“Information theory” adopted to help scientists find oncogenes

An illustration of the research concept that DNA methylation codes can be analyzed using information theory represented by the strings 0 and 1. This analysis helps researchers understand the epigenetic landscape of cancer (painted in blue) and identify the genes that regulate this landscape (shown as strings and posts below the blue landscape). It has been). Credits: Kate Zvorykina (Ella Maru Studio), Designs: Michael Koldobskiy and Andrew Feinberg, Johns Hopkins Medicine

Scientists at the Johns Hopkins Medicine and Johns Hopkins Skinmel Cancer Center have developed a well-known field of mathematics designed primarily to study ways to measure, store, and share digital and other forms of information. It states that it has found an important genetic cause in the development of acute lymphocytic leukemia (ALL).

ALL is the most common form of childhood leukemia, affecting an estimated 3,000 children and teens each year in the United States alone.

Specifically, Johns Hopkinsteam uses “information theory” to apply an analysis that relies on strings of 0s and 1s (binary systems of symbols common to computer languages ​​and codes) to apply an analysis of a particular process. You have identified a variable or result. In the case of human cancer biology, scientists have focused on an intracellular chemical process called DNA methylation. In this process, specific chemical groups attach to the region of the gene that leads to the on / off switch of the gene.

“This study shows how the mathematical language of cancer can help us understand how cells should behave and how changes in that behavior affect our health. “, Whiting School of Engineering and Bloomberg School of Public Health. Feinberg, the founder of the field of cancer epigenetics, discovered changes in cancer DNA methylation in the 1980s.

Feinberg and his team say finding cancer driver genes using information theory may be applicable to a wide variety of cancers and other illnesses.

Methylation is now recognized as one way in which DNA can be altered without altering the genetic code of the cell. When methylation fails in these epigenetic phenomena, certain genes turn on or off abnormally, causing uncontrolled cell growth and cancer.

“Most people are familiar with genetic alterations in DNA, mutations that alter the DNA sequence. These mutations are like the words that make up a sentence, and methylation is the punctuation of the sentence. It’s like, and provides pauses and pauses when reading. ” Feinberg. With Dr. John Goussias and Michael Cordobski, professors of electrical and computer engineering at Johns Hopkins University, to find new and more efficient ways to read and understand epigenetic code modified by DNA methylation. I cooperated. , MD, Ph.D. , Pediatric Oncology, Associate Professor of Oncology at Johns Hopkins Kimmel Cancer Center.

“We wanted to use this information to identify genes that promote the development of cancer even if the genetic code is not mutated,” says Koldobskiy.

The findings, led by Feinberg, Koldobskiy and Goutsias, were released on April 15th. Nature Biomedical Engineering.

Koldobskiy says that methylation at specific gene positions is binary (no methylation or methylation), and these 0 and 1 systems are used to represent computer codes and instructions. It explains that it can represent the difference between.

For this study, the Johns Hopkins team analyzed DNA extracted from bone marrow samples from 31 children newly diagnosed with ALL at Johns Hopkins Hospital and Texas Children’s Hospital. They sequenced the DNA and identified the methylated and unmethylated genes throughout the genome.

Newly diagnosed leukemia patients have billions of leukemia cells in their bodies, says Koldobskiy.

By assigning zeros and ones to methylated or unmethylated pieces of the genetic code and recognizing patterns of methylation using information theory and computer program concepts, scientists are consistent in leukemia and those patients. I was able to find a region of the methylated genome. No cancer.

They also looked at the genomic regions of leukemia cells that were more randomly methylated compared to the normal genome. This is a signal to scientists that these spots may be specifically associated with leukemia cells compared to normal ones.

One gene, called UHRF1, stood out among other gene regions of leukemia cells that differed in DNA methylation compared to the normal genome.

“The discovery of this gene was a big surprise. It has been suggested to be associated with the prostate and other cancers, but it has never been identified as the cause of leukemia,” Feinberg said.

In normal cells, the protein product of the UHRF1 gene provides a biochemical bridge between DNA methylation and DNA packaging, but scientists are deciphering exactly how genetic alterations contribute to cancer. not.

Experiments by Johns Hopkins team have shown that laboratory-grown leukemia cells that lack the activity of the UHRF1 gene are unable to self-replicate and perpetuate additional leukemia cells.

“Leukemia cells aim to survive. The best way to survive is to alter epigenetics in many genomic regions so that no matter what kills the cancer, at least some will survive. That’s what Koldobskiy says.

ALL is the most common childhood cancer, and Koldobskiy says decades of research into different treatments and the order of those treatments has helped clinicians treat most of these leukemias. However, recurrent disease remains the leading cause of cancer death in children.

“This new approach could lead to a more rational way to target this and perhaps many other forms of cancer-causing changes,” says Koldobskiy.

The Johns Hopkins team plans to use information theory to analyze methylation patterns in other cancers. They also plan to determine whether epigenetic changes in URFH1 are associated with treatment resistance and disease progression in pediatric leukemia patients.

Cancer leaves a common fingerprint in DNA

For more information:
Michael A. Koldobskiy et al, Convergence of Genetic and Epigenetic Drivers of Pediatric Acute Lymphoblastic Leukemia Identified by Information-Theoretic Analysis, Nature biomedical engineering (2021). DOI: 10.1038 / s41551-021-00703-2

Courtesy of Johns Hopkins University School of Medicine

Quote: The “Information Theory” (April 20, 2021) adopted to help scientists find oncogenes is https: // Obtained from genes.html on April 20, 2021

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“Information theory” adopted to help scientists find oncogenes

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