An algorithm-based testing method which allows to accurately screen dozens of samples at once significantly reducing the cost, time and quantity of testing kits required has been developed by a group of Israeli researchers from Ben-Gurion University of the Negev, The National Institute for Biotechnology in the Negev (NIBN), the Open University and Soroka University Medical Center.
As explained to The Jerusalem Post by some of the scientists involved, the method has already in its first tests and is currently the object of an ongoing clinical trial at Soroka, while the Health Ministry just approved a pilot project in several centers across Israel which is set to commence soon. If everything goes as expected, the technique will then receive official approval.
“What we are doing right now is in many ways a direct extension of work we began many years ago,” Dr. Noam Shental from the Open University’s Department of Computer Science said. “In 2016 we published a paper presenting a mathematical framework for detecting carriers of rare mutations inside large populations. Six years later we managed to provide an experimental proof of concept by detecting mutations among a thousand plants of a specific kind of crop.”
Shental pointed out that the line of research was resumed after the beginning of the corona pandemic when he realized that the method could potentially be useful to identify coronavirus carries.
Dr. Tomer Hertz from BGU’s Shraga Segal Department of Microbiology, Immunology and Genetics explained that the testing system the researchers developed is based on the method of pooling.
Pooling was first used in the US army during the Second World War to test soldiers for syphilis: the sample of five soldiers was tested at the same time, if the results came out negative, all soldiers could be declared healthy, while only if the results were positive each man needed an individual test.
The coronavirus testing method just developed by the group pools together samples from 384 subjects. Each individual’s sample becomes part of six different pools. Special liquid dispensing robots are entrusted with generating them.
“In order to generate the pools you need to basically mix together different sets of samples, which is an error-prone job best done by robots,” Hertz told the Post, adding that in order to instruct the robots on how to mix the samples in order to identify the coronavirus carries they follow the theoretical design provided by Shental.
“The mixing is done in a way that once you receive the results from the pool, you already know which individuals are infected. It is a single-stage method, without the need for further rounds of testing,” he added. “This is one of the major novelties of our research and it is a key issue.”
Hertz said that preparing the pools originally required about five hours, but the time is reduced to one hour by using more advanced robots. After the pools are prepared, they are tested by diagnostics laboratories just like with normal samples.For 384 individuals, only 48 tests are required (one per every eight individuals).
Moreover, because the sample of each person is tested six times, it is more effective regarding the problem of false positives or false negatives which are often generated by mistakes or contaminations of the samples, as pointed out by Prof. Angel Porgador also from BGU’s Shraga Segal Department of Microbiology, Immunology and Genetics. Porgador is the coordinator of the BGU Coronavirus Task Force, under whose auspices the project was started.
The scientists have been working on the project for seven weeks. Experiments performed on the samples already tested by the Soroka laboratory gave the method a 100% success rate in detecting virus carriers. In the ongoing clinical trial with Soroka, samples from medical staff are being analyzed. So far, they have come out negative for all the 1,115 individuals tested, Hertz pointed out.
The testing method can be especially important as Israel and many countries are entering a new phase in containing the outbreak while restrictions are progressively being eased up, determining the need to perform mass testing on a large amount of individuals who are expected to mostly come out negative.
“The protocol that we developed that requires 48 tests for 384 individuals is suitable for what are called asymptomatic carriers, for testing a population with a low rate of infection, which is what is happening in Israel now,” Hertz explained.
“The number of tests required, in this case one of every eight people, and therefore the reduction in cost, depends on the carrier rate that it is aimed for. If the carrier rate gets lower, we can aim for a 24-fold reduction in cost, if it gets higher again in case of a new wave of infection, it could become only two-fold,” Porgador concluded.