Why It Matters

Some examples of areas of research in which the contribution of CEGX’s technology is under active investigation are shown below.

Early Diagnosis and Disease Monitoring

It is undeniable that detecting and treating cancer at its earliest stage saves lives. Early detection provides the best possible outcomes for patients, it alleviates morbidity and increases survival. Still, around half of cancer diagnoses are made at an advanced stage 1. In their review, Crosby et al. report on the current research challenges for early detection strategies.

Identifying biomarkers sensitive and specific enough to detect early cancers in a high background of normal cells is an important goal. Liquid biopsy, involving profiling of tumour derived DNA (ctDNA) circulating in the patient’s blood, is very promising for early detection. It affords a profile of the tumour, without the need for invasive surgical procedures. As well as early detection, liquid biopsies are invaluable for treatment monitoring; for example, monitoring recurrent disease, the emergence of drug resistance and subtype switching.1,2


Using liquid biopsy to detect early cancers has technical challenges. For instance, ctDNA is present in low quantities and requires ultra-sensitive methods for sequencing and analysis. The addition of DNA epigenetic letters increases sensitivity for detection at early stage and is informative of the tissue of origin of ctDNA indicating the anatomical location of the tumour 2,3. Large scale clinical trials, evidencing the utility of cancer associated DNA methylation markers identified in blood, are currently underway in the UK (NCT103934866) and US (NCT04241796).

Our collaborators and early access customers are investigating the contribution of CEGX technologies to early cancer detection and disease monitoring

New Therapeutic Approaches and Ageing

DNA epigenetic letters provide an additional regulatory layer that plays an important role in cell differentiation and fate.  DNA methylation age as calculated from DNA methylation levels at a set of CpG sites is highly correlative with chronological age in humans and predictive of all-cause mortality4. The potential to quantify biological age and modify it has sparked extensive research 5. There are clear applications for all disease of ageing including Alzheimer’s disease, osteoporosis, type II diabetes and chronic heart disease. It was recently shown that stable reversal of DNA methylation changes accompanied restoration of cells to a youthful configuration6. Moreover, the genetic letters interact with environmentally-driven epigenetic letters to influence the ability of cells to rejuvenate6,7. CEGX’s sequencing technologies, that measure phased genetic and epigenetic letters from biosamples, are facilitating research in this exciting field.

Precision Medicine

Most treatment is variably beneficial for individual patients with the same disease. Precision medicine aims to predict whether a treatment will deliver benefit to an individual patient. Disease, and also response to treatment, is the result of the interaction an individual’s genetics with their environment. The use of DNA genetic letter data is well established for treatment guidance and selection through companion diagnostics or comprehensive genomic profiling. However, these approaches ignore the environmental component of disease aetiology.

Dynamic epigenetic letters change with environment, cellular composition8 and disease treatment.  It is becoming increasingly evident that determining genetic and epigenetic information in the same sample enables better identification of disease relevant biomarkers9 as genetic and environmental aspects of disease are incorporated. Through the use of multi-omic technologies the causal mechanism of the biomarkers in the disease  can be explored and understood10. CEGX’s technology is enabling researchers to advance our understanding of genetic-epigenetic correlates to disease. As our understanding of these mechanisms increases, they can be used in a diagnostic setting to help guide the most appropriate treatment.

  1. Crosby, D. et al. Early detection of cancer. 11 (2022).
  2. Lo, Y. M. D., Han, D. S. C., Jiang, P. & Chiu, R. W. K. Epigenetics, fragmentomics, and topology of cell-free DNA in liquid biopsies. Science 372, eaaw3616 (2021).
  3. Klein, E. A. et al. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. S0923-7534(21)02046–9 (2021) doi:10.1016/j.annonc.2021.05.806.
  4. Lu, A. T. et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging 11, 303–327 (2019).
  5. Bell, C. G. et al. DNA methylation aging clocks: challenges and recommendations. Genome Biol. 20, 249 (2019).
  6. Chondronasiou, D. et al. Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming. Aging Cell 21, e13578 (2022).
  7. Skelly, D. A. et al. Mapping the Effects of Genetic Variation on Chromatin State and Gene Expression Reveals Loci That Control Ground State Pluripotency. Cell Stem Cell 27, 459-469.e8 (2020).
  8. Zhu, T. et al. A pan-tissue DNA methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution. Nat. Methods 19, 296–306 (2022).
  9. Hawe, J. S. et al. Genetic variation influencing DNA methylation provides insights into molecular mechanisms regulating genomic function. Nat. Genet. 54, 18–29 (2022).
  10. Ahmed, M. et al. CRISPRi screens reveal a DNA methylation-mediated 3D genome dependent causal mechanism in prostate cancer. Nat. Commun. 12, 1781 (2021).