The genomes of two distinct strains of the virus that causes the common lip cold sore, herpes simplex virus type 1 (HSV-1), have been identified within an individual person — an achievement that could be useful to forensic scientists for tracing a person’s travel history. The research also opens the door to understanding how a patient’s viruses influence the course of disease. The research by an international team was led by Moriah L. Szpara, assistant professor of biochemistry and molecular biology at Penn State University.

Most people harbour HSV-1, frequently as a strain acquired from their mothers shortly after birth and carried for the rest of their lives. The new discovery was made with the help of a volunteer from the United States. The research revealed that one strain of the HSV-1 virus harboured by this individual is of a European/North American variety and the other is an Asian variety — likely acquired during the volunteer’s military service in the Korean War in the 1950s.

“It’s possible that more people have their life history documented at the molecular level in the HSV-1 strains they carry,“ said Derek Gatherer, a lecturer in the Division of Biomedical and Life Sciences at Lancaster University in the United Kingdom and a member of the research team, which also includes scientists at Georgia State University, the University of Pittsburgh, and Princeton University.

Earlier research by the same team has demonstrated that the geographical origin of HSV-1 can be predicted, as well. Since Asian, African, and European/North American varieties of the virus exist, and the virus is often acquired early in life, the research implies that a personal strain of HSV-1 can reflect a person’s origin. Another implication is that two individuals who have identical strains of HSV-1 are more likely to be related than those who have different strains.

“Using similar genetic fingerprinting of HSV-1 could help flesh out a person’s life story, adding an extra layer of genetic information not provided by our genomes alone. Forensic virology could be on the way in the same way in which we use genetic fingerprinting of our human DNA to locate perpetrators at the scene of a crime and to help trace the relatives of unidentified bodies,’ Gatherer said.

“We’re working on better ways to sequence viral genomes from ever-smaller amounts of starting material, to allow identification and comparison of samples from diverse sources,” said Szpara, who also is affiliated with Penn State’s Huck Institutes of the Life Sciences. “Deep sequencing of viruses like HSV-1 will provide a better view of the viral genetic diversity that individuals harbor, and will provide valuable information about how that influences the course of disease.” Penn State

SCIEX University is a new online service launched by SCIEX for its mass spectrometry customers. Designed as a new way to master workflows, SCIEX University is powered by a robust learning management system and features a new look and feel. A personalized dashboard allows the user to see all training records, certifications and enrol in courses for online and instructor-led trainings. Learning programmes are customized for the user and hundreds of interactive courses are provided, enabling the user to participate at his/her own pace. The trainings will be in English initially followed by translations into Chinese and Japanese next year. The user interface on the website, however, can be changed into 24 different languages.

SCIEX University can be freely accessed at https://sciex.com/education

Thermo Fisher Scientific and HEALTH BioMed (HBM) have announced a collaboration to support HBM’s development of molecular diagnostic (MDx) kits for infectious disease and pharmacogenomics screening to serve the China market. Under the terms of a strategic agreement, HBM will submit all kits it develops on the Applied Biosystems 3500Dx Capillary Electrophoresis (CE) platform through the appropriate regulatory process with the China Food and Drug Administration (CFDA) following successful validation. “Our collaboration with Thermo Fisher Scientific will enable HBM to meet a critical need in the China market for a series of high accuracy kits designed to run on a single CE platform to improve human health outcomes,” said Jianwei Yu, Chairman and CEO of HEALTH BioMed. “Molecular diagnostics such as these can improve diagnosis and treatment strategies in hospital settings while also helping to decrease antibiotic abuse.” HBM intends to leverage its CE-based Advanced Fragment Analysis (AFA) technology and reagents, which are currently CE-IVD-and cFDA-marked as is the ABI 3500Dx platform, to develop multiple assays under its SureX brand of multiplex kits. HBM’s current offering for human papillomavirus (HPV) screening, for example, is designed to target 25 high- and low-risk markers with high sensitivity, specificity and low hands-on-time. Development of its pharmacogenomics kits under the agreement will be designed to further support precision medicine initiatives in the country. “As a world leader in serving science, we are proud to be an enabling partner to help HEALTH BioMed build its portfolio of molecular diagnostics designed to better manage human health in China,” said Mark Smedley, president of genetic sciences at Thermo Fisher. “We are committed to working with diagnostic partners around the world who share our vision to drive the era of precision medicine.”

www.thermofisher.com        www.nb-health.com/HGT

Genomic makeup of colorectal cancers predicts immune system ability to fight tumours
Colorectal cancers heavily bedecked with tumour-related proteins called neoantigens are likely to be permeated with disease-fighting white blood cells, researchers at Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard report in a new study. Because such an influx of white blood cells often signifies an immune system attack on cancer, the discovery will sharpen research into therapies that make tumours more vulnerable to such an attack.

The discovery was made by combining several data sets from patients in two large health-tracking studies, the Nurses’ Health Study and the Health Professionals Follow-up Study. Researchers first performed whole-exome sequencing on colorectal tumour samples from 619. This information was merged with data from tests of the immune system’s response to the tumours and with patient clinical data, including length of survival.      

“We were looking for genetic features that predict how extensively a tumour is infiltrated by lymphocytes [certain white blood cells] and which types of lymphocytes are present,” said study co-lead author, Marios Giannakis, MD, PhD, medical oncologist and clinical investigator at the Dana-Farber Gastrointestinal Cancer Treatment Center, and researcher at the Broad Institute of MIT and Harvard. “We found that tumours with a high ‘neoantigen load’ – which carry large quantities of neoantigens – tended to be infiltrated by a large number of lymphocytes, including memory T cells, which provide protection against previously encountered infections and diseases. Patients whose tumours had high numbers of neoantigens also survived longer than those with lower neoantigen loads.”

Neoantigens are deviant forms of protein antigens, which are found on normal cells. Genetic mutations often cause cancer cells to produce abnormal proteins, some of which get lifted to the cell surface, where they serve as a red flag to the immune system that something is amiss with the cell.        

“There can be hundreds or thousands of neoantigens on tumour cells,” Giannakis explained. “Only a few of these may actually provoke T cells to infiltrate a tumour. But the more neoantigens on display, the greater the chance that some of them will spark an immune system response.”

Therapies known as immune checkpoint inhibitors work by removing some of the barriers to an immune system attack on cancer. Although these agents have produced astonishing results in some cases, they’re generally effective only in patients whose immune system has already launched an immune response to cancer. By showing that tumours with high antigen loads are apt to be laced with T cells – and therefore to have provoked an immune response – the study may help investigators identify which patients are most likely to benefit in new clinical trials of immune checkpoint inhibitors.

The study’s genomic analysis of colorectal tumour samples also found several often-mutated genes that had not previously been strongly associated with the disease, including BCL9L, RBM10, CTCF, and KLF5. The discovery of their prevalence in colorectal cancer suggests that they may be valuable targets for new therapies.        Dana-Farber Cancer Institute

A new device for studying tumour cells can trap 10,000 individual cells in a single chip.

The technique, developed at the University of Michigan, could one day help screen potential cancer treatments based on an individual patient’s tumour and help researchers better understand so-called cancer stem cells. It also sheds light on a controversy: are large cells or small cells more likely to be cancer stem cells?

Cancer cells are not all the same, and one theory holds that no more than 5 percent of the cells in a tumour are cancer stem cells. These few may be the only cells capable of causing a relapse or metastasis.

‘Most normal cells will die if they are not anchored to something, but cancer stem cells can survive. They can become circulating tumour cells and come to another area of the body,’ said Euisik Yoon, professor of electrical engineering and computer science, and biomedical engineering.

The team led by Yoon designed and made a device that takes advantage of this ability in hopes of understanding cancer stem cells better: how to identify them, what causes them to grow or die, and how to target them with cancer treatments. Their chip contains up to 12,800 wells for catching individual cancer cells. The team tested the chip with breast cancer cells, donated by researchers in the U-M Comprehensive Cancer Center.

They mixed the cells into a solution and ran the liquid through tiny channels in a plastic chip. Each channel was lined with chambers for trapping single cells.

The chambers have small openings to a parallel channel, which creates a draft that draws cells in — sort of like the drain in a sink. Once a cell is trapped, it blocks that opening and stops the draft. This ensures that, most of the time, only one cell is pulled into each chamber.

The walls of the chamber are coated so that the cell can’t latch on. As a result, normal cells that can’t cause metastases die over the course of a few days, leaving behind just the cancer stem cells. These cells reproduce in their chambers, forming tiny floating colonies, or tumorspheres.

While the ability to isolate 10,000 individual cells is impressive, it wouldn’t be useful if the team had to manually record every one, as required by most devices that capture cancer cells. The key is their computer algorithm, capable of combing through the microscope images and assessing the size and number of cells in each well. The algorithm’s particular talent is identifying cells no matter whether they show up dimly or brightly in the microscope image.

‘Our method is special because we really want to enable the study of many cells at once,’ said Yu-Heng Cheng, a doctoral student in electrical engineering and computer science. ‘Cancer cells have many different appearances, and our algorithm recognizes them.’

University of Michigan www.mcancer.org/news/archive/cancer-stem-cells-new-method-analyzes-10000-cells-once