DNA screen: World-first preventative saliva test for cancer and heart disease risk

Young Australians can now access a free DNA saliva test to learn whether they face increased risk of some cancers and heart disease, which can be prevented or treated early if detected, in a world-first DNA screening study.

The nationally collaborative project, led by Monash University and supported by researchers and clinicians across Australia, will screen at least 10,000 people aged 18-40 for genes that increase risk of certain types of cancers and heart disease that often go undetected.

Those found to be at high risk after DNA testing – about one in 75 or 1.3 per cent – will have their situation explained by experts and be offered genetic counselling and prevention measures, such as regular scans and check-ups.

cancer

cancer/photo:en.wikipedia.org

Until now, genetic testing for the DNA changes that increase disease risk has only been available on a small scale for those with a known family history or prior disease diagnosis. Population testing, open to everyone, has the potential to drastically improve access and maximize the preventive benefits of DNA testing.

Monash University’s Associate Professor Paul Lacaze said the project enabled a more efficient and equitable approach to genetic testing, identifying far more people at high risk than current testing methods.

“We hope to identify those at risk while they are young and healthy, not after the fact, and empower them to make more informed decisions about their health,” he said. “For some people, this could save their lives through early detection and prevention of cancer and heart disease. This will also save considerable health system costs in Australia through prevention.

“Providing genetic testing based on family history alone is not enough. Up to 90 per cent of those at high risk in the general population are not identified by current family history-based testing. Most people don’t find out about their genetic risk until it’s too late, like after an incurable cancer or heart attack is diagnosed. We want to change that.”

DNA Screen will identify people with DNA variants in the BRCA1 and BRCA2 genes that lead to an increased risk of hereditary breast and ovarian cancer in women. These genes are also linked to breast and prostate cancer in men, although not as strongly. Men and women who carry DNA variants in the BRCA1 and BRCA2 genes can also pass them onto their children.

The DNA Screen test will also focus on Lynch Syndrome – another condition that increases risk for colorectal, endometrial, and other gastrointestinal cancers. Both cancer-related conditions have effective, proven interventions available to reduce risk if identified early.

This includes attending annual check-ups and screens from age 30, and the option of risk-reducing surgery for some people. Early detection and prevention are often life-saving for cancer.

The DNA test also encompasses heart disease risk, focusing on familial hypercholesterolemia (FH) or ‘genetic high cholesterol’, which results in high risk of heart disease from a young age. Despite effective medications such as statins being available to reduce risk, an estimated 95 per cent of FH carriers are currently undiagnosed.

Associate Professor Lacaze, from the Monash University School of Public Health and Preventive Medicine, is leading a team of national collaborators who were awarded a $2.97 million Medical Research Future Fund (MRFF) grant for the project. The project is supported by the Precision Medicine laboratory at Monash University and the state-of-the-art Biobanking Victoria facility.

The eventual goal is to develop a new population-based DNA screening program that could be offered through the Australian public healthcare system, available to everyone but targeted on certain medically-actionable conditions where early detection is key.

“We expect to identify about 1 in 75 people at high risk of these diseases. Those found to be high risk won’t necessarily get the disease, but pinpointing risk before symptoms appear enables prevention through regular check-ups, medication, or risk-reducing surgery. It could save their life.

DNA Screen, which is recruiting young people via social media, is expected to save lives and could lead to a wide scale preventive DNA testing program for cancer and heart disease risk, where early detection and prevention can be life-saving.

DNA Screen is the world’s first preventive DNA screening study designed specifically to assess population DNA screening through a national healthcare system. The test is free and involves placing a saliva sample into a small tube received by mail, and sending it back in a postage paid envelope. People can sign up online at dnascreen.monash.edu

 

Using machine learning to improve patient care

Doctors are often deluged by signals from charts, test results, and other metrics to keep track of. It can be difficult to integrate and monitor all of these data for multiple patients while making real-time treatment decisions, especially when data is documented inconsistently across hospitals.

In a new pair of papers, researchers from MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) explore ways for computers to help doctors make better medical decisions.

One team created a machine-learning approach called “ICU Intervene” that takes large amounts of intensive-care-unit (ICU) data, from vitals and labs to notes and demographics, to determine what kinds of treatments are needed for different symptoms. The system uses “deep learning” to make real-time predictions, learning from past ICU cases to make suggestions for critical care, while also explaining the reasoning behind these decisions.

“The system could potentially be an aid for doctors in the ICU, which is a high-stress, high-demand environment,” says PhD student Harini Suresh, lead author on the paper about ICU Intervene. “The goal is to leverage data from medical records to improve health care and predict actionable interventions.”

Another team developed an approach called “EHR Model Transfer” that can facilitate the application of predictive models on an electronic health record (EHR) system, despite being trained on data from a different EHR system. Specifically, using this approach the team showed that predictive models for mortality and prolonged length of stay can be trained on one EHR system and used to make predictions in another.

ICU Intervene was co-developed by Suresh, undergraduate student Nathan Hunt, postdoc Alistair Johnson, researcher Leo Anthony Celi, MIT Professor Peter Szolovits, and PhD student Marzyeh Ghassemi. It was presented this month at the Machine Learning for Healthcare Conference in Boston.

EHR Model Transfer was co-developed by lead authors Jen Gong and Tristan Naumann, both PhD students at CSAIL, as well as Szolovits and John Guttag, who is the Dugald C. Jackson Professor in Electrical Engineering. It was presented at the ACM’s Special Interest Group on Knowledge Discovery and Data Mining in Halifax, Canada.

Both models were trained using data from the critical care database MIMIC, which includes de-identified data from roughly 40,000 critical care patients and was developed by the MIT Lab for Computational Physiology.

ICU Intervene

Integrated ICU data is vital to automating the process of predicting patients’ health outcomes.

“Much of the previous work in clinical decision-making has focused on outcomes such as mortality (likelihood of death), while this work predicts actionable treatments,” Suresh says. “In addition, the system is able to use a single model to predict many outcomes.”

ICU Intervene focuses on hourly prediction of five different interventions that cover a wide variety of critical care needs, such as breathing assistance, improving cardiovascular function, lowering blood pressure, and fluid therapy.

At each hour, the system extracts values from the data that represent vital signs, as well as clinical notes and other data points. All of the data are represented with values that indicate how far off a patient is from the average (to then evaluate further treatment).

Importantly, ICU Intervene can make predictions far into the future. For example, the model can predict whether a patient will need a ventilator six hours later rather than just 30 minutes or an hour later. The team also focused on providing reasoning for the model’s predictions, giving physicians more insight.

“Deep neural-network-based predictive models in medicine are often criticized for their black-box nature,” says Nigam Shah, an associate professor of medicine at Stanford University who was not involved in the paper. “However, these authors predict the start and end of medical interventions with high accuracy, and are able to demonstrate interpretability for the predictions they make.”

The team found that the system outperformed previous work in predicting interventions, and was especially good at predicting the need for vasopressors, a medication that tightens blood vessels and raises blood pressure.

In the future, the researchers will be trying to improve ICU Intervene to be able to give more individualized care and provide more advanced reasoning for decisions, such as why one patient might be able to taper off steroids, or why another might need a procedure like an endoscopy.

EHR Model Transfer

Another important consideration for leveraging ICU data is how it’s stored and what happens when that storage method gets changed. Existing machine-learning models need data to be encoded in a consistent way, so the fact that hospitals often change their EHR systems can create major problems for data analysis and prediction.

That’s where EHR Model Transfer comes in. The approach works across different versions of EHR platforms, using natural language processing to identify clinical concepts that are encoded differently across systems and then mapping them to a common set of clinical concepts (such as “blood pressure” and “heart rate”).

For example, a patient in one EHR platform could be switching hospitals and would need their data transferred to a different type of platform. EHR Model Transfer aims to ensure that the model could still predict aspects of that patient’s ICU visit, such as their likelihood of a prolonged stay or even of dying in the unit.

“Machine-learning models in health care often suffer from low external validity, and poor portability across sites,” says Shah. “The authors devise a nifty strategy for using prior knowledge in medical ontologies to derive a shared representation across two sites that allows models trained at one site to perform well at another site. I am excited to see such creative use of codified medical knowledge in improving portability of predictive models.”

With EHR Model Transfer, the team tested their model’s ability to predict two outcomes: mortality and the need for a prolonged stay. They trained it on one EHR platform and then tested its predictions on a different platform. EHR Model Transfer was found to outperform baseline approaches and demonstrated better transfer of predictive models across EHR versions compared to using EHR-specific events alone.

In the future, the EHR Model Transfer team plans to evaluate the system on data and EHR systems from other hospitals and care settings.

Both papers were supported, in part, by the Intel Science and Technology Center for Big Data and the National Library of Medicine. The paper detailing EHR Model Transfer was additionally supported by the National Science Foundation and Quanta Computer, Inc.

Noninvasive eye scan could detect key signs of Alzheimer’s years before patients show symptoms

Cedars-Sinai neuroscience investigators have found that Alzheimer’s disease affects the retina — the back of the eye — similarly to the way it affects the brain. The study also revealed that an investigational, noninvasive eye scan could detect the key signs of Alzheimer’s disease years before patients experience symptoms.

Using a high-definition eye scan developed especially for the study, researchers detected the crucial warning signs of Alzheimer’s disease: amyloid-beta deposits, a buildup of toxic proteins. The findings represent a major advancement toward identifying people at high risk for the debilitating condition years sooner.

The study, published today in JCI Insight, comes amid a sharp rise in the number of people affected by the disease. Today, more than 5 million Americans have Alzheimer’s disease. That number is expected to triple by 2050, according to the Alzheimer’s Association.

“The findings suggest that the retina may serve as a reliable source for Alzheimer’s disease diagnosis,” said the study’s senior lead author, Maya Koronyo-Hamaoui, PhD, a principal investigator and associate professor in the departments of Neurosurgery and Biomedical Sciences at Cedars-Sinai. “One of the major advantages of analyzing the retina is the repeatability, which allows us to monitor patients and potentially the progression of their disease.”

Yosef Koronyo, MSc, a research associate in the Department of Neurosurgery and first author on the study, said another key finding from the new study was the discovery of amyloid plaques in previously overlooked peripheral regions of the retina. He noted that the plaque amount in the retina correlated with plaque amount in specific areas of the brain.

“Now we know exactly where to look to find the signs of Alzheimer’s disease as early as possible,” said Koronyo.

Keith L. Black, MD, chair of Cedars-Sinai’s Department of Neurosurgery and director of the Maxine Dunitz Neurosurgical Institute, who co-led the study, said the findings offer hope for early detection when intervention could be most effective.

“Our hope is that eventually the investigational eye scan will be used as a screening device to detect the disease early enough to intervene and change the course of the disorder with medications and lifestyle changes,” said Black.

For decades, the only way to officially diagnose the debilitating condition was to survey and analyze a patient’s brain after the patient died. In recent years, physicians have relied on positron emission tomography (PET) scans of the brains of living people to provide evidence of the disease but the technology is expensive and invasive, requiring the patient to be injected with radioactive tracers.

In an effort to find a more cost-effective and less invasive technique, the Cedars-Sinai research team collaborated with investigators at NeuroVision Imaging, Commonwealth Scientific and Industrial Research Organisation, University of Southern California, and UCLA to translate their noninvasive eye screening approach to humans.

The published results are based on a clinical trial conducted on 16 Alzheimer’s disease patients who drank a solution that includes curcumin, a natural component of the spice turmeric. The curcumin causes amyloid plaque in the retina to “light up” and be detected by the scan. The patients were then compared to a group of younger, cognitively normal individuals.