Genes, as the fundamental units of heredity, encode the instructions essential for the development, functioning and reproduction of living organisms. They represent pivotal elements for unravelling the molecular underpinnings of biological processes and disease mechanisms. Genomics, the comprehensive study of genetic material, aims to elucidate the roles and regulatory dynamics of genes in shaping biological functions at the molecular level.
Genomics encompasses various specialised areas of study, including functional genomics. Let’s look more closely at the specifics of functional genomics.
Understanding the complexities of functional genomics
Functional genomics extends beyond the study of individual genes to investigate the complex relationships between genes and the phenotypic traits they influence. It is distinct from structural genomics, which focuses on the physical properties of genomes, including sequencing and mapping. By advancing our understanding of the functional role of genetic information, functional genomics provides a critical foundation for translating genomic discoveries into practical applications in human health and biology.
This significant potential for clinical translation could contribute to advancements in drug discovery and precision medicine. By facilitating the identification and characterisation of genes and biological pathways associated with disease, functional genomics provides a cornerstone for the development of targeted therapeutic strategies to address specific pathological conditions.
Why is functional genomics important?
Functional genomics is a crucial part of research and development within healthcare because it closes the gap between genetic information and biological function, facilitating a deeper understanding of gene roles and their implications in health and disease.
- Functional genomics assigns functions to genes and non-coding regions, revealing their roles in biological processes.
- It enables the identification of molecular pathways and networks underlying disease mechanisms, facilitating the discovery of novel biomarkers and therapeutic targets.
- By correlating genetic variations with individual health outcomes, functional genomics drives progress in precision medicine and the development of highly targeted therapeutic interventions.
- This field also harnesses big data and artificial intelligence, utilising advanced computational tools to model complex interactions and interpret large-scale datasets, optimising approaches to improve patient outcomes.
Technologies and tools for functional genomic analysis
A wide range of experimental, computational and analytical methodologies are employed to investigate the roles, interactions and regulatory mechanism of genes and their associated products. Below, we explore some of the most commonly utilised approaches in this field.
Epigenomic tools
Epigenomic tools in functional genomic analysis refer to the methods and technologies used to study heritable changes in gene expression that don’t involve alterations to the underlying DNA sequence, known as epigenetics. These tools investigate mechanisms which regulate gene activity and play crucial roles in development, cellular differentiation and disease.
There are many different epigenomic tools. Some of the most common include:
- Chromatin immunoprecipitation followed by sequencing, which is used to analyse protein-DNA interactions, such as histone binding.
- DNA methylation analysis to identify patterns that play an essential role in gene regulations.
- Histone modification profiling, continue with methods such as mass spectrometry are used to map out different histone modifications present in the genome, which provides information about chromatin structure and gene regulation.
- Whole-genome bisulphite sequencing, which is a technique that enables genome-wide analysis of DNA methylation patterns at single-nucleotide resolution.
Transcriptomics
Transcriptomics is a branch of molecular biology that focuses on the study of an organism’s transcriptome – the complete set of all RNA transcripts produced in a cell or tissue at a specific time. The transcriptome provides valuable information about the gene expression profile and regulatory mechanisms that are active in a particular biological context. This is importance because this information provides better understanding of disease biomarkers, disease development and progression, and which therapies may prove most effective. Transcriptomics tools include RNA sequencing, microarray analysis and the use of transcriptome analysis software like DESeq, edgeR and Cufflinks.
Proteomics
Proteomics refers to the large-scale analysis of proteins to understand their role in various cellular processes – from providing structural support for cells, tissues and organisms, to catalysing biochemical reactions, recognising and neutralising harmful pathogens to storing essential nutrients and enabling cells to interact with one another. Proteomics complements functional genomics by giving researchers a deeper understanding of how genes are translated into functional proteins and how these proteins contribute to biological processes. By integrating the two, it may be possible to better decipher the molecular mechanisms underlying disease.
Functional genomics technology platforms
Advances in technology have revolutionised functional genomics by making it possible to analyse entire genomes, transcriptomes and proteomes with unparalleled speed and accuracy. What would previously have required extensive manual processing (which could carry a significant risk of human error) can now be performed by high throughput sequencing technologies like RNA-seq, which allow researchers to quantify gene expression globally, while tools like CRISPR-Cas9 enable precise gene editing and silencing to study gene function.
These innovations have drastically reduced costs, increased data resolution and opened up new routes to understanding gene regulation, interaction and their roles in health and in disease.
Single cell analysis
Single-cell RNA sequencing captures gene expression at the resolution of individual cells, enabling researchers to study the functional characteristics of individual cells at the molecular levels. This is an emerging field of study that provides insights into the heterogeneity and interactions between different cell types, as well as supporting the identification of key regulatory pathways and biomarkers that influence cellular behaviour in health and disease.
While traditional bulk analysis methods provide an average measurement of gene expression or protein activity across a population of cells, analysing cells at single-cell level enables researchers to identify rare cell types, capture cell to cell variability and discover unique cellular states that could prove critical for understanding cellular function in health and disease. This information may be invaluable for uncovering novel targets for bespoke therapeutic interventions, which in turn could drastically improve patient outcomes.
Spatial transcriptomics
This functional genomics tool works by mapping gene expressions within the spatial context of tissues, identifying where specific transcripts are located within a tissue section. This allows researchers to study gene activity, while also preserving the spatial organisation and architecture of the biological sample.
The process involves four key steps.
- Preparing the tissue by mounting a thin section onto a specially designed slide.
- Barcode capture, as the slide contains spatially encoded barcodes that capture mRNA from specific locations within the tissue.
- The captured mRNA is reverse-transcribed, sequenced and mapped back to spatial coordinates.
- Finally, gene expression data is overlaid with histological images or other spatial data to generate a spatially resolved transcriptomic map.
Spatial transcriptomics has a range of applications, from the identification of spatial patterns of gene expression in cancer cells to integrating gene expression with histological data for enhanced disease diagnosis and biomarker discovery.
Proteomics platforms
Used to study the proteome – which is the complete set of proteins expressed in a cell, tissue or organism at a specific time, proteomics platforms detect which proteins are present in a specific sample, measure the abundance of specific proteins, identify modifications such as phosphorylation that regulate protein activity and map how proteins interact to form complexes or pathways.
There are three types of proteomics:
Expression proteomics: which looks at the differences in protein expression levels between samples under various conditions, such as normal vs disease states, different developmental stages or environmental responses.
Functional proteomics: which looks at how proteins function and their role within interactions, enzymatic activities, modifications and cellular pathways.
Structural proteomics: which looks at the three-dimensional structures of proteins and their complexes to provide insights into function, stability, interactions and more.
Proteomics platforms are a crucial tool in functional genomics as they provide researchers with the tools and technologies needed for the comprehensive study of proteins, which are the central molecule responsible for most biological processes – at an accelerated pace and at the highest level of complexity.
Benefits of functional genomics to science and public health
Enhancing our understanding of the mechanisms by which the body functions and responds to external stimuli is critical for advancing our knowledge of health and disease. This growing body of knowledge is driving improvements in patient outcomes across several key areas.
Precision medicine
Precision medicine is a cutting-edge approach to disease prevention and treatment that takes into account the genetic and molecular makeup of an individual, as well as their environment and lifestyle, in order to make bespoke recommendations for therapies to optimise their health and wellbeing. It’s often referred to as personalised medicine.
Individuals exhibit unique genetic profiles, and precision medicine represents a shift away from the traditional, one-size-fits-all approach to treatment. While standard treatments may work for some patients, they often fail to deliver optimal outcomes for others and may not represent the most cost-effective solutions for healthcare systems. For example, a ‘standard’ treatment protocol may be ineffective for a particular patient due to their genetic composition. Instead of investing resources in a treatment unlikely to succeed, it is more efficient to direct patients towards a therapy that is better suited to their genetic profile from the outset.
This personalised approach is especially important for complex diseases, such as cancer and neurodegenerative disorder, which often involve multifactorial causes that influence disease progression. The integration of functional genomics into healthcare systems is instrumental in advancing precision medicine and enhancing patient outcomes.
Early detection of new threats
The importance of early detection in disease diagnosis is well known as a key factor in improved long-term survival rates and improved quality of life. Enhancing early detection rates relies heavily on a deeper understanding of the biological mechanisms underlying disease development. This is especially critical in cancers, where early diagnosis significantly expands the range of available treatment options and markedly improves patient survival outcomes.
The Generation Study, which is a world-leading initiative led by Genomics England in partnership with NHS England, is currently testing newborns for more than 200 rare genetic conditions. The study, which is the first of its kind, aims to screen up to 100,00 newborns across England with the aim of discovering whether delivering early treatments for those with rare genetic conditions could transform their care.
Pathogen genomics
Pathogen genomics is an area of study that looks at the genetic material of microorganisms that cause disease with the aim of being able to prepare for and respond to threats of infectious disease. Researchers can analyse genomes to identify harmful mutations or variations in a pathogen compared to known strains, enabling them to detect drug resistance or other important characteristics that could impact how we tackle such infectious diseases on a public health scale. Meanwhile, genomic data can also be used to effectively track the spread of infections, potentially supporting accurate outbreak predictions.
The prevalence of infectious diseases highlights the growing need for the development of effective vaccines and therapeutics. Pathogen genomics plays a pivotal role in facilitating the discovery and design of novel vaccines and treatments, addressing both active infections and providing potential protection against future outbreaks or emerging variants. Leveraging these genomic insights could significantly enhance our capacity for rapid and effective responses to infectious diseases on both national and global scales.
You can read more about the PKHSA’s new 5 year Pathogen Genomics Strategy here.
Functional genomics has the potential to revolutionise healthcare by providing an unprecedented, comprehensive understanding of gene interactions and functions within biological systems. By elucidating the biological mechanisms underlying disease susceptibility, progression and treatment response, functional genomics paves the way for precision medicine approaches tailored to individual genetic profiles.
With the insights provided by functional genomic technologies, healthcare providers can more accurately predict risks, diagnose disease earlier and recommend personalised interventions that optimise their outcomes. Simultaneously, functional genomics research can further drive the development of innovative therapies that target specific gene pathways, providing more hope for rare disease early intervention, treatment and better patient quality and length of life.
Moreover, the advancements enabled by functional genomics promise to accelerate preventive strategies for both genetic and infectious diseases, redefining the modern healthcare landscape and enhancing the efficacy of preventive health responses on a global scale.
