Discovery of a major technical error will improve epigenetics research

June 26, 2018, Linköping University
Colm Nestor, Assistant Professor, Linköping University. Credit: Linköping University

An error in one of the most widely used methods in epigenetics, DIP-seq, can cause misleading results, researchers at Linköping University, Sweden, have shown. This may have major significance in the research field, where Big Data and advanced methods of DNA analysis are used to study vast amounts of epigenetic data. The error can be corrected in previously collected DIP-seq data, which may lead to new discoveries from previous studies of human epigenetics. The results have been published in the journal Nature Methods.

In principle, every cell has the same DNA sequence. However, different cell types use very different groups of genes. This means that additional signals are required to control which genes are used in each individual cell type. One type of such signal consists of chemical groups directly attached to the DNA sequence. These chemical modifications of the DNA sequence form part of what is commonly called the . Epigenetic regulation of genes plays an important role in normal human development but is also associated with many diseases, such as cancer.

Researchers at Linköping University have now discovered a weakness in one of the most frequently used methods in epigenetic research, DNA immunoprecipitation sequencing (DIP-seq). Put simply, this is based on picking out the parts of the DNA that carry a particular epigenetic signal. For this, the researchers use various antibodies that recognise a specific chemical structure and bind to it. The antibodies are subsequently sorted and the sequences of the DNA that they have bound to are determined. Nestor's group noticed that certain epigenetic marks always occurred in the same place, even in DNA that shouldn't contain those epigenetic marks at all.

"Our discovery highlights the importance of experimental validation when using high-throughput technologies in research. Without such experimental rigour, pervasive errors can hide in plain sight, concealed by their consistency across studies," says Colm Nestor, Assistant Professor at the Department of Clinical and Experimental Medicine and lead investigator of the study.

By analysing more than 125 existing datasets Nestor's group revealed that DIP-seq commonly detected DNA sequences that did not have any . These false positives constitute 50-90 percent of the detected DNA regions, and the magnitude of the effect differs between different datasets."Now that we know about this error, it's extremely simple to subtract it away. Correcting for these errors will allow novel discoveries to be made from the wealth of epigenetics data already in the public domain" says Colm Nestor.

The researchers point out that the vast majority of results from previous studies are correct.

"We should continue to use these methods but correct for these errors by using appropriate experimental design," says Colm Nestor.

Explore further: Don't forget the 'epi' in genetics research, scientist says

More information: Antonio Lentini et al, A reassessment of DNA-immunoprecipitation-based genomic profiling, Nature Methods (2018). DOI: 10.1038/s41592-018-0038-7

Related Stories

Don't forget the 'epi' in genetics research, scientist says

April 5, 2018
In a review article published April 5 in the New England Journal of Medicine, scientist Andrew Feinberg, M.D., calls for more integration between two fields of DNA-based research: genetics and epigenetics.

​A new principle for epigenetic changes discovered

January 23, 2017
In a new study, researchers at Uppsala University have found evidence of a new principle for how epigenetic changes can occur. The principle is based on an enzyme, tryptase, that has epigenetic effects that cause cells to ...

New technique maps life's effects on our DNA

July 20, 2014
Researchers at the BBSRC-funded Babraham Institute, in collaboration with the Wellcome Trust Sanger Institute Single Cell Genomics Centre, have developed a powerful new single-cell technique to help investigate how the environment ...

Tea consumption leads to epigenetic changes in women

May 31, 2017
Epigenetic changes are chemical modifications that turn our genes off or on. In a new study from Uppsala University, researchers show that tea consumption in women leads to epigenetic changes in genes that are known to interact ...

Keeping egg cells fresh with epigenetics

January 1, 2018
Keeping egg cells in stasis during childhood is a key part of female fertility. New research published today in Nature Structural and Molecular Biology sheds some light on the role of epigenetics in placing egg cells into ...

Genetic guides to epigenetics

February 10, 2015
Dirk Schübeler and his group at the Friedrich Miescher Institute for Biomedical Research (FMI) identify determinants that set epigenetic marks along the genome. The new study, published in Nature, shows that genetic activity ...

Recommended for you

Why some human genes are more popular with researchers than others

September 18, 2018
Historical bias is a key reason why biomedical researchers continue to study the same 10 percent of all human genes while ignoring many genes known to play roles in disease, according to a study publishing September 18 in ...

Class of neurological disorders share 3-D genome folding pattern, study finds

September 18, 2018
In a class of roughly 30 neurological disorders that includes ALS, Huntington's Disease and Fragile X Syndrome, the relevant mutant gene features sections of repeating base pair sequences known as short tandem repeats, or ...

Researchers resolve decades-old mystery about the most commonly mutated gene in cancer

September 18, 2018
The most commonly mutated gene in cancer has tantalized scientists for decades about the message of its mutations. Although mutations can occur at more than 1,100 sites within the TP53 gene, they arise with greatest frequency ...

Study of one million people leads to world's biggest advance in blood pressure genetics

September 17, 2018
Over 500 new gene regions that influence people's blood pressure have been discovered in the largest global genetic study of blood pressure to date, led by Queen Mary University of London and Imperial College London.

Genetic mutations thwart scientific efforts to fully predict our future

September 17, 2018
Ever since the decoding of the human genome in 2003, genetic research has been focused heavily on understanding genes so that they could be read like tea leaves to predict an individual's future and, perhaps, help them stave ...

Gene therapy via skin protects mice from lethal cocaine doses

September 17, 2018
There are no approved medications to treat either cocaine addiction or overdose. Frequent users tend to become less and less sensitive to the drug, leading to stronger or more frequent doses. The typical result is addiction. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.