UEA Research Could Revolutionise Genomic Sequencing of Drug-Resistant Bacteria

New nanopore DNA sequencing technology on a device the size of a USB stick could be used to diagnose infection - according to new research from the University of East Anglia and Public Health England.

Researchers tested the new technology with a complex problem – determining the cause of antibiotic resistance in a new multi-drug resistant strain of the bacterium that causes Typhoid.

The results, published in the journal Nature Biotechnology, reveal that the small, accessible and cost effective technology could revolutionise genomic sequencing.

Current technology for ‘long read’ detailed genomic sequencing can be performed using expensive instrumentation (around £500,000). It is complex to perform, and generally only available in specialist laboratories.

The research team tested a new device called MinION, produced by Oxford Nanopore Technologies Ltd. The machine produces long sequencing reads using a different methodology that does not require optical imaging – but at a small fraction of the instrument cost (expected to be around £650 per device). These long reads are important when trying to determine where resistance genes are.

Researchers proved its utility by successfully mapping the multi-drug resistance genes in a strain called Salmonella typhi haplotype H58 – which has recently emerged globally.

They successfully pinpointed the exact spot in the chromosomal structure that is home to the genes which makes it drug-resistant, known as an antibiotic resistance island. The MinION took just 18 hours to produce the results, with similar accuracy to current technologies.

Lead researcher Dr Justin O’Grady, from UEA’s Norwich Medical School, said: “This type of technology will revolutionise the way that we characterise the rapid spread of emerging antibiotic-resistant infectious diseases.

“This analysis would previously have taken months using traditional methods, due to extensive post-sequencing lab-based analysis. By the time the results are available, they might well be irrelevant for clinical diagnostics and guiding public health interventions.

“This is the first published research in the world to demonstrate the huge potential of MinION sequencing to solve important and complex biological problems.

“Public health and clinical laboratories could soon have easy access to this rapid, cheap technology which, in combination with short read sequencing, is capable of providing fully assembled bacterial genomes. Further improvements to the system are likely to remove the need for short read sequence data.

“MinION technology could potentially enable bacterial identification, diagnosis of infectious diseases and detection of drug-resistance at the point of clinical need.

“This type of technology makes next generation sequencing accessible to scientists everywhere.”

The research was funded by Norwich Medical School, UEA. The international team included researchers from UEA, Public Health England, the University of Sassari in Italy, and the National Reference Centre for Salmonellae in Germany.

‘MinION nanopore sequencing identifies the position and structure of a bacterial antibiotic resistance island’ was published in the journal Nature Biotechnology on December 8, 2014.

Source: University of East Anglia

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World's Earliest Diagnostic Test for Ebola, Within 24 Hours of Infection

Marking a critical turning point in the fight against Ebola, a new Rapid Ebola Pre-Symptom Screening Test from IES Diagnostics, Inc. can accurately identify if someone is infected with the Ebola virus as early as 24 hours after they contract the virus. This is days to weeks before they are symptomatic and contagious. No other method can test for Ebola infection this early after the virus enters the body.

At this time, the Rapid Ebola Pre-Symptom Screening Test can detect the effects of virus infection within one day of exposure. Researchers anticipate that upcoming validation tests will show this test can detect Ebola effects even earlier--within a few hours of infection, or in less time than a transcontinental airplane trip.

Using a drop of blood, the Rapid Ebola Pre-Symptom Screening Test is designed to detect the unique combination of interferons (called a signature) produced immediately after cells are infected with the Ebola virus. Interferons are the body’s “first responder” proteins, produced only when cells are infected. The Rapid Ebola Pre-Symptom Screening Test can find the body’s interferon signature to Ebola even before the virus itself can be detected.

All other Ebola tests currently used or in development can only diagnose infection when the virus has replicated to levels high enough to be directly detected--typically 8-21 days after infection. At that stage, a person may already be contagious.

Delaying an early, accurate diagnosis can lead to lengthy--and often unnecessary—quarantine periods. Conversely, it can prevent quarantines where needed. For example, the limited sensitivity of current Ebola tests may provide “false negative” results. That may lead an infected person to forego quarantine. This action may unintentionally spread this deadly disease as well as delay an infected individual’s early treatment – significantly decreasing their overall chance of survival. The Rapid Ebola Pre-Symptom Screening Test is a vital tool for detecting Ebola infection earlier, limiting the spread of infection while allowing those infected to be treated earlier.

Key scientific facts about the new Rapid Ebola Pre-Symptom Screening Test:

• Once validation tests are completed, the Rapid Ebola Pre-Symptom Screening Test can be readily implemented in the field using existing methods. IES Diagnostics’ test uses PCR (polymerase chain reaction), the same test approach currently used to detect Ebola virus RNA. Also, clinical samples are collected, stored and transported the same way those from antibody Ebola tests are.
• This pivotal interferon signature screening tool is the only test in the world that can diagnose a person’s response to Ebola infection several days before viral RNA is measurably detected.
• Tests identifying Ebola antibodies through protein detection are less sensitive than IES Diagnostics’ interferon signature testing. Antibody detection tests also are limited in that they must be used when antibody levels are robust enough for detection—days to weeks following exposure. Additionally, antibody tests are surrogate markers of exposure, and do not necessarily indicate active infection.

“Interferon response is the ideal rapid diagnostic tool since it appears immediately after cells are infected with a virus,” explains Ronald Jubin, PhD, molecular biologist and Founder/President of IES Diagnostics, Inc. “Because each response is virus-specific, we can tell if someone has Ebola based on the interferon signature that appears.”

“Being able to test people long before they are contagious is a critical turning point in the fight against Ebola,” Jubin says. “Our ultimate target is to develop a handheld device capable of producing a result within minutes of infection.”

IES Diagnostics’ interferon signature-based technology was developed collaboratively with the US Food and Drug Administration (FDA) and licensed exclusively to IES Diagnostics, Inc. by the US National Institutes of Health (NIH).

IES Diagnostics, Inc. is a molecular diagnostics company in the United States working at the forefront of companion diagnostics and personalized medicine. Its proprietary, patented assay is the first and only test capable of detecting and quantifying all of the unique interferon signatures for any disease or virus with an interferon reaction. Interferon-associated diseases include viral infections, auto-immune diseases (such as lupus, rheumatoid arthritis and multiple sclerosis, among many others) and cancers. With IES Diagnostics’ interferon signature assay, science and medicine have a sensitive, accurate tool to detect and diagnose disease and infection earlier. These signatures also provide disease-specific knowledge that can lead to targeted, effective treatment options with fewer side effects.

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