Tyler O'Neal, Staff Editor VISUALIZATION

Cambridge researcher develops cancer algorithm that flags genetic weaknesses in tumors

A new way to identify tumors that could be sensitive to particular immunotherapies has been developed using data from thousands of NHS cancer patient samples sequenced through the 100,000 Genomes Project. The MMRDetect clinical algorithm makes it possible to identify tumors that have 'mismatch repair deficiencies' and then improve the personalization of cancer therapies to exploit those weaknesses.

The study, led by researchers from the University of Cambridge's Department of Medical Genetics and MRC Cancer Unit, identified nine DNA repair genes that are critical guardians of the human genome from damage caused by oxygen and water, as well as errors during cell division.

The team used a genome editing technology, CRISPR-Cas9, to 'knock out' (make inoperative) these repair genes in healthy human stem cells. In doing so, they observed strong mutation patterns, or mutational signatures, which offer useful markers of those genes and the repair pathways they are involved in, failing.

The study, funded by Cancer Research UK and published today, indicates that these signatures of repair pathway defects are ongoing and could therefore serve as crucial biomarkers in precision medicine.

Senior author, Dr. Serena Nik-Zainal, a Cancer Research UK Advanced Clinician Scientist at Cambridge University's MRC Cancer Unit, said: "When we knock out different DNA repair genes, we find a kind of fingerprint of that gene or pathway being erased. We can then use those fingerprints to figure out which repair pathways have stopped working in each person's tumor, and what treatments should be used specifically to treat their cancer."

The new computer algorithm, MMRDetect, uses the mutational signatures that were identified in the knock-out experiments and were trained on whole-genome sequencing data from NHS cancer patients in the 100,000 Genomes Project, to identify tumors with 'mismatch repair deficiency' which makes them sensitive to checkpoint inhibitors, immunotherapies. Having developed the algorithm on tumors in this study, the plan now is to roll it out across all cancers picked up by Genomics England.

The breakthrough demonstrates the value of researchers working with the 100,000 Genomes Project, a pioneering national whole-genome sequencing endeavor.

Parker Moss, Chief Commercial and Partnerships Officer at Genomics England, said: "We are very excited to see such impactful research being supported by the 100,000 Genomes Project, and that our data has helped to develop a clinically significant tool. This is a fantastic example of how the sheer size and richness of the 100,000 Genomes Project data can contribute to important research.

"The outcomes from Dr. Nik-Zainal and her team's work demonstrate perfectly how quickly and effectively we can return value to patient care by bringing together a community of leading researchers through Genomics England's platform."

The study offers important insights into where DNA damage comes from in our bodies. Water and oxygen are essential for life but are also the biggest sources of internal DNA damage in humans.

Dr. Nik-Zainal said: "Because we are alive, we need oxygen and water, yet they cause a constant drip of DNA damage in our cells. Our DNA repair pathways are normally working to limit that damage, which is why, when we knocked out some of the crucial genes, we immediately saw lots of mutations."

"Some DNA repair genes are like precision tools, able to fix very specific kinds of DNA damage. Human DNA has four building blocks: adenine, cytosine, guanine, and thymine. As an example, the OGG1 gene has a very specific role in fixing guanine when it is damaged by oxygen. When we knocked out OGG1, this crucial defense was severely weakened resulting in a very specific pattern of guanines that had mutated into thymines throughout the genome."

To be most effective, the MMRDetect algorithm could be used as soon as a patient has received a cancer diagnosis and their tumor is characterized by genome sequencing. The team believes that this tool could help to transform the way a wide range of cancers are treated and save many lives.

Michelle Mitchell, Chief Executive of Cancer Research UK, said: "Determining the right treatments for patients will give them the best chance of surviving their disease. Immunotherapy in particular can be powerful, but it doesn't work on everyone, so figuring out how to tell when it will work is vital to making it the most useful treatment it can be.

"Our ability to map and mine useful information from the genomes of tumors has improved massively over the past decade. Thanks to initiatives like the 100,000 Genomes Project, we are beginning to see how we might use this information to benefit patients. We look forward to seeing how this research develops, and its possibilities in helping future patients."

Russian prof finds experimental proof for Zeeman spin-orbit coupling in antiferromagnetic

Tyler O'Neal, Staff Editor VISUALIZATION

A NUST MISIS professor was part of an international research team that has found evidence for the existence of the Zeeman spin-orbit coupling in antiferromagnetic conductors. This work may pave the way for the next generation of electronics. The study was published in npj Quantum Materials.

The electron possesses two fundamental properties: charge and spin. Conventional electronic devices use only the charge of electrons for information processing. In recent years, an enormous research effort has been focused on building fundamentally new electronic devices (often called "spintronic devices") that would specifically exploit spin properties in addition to charge degrees of freedom. Transfer from conventional electronics to spintronics technology opens the possibilities to construct devices with high storage density and fast operation. The two-component nature of spin-based systems makes them potentially applicable for quantum supercomputing.

The current effort in designing spintronic devices is focusing on understanding and making use of spin-orbit coupling, an interaction between the orbital angular momentum and the spin angular momentum of an individual particle, such as an electron. However, spin-orbit coupling occurring in many compounds is often weak or its emergence requires the use of heavy components. One way to overcome spin-orbit coupling-related challenges could be the use of antiferromagnetic. A spin-orbit coupling of an unusual nature termed Zeeman spin-orbit coupling is expected to manifest itself in a wide range of ferromagnetic conductors. Being proportional to the applied magnetic field, the coupling is tunable. Yet, experimental proof of this phenomenon has been lacking.

The collaboration of a NUST MISIS physicist with colleagues from Germany, France, and Japan produced, for the first time, experimental evidence of Zeeman spin-orbit coupling in two very different layered conductors: an organic antiferromagnetic superconductor, and a prominent electron-doped superconductor that belongs to the family of high-temperature cuprate superconducting materials. Obtained on two very different materials, the results of this work demonstrate the generic nature of the Zeeman spin-orbit coupling. In addition to its fundamental importance, the Zeeman spin-orbit coupling opens new possibilities for spin manipulation, much sought after in the current effort to harness electron spin for future spintronic applications. Laboratory equipment at the NUST MISIS Department of Theoretical Physics and Quantum Technologies CREDIT Sergey Gnuskov/NUST MISIS

"The Zeeman spin-orbit coupling can be significantly stronger than other known kinds of spin-orbit coupling, thus providing new avenues for the development of fundamentally new electronic devices," noted Pavel Grigoriev, Professor at the NUST MISIS Department of Theoretical Physics and Quantum Technologies, senior researcher at Landau Institute for Theoretical Physics.

SAIC acquires Koverse

Tyler O'Neal, Staff Editor VISUALIZATION

Science Applications International Corp. has entered into a definitive agreement to acquire Koverse, a software company that provides a data management platform enabling artificial intelligence (AI) and machine learning on complex, sensitive data.

Founded in 2012 by former U.S. intelligence community AI and high-volume data processing experts, Koverse is a 16-person, Seattle-based company that delivers scalable, secure, and high-performing solutions to federal and commercial customers. Koverse solves one of the most difficult and time-consuming challenges in developing AI tools: organizing structured and unstructured data from multiple sources based on a user’s individual attributes and permissions. This capability is essential for government and military organizations where data access requires various clearance levels, as well as regulated commercial industries such as healthcare, financial services, and pharmaceuticals.

Koverse’s unique mission expertise and secure platform are already used in the most demanding environments, and SAIC will bring this offering at scale to security-conscious customers across government.

“I am excited to welcome Koverse to team SAIC. Koverse’s impressive track record among its commercial and government customers coupled with its unique data management platform makes it a rare gem that enriches our current data modernization offerings,” said SAIC CEO Nazzic Keene. “We see many opportunities for Koverse across the federal defense, civilian, and intelligence communities. Together, we bring a passion for service, innovation, and integrity that will further drive digital transformation and innovation.”

“This transaction will drive faster innovation and enable organizations to transform how they use complex and sensitive data,” said Jon Matsuo, president and CEO of Koverse. “Joining forces with SAIC creates a direct channel to include Koverse as the underlying data platform in large, important pieces of the emerging defense and national intelligence community mission.”