understanding its metabolism and off-target effects, which requires pharmacodynamic studies. The same principle applies to gene editing, knock-ins, or knock-outs. While genomic tools reveal the “what,” mass spectrometry reveals the “how” and “why,” providing deeper answers about the biochemical ripple effects of genetic changes.

Mass Spectrometry: Bridging the Gap from Genes to Function

At its core, genetics tells us about blueprints—how DNA is transcribed, translated, and modified to regulate proteins, metabolites, and lipids. But this blueprint isn’t static as complex regulatory mechanisms including miRNAs and epigenetic changes, like those described above can vary gene expression vastly. The resulting biochemical activities within cells and tissues often vary significantly, even among individuals with identical genetic backgrounds or in the same individual in different populations of cells.

This is where MS excels. While traditional genetic approaches that provide a high-level view of a system, MS allows for the direct downstream measurement and quantification of molecules, painting a real-time picture of cellular activity. This data provides a bridge between genetic information and functional biology, helping researchers understand how a gene’s influence manifests in the intricate web of biological processes.

For geneticists exploring the outcomes of gene editing or studying the effects of single nucleotide polymorphisms (SNPs), mass spectrometry provides actionable insights that can uncover how proteins, metabolites, and lipids respond to changes at the genetic level. These insights are critical for connecting genetic variations to phenotypic changes and understanding the broader biological implications of genetic research.

A Powerful Tool for Studying Gene-Environment Interactions

MS approaches, like targeted proteomics can be used for the direct quantitative analysis of protein expression or even post-translational modifications of proteins that may be targeted by knock-out or knock in experiments.  Unlike antibody based proteomics approaches, off target protein changes can be measured using chemical tagging approaches that allow for the direct comparison of protein expression levels under multiple conditions in a single multiplexed experiment. MS based metabolomics experiments can be used to quantitate levels of metabolite expression and MS based lipidomics approaches can do the same for lipids, sterols and even signaling (oxi) lipids.   targets Genetics often focuses on internal blueprints, but biology does not operate in isolation.

By measuring changes in protein, metabolite and lipids levels, mass spectrometry can capture the real-time outcomes of gene-environment interactions. These insights allow investigators to go far beyond gene association studies, bringing mechanistic insights into how genetic changes contribute to health and disease.

Multiomics: Expanding the Boundaries of Genetic Research

For geneticists ready to look beyond sequencing, integrating proteomics, metabolomics and lipidomics into genomic studies can transform the depth and scope of your research. Multiomics approaches provide a holistic view of biology, combining the precision of genetic insights with the dynamic understanding of functional biology.

Allumiqs specializes in proteomics, metabolomics and lipidomics, providing a collaborative approach in helping researchers bridge to these complementary disciplines. We also have a highly skilled team dedicated to data integration and interpretation with scientists on staff skilled in multiple disciplines. Whether you’re looking to explore the downstream effects of a genetic variant or seeking to understand how genes and environment shape a phenotype, we’re here to support your success. Our tailored solutions help you uncover the complete story hidden in your data, offering clarity and confidence as you move from hypothesis to discovery.