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.

Having become a mother at 18, this is supposed to be the year Katie Stevens figures out who she is — but then she discovers her 12-year-old son is terribly ill.

TRANSCRIPT

12 years ago, my day‑to‑day worries included things like, did the kids make it to school on time? For the first time ever, all three of my kids were in school. Did the laundry get done? Did I get up at 5:00 AM for my six‑mile run?

I remember telling my friend this was going to be the year that I get some rest and I figure out who I am. I'd been a mother since I was 18 years old and I was excited to think about going back to school.

My oldest, Riley, was born a perfectly healthy little boy. He grew into a very strong 11‑year‑old who is running 5Ks alongside me. That summer, we started to notice some abnormal bruising. Things like seatbelts would leave marks across his neck. His friends who played soccer, their legs looked fine, but Riley's were littered with bruises.

We took Riley to his annual visit in August and his pediatrician assured me that it was okay to wait for lab tests and that we didn't have a history of cancer in our family, so it was okay. Things were going to be okay. He scheduled labs to be drawn in October.

Over the next few weeks, we started to notice little things, like a cough that just wouldn't go away or, when he went for a run with his Dad, he said he just felt really tired. My gut was telling me there was something to be worried about, but I brushed it aside because his doctor said it was okay. What did I know? I was just a mom.

The night before his blood draw, we watched a St. Jude's commercial. I looked at my husband and I said, “I think something's really wrong with Riley.”

We pulled up to the lab and I prepped Riley. It was just going to be one poke. I would hold his hand and we’d go get one of those $1.50 hotdogs from Costco.

They drew 14 vials of blood. We got home that afternoon and Riley went outside with the kids to play. And he ran in and asked something. His face was sweaty, his hair was sweaty but he was smiling, but he was blue.

I put my ear to his chest to make sure he was breathing okay, because I thought for sure that was it. Little did I know, those 14 vials of blood had drained him of the already dwindling blood supply.

I called his doctor. He told me to get Riley to the ER. I didn't know then that he had already seen the results of Riley's blood draw.

The ER drew labs again. They looked at me and said, “You need to get him in the car. You need to get him over to the next state,” which was Washington, into the children's hospital because my rural Idaho hospital couldn't handle what was happening to him.

The doctor at the children's hospital pulled my husband and I into a tiny room away from Riley and told us the devastating news that our child who had been hiking mountains over the summer either was in bone marrow failure or had cancer. His body was no longer equipped to sustain life.

Less than 12 hours since we were eating a hotdog at Costco, we were admitted to the hematology‑oncology floor.

As we got settled in for the night, I was tucking him into his hospital bed. How had I not noticed how pale he had become? His white skin matched the sheets and the hospital lighting and all I could see were his blue eyes that were full of fear.

“Please sleep with me in bed tonight, Mama. I'm really scared.”

My only worry now was that I needed to save my child's life.

The next morning, my husband came and I asked if I could step into the hallway. I covered my mouth and I sobbed and I shook and I broke. I couldn't let him see me like this. I couldn't make it so scary. How was I going to hide that I knew he could die?

Riley was diagnosed with severe aplastic anemia, a rare bone marrow failure disorder. The cause was unknown, but our family history, again, didn't make anyone think it could be genetic.

Riley had had two options at survival. Two. One was an immunosuppressive therapy that should train his body to quit attacking itself. The trick, he couldn't have an underlying genetic condition for it to work.

The second was a stem cell transplant. It was much more dangerous and his best chance at life would be if he had a sibling match. The problem, neither one of our children was a match for him.

So, because there was no known genetic issue, because testing hadn't been run, and he didn't have a sibling match, immunosuppressive therapy was ordered to start on Halloween.

Here's the thing. My deep knowing knew we were going to be headed to stem cell transplant if this didn't work. And my deep knowing knew that my thriving child didn't go from perfectly healthy to dying. That just doesn't happen.

My life was so different from where it was three weeks prior. I was still worried about laundry, but this time I was delegating it to whoever was able to help us at the time. I was coordinating hospital dinners with my family just to try to keep some sense of normalcy.

I was fighting insurance companies and I was fundraising just to make ends meet and to make sure my littles could stay in swim lessons.

16 weeks would have to go by before telomere length was performed and showed that Riley did have a genetic condition. Remember the immunosuppressive therapy? Well, it was a fucking nightmare to watch him go through and it was never going to work.

Telomeres. This was a word that had never crossed my lips. My 11‑year‑old knew it from middle school biology and I started realizing right then and there it was up to me to understand all the nuances of the science that was happening inside of him and the treatment available to him, because you know what? Doctors have a lot of patients, but I only had one Riley.

Telomeres were the word that changed my universe. They're the protective end cap of our DNA and they work like the aglet of a shoelace. They keep our DNA from unraveling. When we're born, ideally, they're longer. And as we age, they shorten. Riley’s are what you would expect in an 80 to 90‑year‑old person.

In the midst of all this, we're trying to find resources. One co‑pay was $800 a month. Our case manager was amazing and he tried to prepare me. He said, “You're going to be in this ocean of cancer and aplastic anemia is this little, tiny island.” And now we had the diagnosis of telomeres and we were on a rock, stranded. Alone.

This was the dance I found myself in for the rest of Riley's journey. Patients with short telomeres can't have a standard stem cell transplant protocol. Alkylating chemos and radiation destroy them, and the data showed there was very few that survived it.

They told us that Riley had a donor identified, a 23‑year‑old male who wasn't answering the phone. To me, the most logical thing to do was to tell them to call his mom.

In this time of sheer chaos, Riley's body was somehow giving us time to find the right path. We were connected to the patient advocacy group via Facebook and they were hosting a camp in Maine, where experts from around the world would be and other families like ours would be there as well. We went and we were welcomed with open arms. We were no longer alone.

We met a doctor who had designed a protocol, stem cell transplant, for patients with short telomeres. The clinical trial already had patients that had gone through it and it showed that they were doing very well.

Coming home, I was so excited to tell our hematologist what I had learned. Riley met all the criteria for this clinical trial. We knew it was a risk, but all transplants are a risk and I wanted to spare him the complications that I knew he would endure due to his genetic condition.

He looked at me and smiled. I think we're just going to stay with the plan.

Riley doesn't show the typical signs of someone with a telomere issue. This time, though, I wasn't going to listen just because they told me to. This time, my gut told me that this was the treatment that was right for Riley.

I moved Riley 3,000 miles from home. I left behind my other children and my husband. Riley was number six in the world to undergo this clinical trial. We Life Flighted the now 24‑year‑old’s marrow from Germany. He picked up the phone.

Riley's body accepted his cells as his own and, now, nine years later, we have never been back in a hospital in all that time.

A year later, we were back to status quo, but for me it was too quiet. To my surprise, I had found out about myself. Through this process, I learned that I really understood and enjoyed the complexities of genetics. Helping people that were on that rock felt like it was my calling. I was asked not to just help but to step into the role as the first executive director of the leading international research and advocacy patient organization for telomere biology disorders.

Today, I worry if someone has received proper diagnostic testing, if a clinical trial is developed in an equitable and accessible way. I worry about grants and fundraisers and sell lines. I worry if Riley and Olivia are doing okay in college. I worry if Ethan is enjoying his senior year. Oh, yeah, I had another baby during this. Grayson is 11 and he knows what telomeres are too.

Some things never change. I still need to do the laundry, I still need to run, and Costco hotdogs are still $1.50.

Thank you.