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New technologies are revolutionising scientists’ approach to cancer genome sequencing from diagnosis to treatment. Discover the role that lab automation plays.
What is cancer genome sequencing?
Cancer genome sequencing is the DNA (or RNA) sequencing of the whole, or regions of the genome of cancer cells. The first cancer whole-genome sequence was published in 2008 by Ley et al., of an acute myeloid leukaemia(1). Genome sequencing has opened up a world of opportunities for clinicians to improve the diagnosis of cancers and develop precision treatments targeted to individual patients.
In comparing the genome sequence of cancer cells to normal, healthy tissues to identify mutations, researchers can better understand the molecular biology behind the cause of cancers and their growth and assess individual patient prognosis and how likely they are to respond to certain treatments.(2)
Cancer genomics technologies
Cancer genome sequencing can detect both germline (inherited) and somatic (acquired) mutations. Next-generation sequencing (NGS) enables high throughput screening to rapidly generate genome sequences. This information allows for the development of novel therapeutics.
These precision therapies cause fewer side effects than chemotherapy, due to their specific targeting of proteins characteristic to genetic alterations. In addition, integrating proteomic profiles alongside genomic sequencing, known as proteogenomics, can be used to aid the understanding of cancers at a molecular level.
Genomic sequencing has improved research into the evolution of cancers, enabling the tracking of tumour development through genome analysis and tumour sampling. For example, TRACERx is a study of non-small cell lung cancer patients conducted in 2014, in which they tracked genetic mutations during cancer’s development and monitored patients’ health outcomes(3 – 5).
Challenges of cancer genome sequencing
Sample quality
One of the primary challenges for effective cancer genome sequencing is the efficient use of high-quality samples. The mutations involved in tumour growth are often very specific. Testing is required to search for many different genetic alterations, and biological samples can be rapidly exhausted. Therefore, procuring enough high-quality tumour samples can be problematic. Alternative extraction methods are currently under development, such as liquid biopsy, as non-invasive diagnostic tests are typically conducted using blood.
Data rationalisation
Sequencing a cancer genome produces vast amounts of data. Analysing this data requires significant computational resources and sophisticated bioinformatics tools. Moreover, cancer genomes often contain complex structural variations, copy number variations, and a high mutation burden, making data interpretation challenging.
Integrating genomic data with other omics data (e.g. transcriptomic, proteomics) to get a comprehensive view of the cancer’s biology is complex and combining genomic data with clinical data to make informed decisions is still an evolving area.
While behavioural, biophysical, and biomedical data has significantly enhanced our understanding of public health issues and expanded the range of possible responses, much of that data was not originally collected for scientific purposes, and so those developing treatments face the challenge of rationalising complex data sets.
Looking ahead: the role of lab automation in cancer genomics
Genomics provides a wealth of opportunities to improve the diagnosis and treatment of cancers. However, the next generation of cancer genomics requires a ‘work smarter, not harder’ approach with lab automation at the forefront.
- Improving the quality and accessibility of data
Newer automation like LINQ can collect more data points than ever before while transferring that information—from an entire experimental tech stack—into any data lake for immediate contextualisation of experiment results, meaning they can be repeated and reproduced.
- Removing bottlenecks
There are many bottlenecks in the process of NGS sequencing that can limit workflow. Sample preparation is a laborious and time-consuming step of NGS, susceptible to human-induced error, for example, while labs are struggling to hire enough lab staff to maintain an efficient workflow, with researcher’s time consumed in low-value processes.
Automating sample preparation of libraries can free up valuable team members for higher-value tasks.6,7
- Facilitating scale
Lab automation can unlock large-scale experimentation capabilities without the need for additional staff in a way that ensures more control over variables, easier access to conditional data, and the ability to increase throughput by extending working hours, increasing the speed of tasks, and parallelising touchpoints for maximum lab efficiency.
Genomics labs need to start adopting automation at the workflow, lab, and ultimately network levels to reduce the cost of genome sequencing, achieve the required cancer diagnostic throughput, and to get therapeutics to market faster.
LINQ by Automata
LINQ is a next-generation lab automation platform that can eliminate manual interactions and fully automate your genomic workflows, end to end. Explore how automation could revolutionise your lab’s capabilities: book an exploration call today.
We’re partnering with the NHS on genomic testing
For the first time in the UK, robotic technology is being used to support genomic testing for cancer patients following a partnership between The Royal Marsden NHS Foundation Trust and Automata.
The innovative installation will double the Trust’s genomics testing capacity and expand the range of tests.
References
1. Fletcher, M. Sequencing the secrets of the cancer genome. Nature Research (2020) doi:10.1038/d42859-020-00075-8.
2. Nogrady, B. How cancer genomics is transforming diagnosis and treatment. Nature 579, S10–S11 (2020).
3. Kelly, A. Key genomic technologies of 2020: treatments old and new. Genomics Education Programme https://www.genomicseducation.hee.nhs.uk/blog/key-genomic-technologies-of-2020-treatments-old-and-new/ (2021).
4. Genomics, F. L. & Mobley, I. Cancer Genomics: From Diagnosis to Treatment. Front Line Genomics https://frontlinegenomics.com/cancer-genomics-from-diagnosis-to-treatment/ (2021).
5. Cancer genome research and precision medicine – NCI. https://www.cancer.gov/about-nci/organization/ccg/cancer-genomics-overview (2015).
6. Muscarella, L. A. et al. Automated Workflow for Somatic and Germline Next Generation Sequencing Analysis in Routine Clinical Cancer Diagnostics. Cancers (Basel) 11, 1691 (2019).7. Keefer, L. A. et al. Automated next-generation profiling of genomic alterations in human cancers. Nat Commun 13, 2830 (2022).
More about the NHS GLH network
The NHS Genomic Laboratory Hubs (GLHs) are a network of laboratories in the United Kingdom established to deliver genomic testing and services as part of the National Health Service (NHS). These hubs play a critical role in integrating genomics into routine healthcare, allowing for more precise and personalised medical treatments.
The NHS Genomic Medicine Service (NHS GMS) is the division of the NHS dedicated to utilising genomic technology and science to enhance the health of the population.
- Genomic testing and analysis
GLHs provide comprehensive genomic testing for a variety of conditions, including rare diseases, inherited conditions, and cancers.
They use advanced technologies like whole-genome sequencing, exome sequencing, and targeted gene panels to identify genetic variants.
- Personalised medicine:
By identifying genetic mutations and variations, GLHs help tailor treatments to individual patients, improving outcomes and reducing adverse effects.
This approach is particularly beneficial in oncology, where targeted therapies can be more effective based on the genetic profile of a tumor.
- Research and development:
GLHs contribute to genomic research, collecting and analysing data to improve understanding of genetic diseases.
They collaborate with academic institutions, research organisations, and pharmaceutical companies to advance genomic medicine.
- Education and Training:
These hubs also focus on educating healthcare professionals about genomics, ensuring they have the necessary skills and knowledge to incorporate genomic information into patient care.
- Data management and sharing:
GLHs manage large amounts of genomic data, ensuring it is securely stored and shared appropriately to facilitate research and clinical care.
They follow stringent data governance and privacy standards to protect patient information.
Rare Diseases:
GLHs have significantly improved the diagnosis of rare genetic disorders, often providing answers to patients who have had long diagnostic journeys.
Early and accurate diagnosis can lead to better management and treatment of these conditions.
Cancer Treatment:
Genomic profiling of tumors helps in selecting the most effective treatments, avoiding unnecessary therapies, and improving survival rates.
It also aids in identifying patients for clinical trials of new targeted therapies.
Preventive Care:
Identifying genetic predispositions to certain conditions can enable preventive measures and early interventions, reducing the burden of disease.
Automata has partnered with The Royal Marsden NHS Foundation Trust to double the Trust’s genomics testing capacity and expand the range of tests it can perform within its existing laboratory space using Automata’s product, LINQ.
With increased capacity thanks to LINQ automation, the hospital will not only be able to process more somatic tests but also launch new genetic – or cancer germline – testing. This type of genomic testing identifies inherited genetic changes that can increase risk of cancer and, for patients with the disease, can also be used to identify the right treatments. It will primarily test for mutations in the BRCA genes, which can impact risk of various cancers including breast and ovarian.
The new testing capability will support research into genetics and cancer, such as the BRCA-DIRECT mainstreaming pilot. Led by Dr Clare Turnbull, Professor of Translational Cancer Genetics at The Institute of Cancer Research, London, and Consultant in Clinical Cancer Genetics at The Royal Marsden NHS Foundation Trust, with funding from the NHS Cancer Programme Small Business Research Initiative (SBRI) the project is aiming to boost BRCA gene testing access for breast cancer patients and their family members through a simple, digital pathway.
The new robotic facility is housed in the Sharjah Clinical Genomics Laboratory in the National Institute for Health and Care Research (NIHR) Centre for Molecular Pathology (CMP) at The Royal Marsden. The NIHR CMP is supported by funding from the National Institute for Health Research Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research, London, and The Royal Marsden Cancer Charity.
The Royal Marsden opened its doors in 1851 as the world’s first hospital dedicated to cancer diagnosis, treatment, research and education.
Today, together with its academic partner, The Institute of Cancer Research (ICR), it is the largest and most comprehensive cancer centre in Europe seeing and treating over 59,000 NHS and private patients every year. It is a centre of excellence with an international reputation for groundbreaking research and pioneering the very latest in cancer treatments and technologies.
The Royal Marsden, with the ICR, is the only National Institute for Health and Care Research Biomedical Research Centre for Cancer. This supports pioneering research work carried out over a number of different cancer themes.
The Royal Marsden Cancer Charity raises money solely to support The Royal Marsden, a world-leading cancer centre. It ensures Royal Marsden nurses, doctors and research teams can provide the very best care and develop life-saving treatments, which are used across the UK and around the world.
From funding state-of-the-art equipment and ground-breaking research, to creating the very best patient environments, The Royal Marsden Cancer Charity will never stop looking for ways to improve the lives of people affected by cancer.
