"Speeding Up the Diagnosis Process," by Zhandong Liu

Scientist Zhandong Liu uses AI to speed up the diagnosis process.

Transcript

My name is Zhandong Liu. I'm an associate professor at the Baylor College of Medicine and also the chief data scientist at the Texas Children's Hospital. I was involved in a CZI project with Hugo Bellen and Shinya Yamamoto on how to speed and accelerate the diagnosis process.

My lab focused on developing AI algorithms. I was brought in this project to kind of figure out how to use AI to speed up the process.

Our algorithms takes the genome sequencing files from a patient along with their clinical files and process it using a tool called AI‑MARRVEL and will generate a small list of candidate variants and genes that can explain the phenotypes of the patient.

These algorithms were trained on a large amount of data that's been curated through Baylor Genetics, Baylor College of Medicine, The Undiagnosed Diseases Network. As you all know, that data is AI nowadays, right? When you are talking about high quality AI algorithms, oftentimes, those were trained on very good data sets.

We happen to have access to some of the top quality data sets that's curated at Baylor College of Medicine. These are about 4.5 million variants that have been reviewed by our board‑certified clinical geneticist. And based on those data sets along with the expert knowledge that we learned by interviewing those domain experts, we were able to create this state‑of‑the‑art artificial intelligent algorithm called AI‑MARRVEL.

We have used this algorithms on a couple projects. The first one is The Undiagnosed Diseases Network project where we were doing reanalysis. The second one is a project sponsored by CZI. It's called TMC‑CZI. A lot of the children that go through Texas Children's Hospital were sequenced and our algorithms was used to help them to do primary diagnosis and then secondary analysis as well.

The third project is the one that's sponsored by NIH called the Texome Project by Hugo Bellen and the Michael Wangler, where we were helping underserved population to gain access to whole exome sequencing, whole genome sequencing platforms and enable the AI diagnosis on this small population.

So, overall, the tool has been developed for almost two years and we have seen this tool being used in many groups and enabled to identify those very difficult variants used from hundreds or thousands of mutations.

"The Gift," by Gareth Baynam

Three Aboriginal children hold the key for unlocking important medical insights.

Transcript

I'd love to share with you a story, a story about a gift, a gift that keeps on giving, a gift from one of the most remote places in the world, in the western desert of Western Australia, a gift, a gift from three remarkable Aboriginal children, who each in turn were born with a devastating condition, a condition affecting their hearts, their brains, their breathing, their learning. They then ultimately went on to develop intellectual disability and seizures. A gift that transverses time and transverses our planet.

These three children unlocked incredible medical insights. They were discovered to have a rare condition, a glitch into a change in a single chemical in a single gene, a gene called MTOR. This change made the gene work way too much. It was overactive and that caused chaos throughout their bodies.

When we first found this gene change, there was no map. There was no map to compare this gene change against for Aboriginal people, to know whether or not this was an abnormal gene change.

So then we had to go on a remarkable journey. We searched all over the world to find people that could prove whether or not this gene change was in fact the cause of these children's condition.

After circling the world, we kind of landed in our backyard. We landed on our own country with an immunology lab. They proved that that gene in fact did work far too much in experiments in cells in the laboratory. But much more importantly, they also showed that if we gave a commonly used medicine, a cheap medicine with a known side effect profile, that we could reverse the effect of that faulty gene in those cells.

Suddenly, we not only knew definitively what the cause of this children's condition was but we immediately had an option for their treatment using an existing drug, something we could take off the shelf. We didn't need to go through a billion dollars and 20 years of drug development. We could use that right now.

This condition ultimately came to be known as Smith‑Kingsmore Syndrome.

With the permission of the family, we published this information to see if there are other families around the world. And then a chain reaction of events occurred as others were diagnosed around the world, a bit like cousins around the world for these Aboriginal children.

Then there were new insights. In Germany, two siblings were identified with the condition, teenagers. And they had bowel polyps. That's very unusual in teenagers. Bowel polyps are the precursor of bowel cancer.

So, suddenly, we didn't potentially only have a treatment for seizures, intellectual disability, but also potentially bowel cancer. Again, something that was off the shelf.

Not only does this gift give internationally, it gave locally to our community in Western Australia. We solved this medical mystery using genomic sequencing back in 2013. It was the first time we had used that as a clinical test. That then gave our health system and it gave the Aboriginal communities the trust and the confidence to be able to do that more. It set up our Rare and Undiagnosed Diseases Diagnostic Service and, ultimately, what became the Undiagnosed Diseases Program.

The gift keeps on giving, because that Aboriginal family taught us how to provide the best medical care, how to embrace Aboriginal ways of knowing, being and belonging to help everybody.

We then took those principles to design how we provided care coordination for people with rare and undiagnosed diseases, care coordination across all of what it means to live a life in children, be it health, education, disability and social services.

So, to that Aboriginal family, to those three children, those incredible, vulnerable, special, powerful children from one of the remotest corners of the earth.

Thank you.