Lessons from the data: Applying machine learning for clinical decision support

machine learning clinical decision support

Mauricio Santillana, PhD, faculty member in the Computational Health Informatics Program at Boston Children’s Hospital, had an idea as he witnessed the volume of continuous real-time data generated in the pediatric intensive care unit (PICU). He realized that tapping the data on patients’ ever-changing vital signs, with the help of machine-learning algorithms, could support clinical decision-making and predict (and help head off) up-coming health issues.

He started a dialogue with the hospital’s Innovation & Digital Health Accelerator, and now collaborates closely with clinicians in the PICU to create machine-learning algorithms that can help them provide the highest level of care.

“It’s fairly recent that clinicians realized people with backgrounds in math and statistics can be very helpful in a clinical context,” says Santillana

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Marching because science saves lives

Timelapse video: Boston’s March for Science in 120 seconds (Credit: Kat J. McAlpine)

One definition of science: “The field of study concerned with discovering and describing the world around us by observing and experimenting.”

Another, simpler definition: “The state of knowing.”

At Saturday’s March for Science in Boston, people brandished signs defending facts, data, even the act of thinking. But with the National Institutes of Health budget under attack — a potential 18 percent cut — the most compelling signs were those that stated: “Science saves lives.”

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Science then & now: Progress that you can see

Click and drag to compare and contrast archive photos from the lab with current-day images of research at Boston Children’s Hospital.

Then, 1986: Stuart H. Orkin, MD, examines the DNA sequence of a gene.

Now, 2017: Today, Orkin is associate chief of Hematology/Oncology and chairman of Pediatric Oncology at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center (DF/BC). In this photo, he examines a rendering of a gene regulatory molecule’s structure. Orkin’s lab investigates gene regulation of stem cell development, genetic vulnerabilities to cancer and gene and other therapies for treating hemoglobin disorders. 

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Angiogenesis: The slow growth of a science

angiogenesis

Sometimes a scientific idea takes a long time to make its way forward. Angiogenesis is a case in point. As surgeon-in-chief at Boston Children’s Hospital, Judah Folkman, MD, noted that malignant tumors often had a bloody appearance. In The New England Journal of Medicine in 1971, he hypothesized that tumors cannot grow beyond a certain size without a dedicated blood supply, and that “successful” tumors secrete an unknown substance that encourages blood vessel growth, or angiogenesis.

If angiogenesis could be blocked, he argued, tumors might not grow or spread. Rather than waging a toxic chemical and radiation battle with a tumor, one could starve it into submission by shutting down its blood supply.

The idea was roundly criticized.

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Culture shock: Why poliovirus had to live before it could die

Children with polio are treated in an iron lung
Pictured here in the 1950s, polio patients breathe with the help of an iron lung at Boston Children’s Hospital.

Today, stories of polio may seem like echoes from far-away history to those born after 1979, the year that polio was eradicated in the U.S. Since then, it has been customary for children to receive four doses of the polio vaccine to protect them from ever contracting the terrifying disease also known as “infantile paralysis.”

Polio, however, still afflicts people in some areas of the world today. It causes muscle wasting and — in the most severe cases — can completely rob a person of his or her ability to move or breathe, resulting in death.

In the U.S., research efforts to create a polio vaccine lasted much of the 20th century. Although the virus was thriving and spreading among people, researchers repeatedly failed at getting poliovirus to survive in culture.

Then, one of the most crucial breaks in the fight against polio occurred in a Boston Children’s Hospital laboratory in 1949, during the heyday of polio outbreaks.

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Can virtual reality headsets save vision in people with lazy eye?

Luminopia amblyopia virtual reality
IDHA’s Matt Murphy tries out Luminopia’s VR headset with Dean Travers (photo: Greb Weintraub)

Three to five percent of the population has amblyopia, a.k.a. lazy eye, in which a healthy eye never “learns” to see because isn’t used. This usually happens because of a focusing problem or subtle misalignment of that eye. The brain learns to ignore input from that eye, and unless this is noticed early, it weakens and can slowly go blind.

“When I can diagnose amblyopia early enough, I can treat it with an eye patch or eye drops to block the ‘good’ eye,” says David Hunter, MD, PhD, chief of ophthalmology at Boston Children’s Hospital. “This gives the eye with amblyopia time to catch up.”

Unfortunately, eye patching doesn’t work well at older ages, and kids hate the socially stigmatizing patches, which often need to be worn for more than a year. As Dean Travers, cofounder of Luminopia, put it at Boston Children’s Hospital’s Innovators’ Showcase last week, “Being a pirate isn’t cool for very long.”

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A 30-minute screening test for dyslexia?

dyslexia screening test
A dyslexia screening app in development could flag children at risk as early as age 4, when interventions are most effective.

Ten to 12 percent of school-aged children have dyslexia. It’s typically diagnosed in second or third grade, only after a child has struggled unsuccessfully at reading. As Nadine Gaab, PhD, of Boston Children’s Hospital puts it, diagnosis is primarily based upon a “wait-to-fail-approach.” And that comes along with considerable psychological damage and stigma.

“Late diagnosis of dyslexia very often leads to low self-esteem, depression and antisocial behavior,” she says. A much better time to look for early signs of dyslexia would be kindergarten or first grade. With early intervention, many children can attain an average reading ability.

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SPG47: When rare disease research gets a push from parents

SPG47 citizen science
Robbie’s parents are spurring scientific research into her ultra-rare neurodegenerative disorder.

Spastic Paraplegia 47 doesn’t roll off the tongue. The name is complicated and challenging, much like SPG47 itself. When I tell healthcare providers my 3-year-old daughter’s diagnosis, I take a deep breath and wait for the inevitable question: What, exactly, is that?

More than 70 types of Hereditary Spastic Paraplegia (HSP) have been identified to date; almost all are neurodegenerative. At best, HSP causes distress and disruption; at worst, it has devastating, potentially life-threatening consequences. Its “pure” form impairs the lower extremities, causing extreme spasticity and weakness. Its “complicated” form — like our daughter Robbie’s — also impacts systemic and/or neurologic function. Many HSP sub-types have been diagnosed in only a handful of people worldwide, leaving affected families feeling lost and disconnected.

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New dataset reveals the individuality of childhood cancers

Tumor cells, like the ones pictured here, have unique genetic profiles across childhood cancers
Imaging of tumor cells. A new dataset, one of the largest of its kind, contains the genomic profiles of 1,215 pediatric tumors.

Childhood cancers are rare and account for about one percent of U.S. cancer diagnoses. They differ from adult tumors in that they often arise from many more diverse kinds of cells, including embryonal tissues, sex-cord stromal cells of the ovary or testis, the brain’s neural and glial cells and more.

Yet although improved tumor detection and treatment have increased survival rates for many different cancer subtypes, more than 1,900 children across the U.S. still lose their battle each year.

A new dataset — comprising the genomic profiles of a huge array of pediatric tumors — could help change that.

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Science Seen: Tackling S. aureus by eavesdropping on infections

S. aureus vaccine messenger RNA transcriptome
This messenger RNA ‘heat map,’ generated from 50 patient samples, shows potential target proteins for a more effective S. aureus vaccine. The color scale indicates the magnitude of the transcription level, with red highest.

Staphylococcus aureus causes 11,000 deaths annually in the U.S. alone and is frequently antibiotic-resistant. It’s a leading cause of pneumonia, bloodstream infections, bone/joint infections and surgical site infections and the #1 cause of skin and soft tissue infections. Efforts to develop an S. aureus vaccine have so far failed: the vaccines don’t seem to be capturing the right ingredients to make people immune.

Kristin Moffitt, MD, in Boston Children’s Hospital’s Division of Infectious Diseases, took a step back and asked: “What proteins does S. aureus need to make to establish infection?” The answer, she reasoned, could point to new antigens to include in a vaccine.

The above image shows an early result from Moffitt’s investigation. It’s a “heat map” of the messenger RNA signature — a snapshot of the proteins S. aureus is potentially up-regulating during infection.

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