Researchers expect their test to reduce diagnostic time in clinical settings and help identify carriers of the diseases
Clinical laboratories have always been at the forefront of helping families battle rare diseases. But such testing is sometimes invasive and expensive. Now there’s a new blood test that is minimally invasive and rapidly detects thousands of rare genetic diseases in infants and children using a mere 1ml of blood.
Developed at the University of Melbourne and Murdoch Children’s Research Institute in Australia, the test rapidly detects abnormalities using proteomics to simultaneously analyze the pathogenicity of thousands of gene mutations that cause rare genetic illnesses.
The single-drop blood test sequences proteins present in the genes rather than the genes themselves to discover how genetic changes within those proteins affect function and lead to disease. According to the scientists, the test is cost-effective, potentially eradicates the need for other functional tests, and may be applicable to thousands of different diseases. Results of the test are typically available within three days, providing patients with earlier access to any available treatments.
“A recent study carried out in collaboration with the Melbourne School of Population and Global Health revealed that implementing our test in a clinical setting would have a similar cost to that of the current test used to diagnose rare mitochondrial disease, with the advantage that our test can potentially diagnose thousands of other diseases,” said the study’s co-author, Daniella Hock, PhD, a research fellow in clinical proteomics in the department of biochemistry and pharmacology at the University of Melbourne, in a news release.
“Our new test can identify more than 8,000 proteins in peripheral blood mononuclear cells covering more than 50% of known Mendelian and mitochondrial disease genes, as well as enable us to discover new disease genes,” said Daniella Hock, PhD, research fellow in clinical proteomics, department of biochemistry and pharmacology at the University of Melbourne, in the news release. (Photo copyright: Mito Foundation.)
Identifying Disease Carriers
The researchers also performed blood analysis on the parents to help identify the carriers of genetic illnesses and possibly develop reproductive methods to avoid the occurrence of those diseases in future pregnancies.
“When the test is also performed on blood samples from parents we call it trio analysis. In recessively inherited conditions, this helps considerably in differentiating between carriers, who only have one copy of the defective gene, and the affected individual, who carries two copies,” Hock said. “Moreover, the use of familial samples for trio analysis greatly improves the differentiation between carrier and affected individuals with higher confidence, and that has exceeded our initial expectations. We believe that the use of this test in clinical practice will bring considerable benefits to patients, their families, and healthcare systems by reducing the diagnostic time.”
Getting the Right Diagnosis
There are more than 7,000 types of categorized rare diseases which affect approximately 300 to 400 million people worldwide. These diseases are caused by genetic mutations that exist in more than 5,000 known genes. The new test focuses on rare genetic illnesses known as monogenetic disorders, such as cystic fibrosis and mitochondrial disease, that are caused by a single gene alteration or mutation.
According to the National Organization for Rare Disorders, 25 to 30 million Americans are living with a rare disorder. A condition is categorized as rare if it affects less than 200,000 individuals.
Global Genes states on its website that 400 million people worldwide suffer from a rare disease and half of those diagnosed are children. It also states that 80% of those diseases are genetic and 95% of rare diseases lack a treatment approved by the US Food and Drug Administration.
“One of the hardest things for patients with rare diseases is getting the right diagnosis,” said Sharon Barr, PhD, executive vice-president of biopharmaceuticals research and development at AstraZeneca Rare Disease, in an interview with STAT News.
On average, it takes about five years to accurately diagnose a rare disease patient. During that period, that patient sees various specialists, undergoes difficult tests, and potentially faces the wrong diagnosis, Barr said.
Initial results stemming from the new clinical laboratory test are encouraging, but more research and clinical trials are needed before the test can be used on a widespread level.
Royal College of Pathologists of Australia says the pandemic is ‘suppressed’ to ‘intermittent’ outbreaks, thanks to the dedication of thousands of pathologists, medical scientists, and laboratory professionals
COVID-19 efforts in Australia have achieved a milestone. Pathology laboratories there have performed more than 12 million SARS-CoV-2 tests since the pandemic began. That is an impressive feat and is equal to about half the country’s population of 25.4 million people.
“It is an incredible feat,” they continued. “Australia’s current position of having effectively suppressed the virus to intermittent outbreaks owes much to the year-long dedication and ingenuity of 35,000 pathologists, medical scientists, lab technicians, couriers, phlebotomists, and ancillary personnel.”
Australia Pathology Society Recognizes Accomplishments
Furthermore, Graves and Bott wrote, pathology in Australia deserves recognition for these pandemic-related accomplishments, among others, as well:
Australia launched drive-through COVID-19 testing clinics even before the pandemic was declared by the World Health Organization (WHO).
An RCPA quality assurance program for lab COVID-19 testing was the first of its kind to start worldwide, and it became a model for other countries.
Australia’s pathology labs were fast to develop in-house test kits once they had the genome sequence for the SARS-CoV-2 coronavirus.
Quick Responses to COVID-19 in the Land Down Under
The Doherty Institute (a joint venture of the University of Melbourne and the Royal Melbourne Hospital) offers research, teaching, public health and reference lab services, diagnostics, and clinical care for infectious diseases and immunity.
After receiving the patient sample on Jan. 24, 2020, institute scientists were the first outside China to grow the coronavirus in cell culture, noted a University of Melbourne news release.
“We’ve planned for an incident like this for many, many years, and that’s really why we were able to get an answer so quickly,” Dr. Mike Catton (above), Co-Deputy Director, Doherty Institute and Director of the Victorian Infectious Diseases Reference Laboratory (VIDRL), said in the news release. (Photo copyright: ABC News.)
Doherty Institute researchers also were first to report on immune response to COVID-19, according to a second news release.
“When COVID-19 emerged, we already had ethics and protocols in place so we could rapidly start looking at the virus and immune system in great deal,” Dr. Irani Thevarajan, Infectious Disease Physician, Doherty Institute, Royal Melbourne Hospital, said in the second news release.
“Our study provides novel contributions to the understanding and kinetics of immune responses during a non-severe case of COVID-19. This patient did not experience complications of respiratory failure or acute respiratory distress syndrome, did not require supplemental oxygenation, and was discharged within a week of hospitalization, consistent with non-severe but symptomatic disease,” Thevarajan and co-authors wrote in Nature Medicine.
Drive-Through COVID-19 Testing Sites in Australia
Also impressive was Australia’s launch of drive-through COVID-19 testing on March 9, 2020, before the pandemic was declared by WHO on March 11.
The COVID-19 testing site in Adelaide, South Australia, was “believed to be a first for the country’s public health system,” ABC News reported.
Public Recognition for Medical Laboratories has Global Reach
The COVID-19 response and scientific contributions by pathology laboratory scientists and researchers in Australia are noteworthy. It is also significant that Australia’s pathology professional society sought recognition for medical laboratory workers by detailing their accomplishments during the pandemic and sharing them in media with national and global reach.
Protecting patient privacy is of critical importance, and yet researchers reidentified data using only a few additional data points, casting doubt on the effectiveness of existing federally required data security methods and sharing protocols
Therefore, recent coverage in The Guardian which reported on how easily so-called “deidentified data” can be reidentified with just a few additional data points should be of particular interest to clinical laboratory and health network managers and stakeholders.
“We found that patients can be re-identified, without decryption, through a process of linking the unencrypted parts of the record with known information about the individual such as medical procedures and year of birth,” Culnane stated in a UM news release. “This shows the surprising ease with which de-identification can fail, highlighting the risky balance between data sharing and privacy.”
In a similar study published in Scientific Reports, Yves-Alexandre de Montjoye, PhD, a computation private researcher, used location data on 1.5 million people from a mobile phone dataset collected over 15 months to identify 95% of the people in an anonymized dataset using four unique data points. With just two unique data points, he could identify 50% of the people in the dataset.
“Location data is a fingerprint. It’s a piece of information that’s likely to exist across a broad range of data sets and could potentially be used as a global identifier,” Montjoye told The Guardian.
The problem is exacerbated by the fact that everything we do online these days generates data—much of it open to the public. “If you want to be a functioning member of society, you have no ability to restrict the amount of data that’s being vacuumed out of you to a meaningful level,” Chris Vickery, a security researcher and Director of Cyber Risk Research at UpGuard, told The Guardian.
This privacy vulnerability isn’t restricted to just users of the Internet and social media. In 2013, Latanya Sweeney, PhD, Professor and Director at Harvard’s Data Privacy Lab, performed similar analysis on approximately 579 participants in the Personal Genome Project who provided their zip code, date of birth, and gender to be included in the dataset. Of those analyzed, she named 42% of the individuals. Personal Genome Project later confirmed 97% of her submitted names according to Forbes.
In testimony before the Privacy and Integrity Advisory Committee of the Department of Homeland Security (DHS), Latanya Sweeney, PhD (above), Professor and Director at Harvard’s Data Privacy Lab stated, “One problem is that people don’t understand what makes data unique or identifiable. For example, in 1997 I was able to show how medical information that had all explicit identifiers, such as name, address and Social Security number removed could be reidentified using publicly available population registers (e.g., a voter list). In this particular example, I was able to show how the medical record of William Weld, the Governor of Massachusetts of the time, could be reidentified using only his date of birth, gender, and ZIP. In fact, 87% of the population of the United States is uniquely identified by date of birth (e.g., month, day, and year), gender, and their 5-digit ZIP codes. The point is that data that may look anonymous is not necessarily anonymous. Scientific assessment is needed.” (Photo copyright: US Department of Health and Human Services.)
“Open publication of deidentified records like health, census, tax or Centrelink data is bound to fail, as it is trying to achieve two inconsistent aims: the protection of individual privacy and publication of detailed individual records,” Dr. Teague noted in the UM news release. “We need a much more controlled release in a secure research environment, as well as the ability to provide patients greater control and visibility over their data.”
While studies are mounting to show how vulnerable deidentified information might be, there’s little in the way of movement to fix the issue. Nevertheless, clinical laboratories should consider carefully any decision to sell anonymized (AKA, blinded) patient data for data mining purposes. The data may still contain enough identifying information to be used inappropriately. (See Dark Daily, “Coverage of Alexion Investigation Highlights the Risk to Clinical Laboratories That Sell Blinded Medical Data,” June 21, 2017.)
Should regulators and governments address the issue, clinical laboratories and healthcare providers could find more stringent regulations on the sharing of data—both identified and deidentified—and increased liability and responsibility regarding its governance and safekeeping.
Until then, any healthcare professional or researcher should consider the implications of deidentification—both to patients and businesses—should people use the data shared in unexpected and potentially malicious ways.
