For over three decades, a highly accurate early diagnostic test for ovarian cancer has eluded physicians. Now, scientists in the Georgia Tech Integrated Cancer Research Center (ICRC) have combined machine learning with information on blood metabolites to develop a new test able to detect ovarian cancer with 93 percent accuracy among samples from the team’s study group.

John McDonald, professor emeritus in the School of Biological Sciences, founding director of the ICRC, and the study’s corresponding author, explains that the new test’s accuracy is better in detecting ovarian cancer than existing tests for women clinically classified as normal, with a particular improvement in detecting early-stage ovarian disease in that cohort.

The team’s results and methodologies are detailed in a new paper, “A Personalized Probabilistic Approach to Ovarian Cancer Diagnostics,” published in the March 2024 online issue of the medical journal Gynecologic Oncology. Based on their computer models, the researchers have developed what they believe will be a more clinically useful approach to ovarian cancer diagnosis — whereby a patient’s individual metabolic profile can be used to assign a more accurate probability of the presence or absence of the disease.

“This personalized, probabilistic approach to cancer diagnostics is more clinically informative and accurate than traditional binary (yes/no) tests,” McDonald says. “It represents a promising new direction in the early detection of ovarian cancer, and perhaps other cancers as well.”

The study co-authors also include Dongjo Ban, a Bioinformatics Ph.D. student in McDonald’s lab; Research Scientists Stephen N. Housley, Lilya V. Matyunina, and L.DeEtte (Walker) McDonald; Regents’ Professor Jeffrey Skolnick, who also serves as Mary and Maisie Gibson Chair in the School of Biological Sciences and Georgia Research Alliance Eminent Scholar in Computational Systems Biology; and two collaborating physicians: University of North Carolina Professor Victoria L. Bae-Jump and Ovarian Cancer Institute of Atlanta Founder and Chief Executive Officer Benedict B. Benigno. Members of the research team are forming a startup to transfer and commercialize the technology, and plan to seek requisite trials and FDA approval for the test.

Silent killer

Ovarian cancer is often referred to as the silent killer because the disease is typically asymptomatic when it first arises — and is usually not detected until later stages of development, when it is difficult to treat.

McDonald explains that while the average five-year survival rate for late-stage ovarian cancer patients, even after treatment, is around 31 percent — but that if ovarian cancer is detected and treated early, the average five-year survival rate is more than 90 percent.

“Clearly, there is a tremendous need for an accurate early diagnostic test for this insidious disease,” McDonald says.

And although development of an early detection test for ovarian cancer has been vigorously pursued for more than three decades, the development of early, accurate diagnostic tests has proven elusive. Because cancer begins on the molecular level, McDonald explains, there are multiple possible pathways capable of leading to even the same cancer type.

“Because of this high-level molecular heterogeneity among patients, the identification of a single universal diagnostic biomarker of ovarian cancer has not been possible,” McDonald says. “For this reason, we opted to use a branch of artificial intelligence — machine learning — to develop an alternative probabilistic approach to the challenge of ovarian cancer diagnostics.”

Metabolic profiles

Georgia Tech co-author Dongjo Ban, whose thesis research contributed to the study, explains that “because end-point changes on the metabolic level are known to be reflective of underlying changes operating collectively on multiple molecular levels, we chose metabolic profiles as the backbone of our analysis.”

“The set of human metabolites is a collective measure of the health of cells,” adds coauthor Jeffrey Skolnick, “and by not arbitrarily choosing any subset in advance, one lets the artificial intelligence figure out which are the key players for a given individual.”

Mass spectrometry can identify the presence of metabolites in the blood by detecting their mass and charge signatures. However, Ban says, the precise chemical makeup of a metabolite requires much more extensive characterization.

Ban explains that because the precise chemical composition of less than seven percent of the metabolites circulating in human blood have, thus far, been chemically characterized, it is currently impossible to accurately pinpoint the specific molecular processes contributing to an individual's metabolic profile.

However, the research team recognized that, even without knowing the precise chemical make-up of each individual metabolite, the mere presence of different metabolites in the blood of different individuals, as detected by mass spectrometry, can be incorporated as features in the building of accurate machine learning-based predictive models (similar to the use of individual facial features in the building of facial pattern recognition algorithms).

“Thousands of metabolites are known to be circulating in the human bloodstream, and they can be readily and accurately detected by mass spectrometry and combined with machine learning to establish an accurate ovarian cancer diagnostic,” Ban says.

A new probabilistic approach

The researchers developed their integrative approach by combining metabolomic profiles and machine learning-based classifiers to establish a diagnostic test with 93 percent accuracy when tested on 564 women from Georgia, North Carolina, Philadelphia and Western Canada. 431 of the study participants were active ovarian cancer patients, and while the remaining 133 women in the study did not have ovarian cancer.

Further studies have been initiated to study the possibility that the test is able to detect very early-stage disease in women displaying no clinical symptoms, McDonald says.

McDonald anticipates a clinical future where a person with a metabolic profile that falls within a score range that makes cancer highly unlikely would only require yearly monitoring. But someone with a metabolic score that lies in a range where a majority (say, 90%) have previously been diagnosed with ovarian cancer would likely be monitored more frequently — or perhaps immediately referred for advanced screening.

Citation: https://doi.org/10.1016/j.ygyno.2023.12.030

Funding

This research was funded by the Ovarian Cancer Institute (Atlanta), the Laura Crandall Brown Foundation, the Deborah Nash Endowment Fund, Northside Hospital (Atlanta), and the Mark Light Integrated Cancer Research Student Fellowship.

Disclosure

Study co-authors John McDonald, Stephen N. Housley, Jeffrey Skolnick, and Benedict B. Benigno are the co-founders of MyOncoDx, Inc., formed to support further research, technology transfer, and commercialization for the team’s new clinical tool for the diagnosis of ovarian cancer.

Whether you’ve always wanted to see a real brain, are curious about the science behind coffee brewing, or anything in between, there’s one event you should have marked on your calendar: the Atlanta Science Festival.

“The festival spans three weeks and includes events all over town,” says Jennifer Leavey, assistant dean for Faculty Mentoring in the College of Sciences, principal academic professional in the School of Biological Sciences, longtime festival volunteer. “It helps me recharge my science enthusiasm batteries every year and lets me approach science education creatively.”

The annual festival features over 150 science-themed events for all ages and has become an Atlanta staple over the past decade. This year, the festival will host events from March 9 to March 22, culminating in the Exploration Expo event in Piedmont Park featuring 100 different demonstrations — on March 23. 

As one of its founding partners, Georgia Tech has served a key role in the Festival for over a decade. Last year’s iteration featured several events hosted by Tech — from a science fashion show to a virtual college prep workshop — hosted by volunteers from across campus.

“As a volunteer, you could help with one of the partner events or the Exploration Expo: the culminating street party at the end of the festival,” says Leavey. “Volunteering is a great way to meet people, learn more about science, get in events for free, and share your love of science with the community.”

Here are a few ways to get involved with this year’s festival. Look out for the full schedule and attendee registration on the Atlanta Science Festival website. 

Volunteer for GT Science and Engineering Day | March 9

For several years, Georgia Tech has opened its doors to the Atlanta community during Science and Engineering Day. With demonstrations on everything from robotics and neuroscience to paper and chemical engineering, there’s always been an activity for everyone. Last year’s event saw over 1,500 attendees, with more than 40 host units and student organizations.

This year, Science and Engineering Day will serve as the kickoff event for the entire festival, taking place on March 9 from 10 A.M. to 2 P.M. Those interested in volunteering or hosting a demonstration of their work should register here by January 25.

Visit research.gatech.edu/ATLScienceFestival to learn more.

High School Math Day | March 9

Science and Engineering Day will also host this year’s High School Math Day, a tradition at Georgia Tech since 1958. A day of logic puzzles, math demonstrations, and friendly competition, last year’s event saw over 250 students, parents, and teachers from 42 schools around the state.

“My favorite part of High School math day is seeing all the students get excited about doing the activities with each other and winning the awards at the end of the day,” says Lea Marzo, program operations director for the College’s Center for Promoting Inclusion and Equity in the Sciences (C-PIES) and one of the co-organizers of the event.

If you know a high schooler who is a math expert or even math-curious, encourage them to stop by on March 9 from 10 A.M. to 2 P.M.

“It really is for any level of Math — whether you are in 9th grade Math or more advanced Math,” says Marzo. “There are a lot of activities planned for students and it includes food and a cool T-Shirt!”

Visit hsmd.math.gatech.edu to learn more.

Host a demonstration at the Exploration Expo | March 23

The Exploration Expo is the finale to the Festival, taking over Piedmont park every year with roughly 100 different science demonstrations. Often referred to as “Atlanta’s biggest science party,” this free event has a little something for everyone.

“Whether you’re about to start preschool or volunteering with your grandkids, you’re here because you also believe that Atlanta is a science city — that we’re here to learn, teach one another, and improve our world through shared inquiry,” shares Jess Hunt-Ralston, director of Communications for the College of Sciences at Georgia Tech, who also represents the Institute on the Science ATL Board of Directors. “And there’s nothing quite like seeing the scales of a butterfly wing for the first time, playing brain games with new friends, or peering through a telescope together to help spark and sustain that spirit of curiosity.”

Contact Jennifer Leavey (jennifer.leavey@cos.gatech.edu) for more information.

Volunteer for other events at the Festival

Interested in volunteering at the Festival in another way? Learn more about how to volunteer here.

After the Festival: Georgia Tech Energy Materials Day | March 27

If you're looking for more science after the festival, join us for the Georgia Tech Energy Materials Day on March 27 at the Georgia Tech Exhibition Hall. This event will bring together representatives from academia, government, and industry to accelerate energy materials research. It will also provide an opportunity for key stakeholders to interact with Georgia Tech researchers in this important area.

Register for the event here, or click here to learn more.

Ascend, a new career development program for mid-career faculty, launched its cohort for Spring 2024. Supported by the Office of Faculty Professional Development, Ascend cohort members include academic professionals and lecturers from across campus.  

The cohort will build on current strengths and successes and explore ways to thrive mid-career and in the future. Using a faculty learning community model and the Appreciative Inquiry framework, participants will explore their interests, values, and goals, and create an actionable, individual strategic plan while developing skills for career growth and leadership. 

Members of the first cohort include: 

• Whitney Buser - Director of Master’s Programs and Associate Director of Academic Programs, School of Economics 

• Melissa Foulger - Artistic Director for DramaTech, School of Literature, Media, and Communication 

• Laura Sams Haynes - Director of Outreach, School of Electrical and Computer Engineering 

• Mary Holder - Director of Neuroscience Program, Undergraduate Studies, School of Psychology 

• Christopher Jankowski - Director of Graduate Advising and Assessment, Director of Postdoctoral Teaching Effectiveness, School of Mathematics 

• Ashley McKeen - EXCEL Senior Lecturer, CEISMC

• Nicoly Myles - Director of the Center for Academics, Success, & Equity (CASE), School of Industrial and Systems Engineering 

• Amanda Nolen - Faculty Teaching and Learning Specialist, Center for Teaching and Learning 

• Matt Nusnbaum - Senior Academic Professional, Undergraduate Program in Neuroscience 

• Daniela Staiculescu - Senior Academic Professional, School of Electrical and Computer Engineering 

• Cassie Thomas - Associate Director of Undergraduate Transition Seminars, Office of Undergraduate Education 

• Ruthie Yow - Associate Director, Center for Sustainable Communities Research and Development. 

Participants in this program will learn to use the Appreciative Inquiry model to develop a personal development plan that includes a vision and mission; goals for personal learning, professional development, and career momentum; and an action plan. The program is designed to support faculty as they practice skills essential for collegiality and leadership in a cohort environment and explore opportunities for growth and career vitality at Georgia Tech. Participants will also take advantage of four professional coaching sessions during the calendar year with International Coaching Federation-accredited Director of the Office of Faculty Professional Development Rebecca Pope-Ruark.

Learn more about the Ascend program. 

You may be familiar with yeast as the organism content to turn carbs into products like bread and beer when left to ferment in the dark. In these cases, exposure to light can hinder or even spoil the process. 

In a new study published in Current Biology, researchers in Georgia Tech’s School of Biological Sciences have engineered one of the world’s first strains of yeast that may be happier with the lights on.

“We were frankly shocked by how simple it was to turn the yeast into phototrophs (organisms that can harness and use energy from light),” says Anthony Burnetti, a research scientist working in Associate Professor William Ratcliff’s laboratory and corresponding author of the study. “All we needed to do was move a single gene, and they grew 2% faster in the light than in the dark. Without any fine-tuning or careful coaxing, it just worked.”

Easily equipping the yeast with such an evolutionarily important trait could mean big things for our understanding of how this trait originated — and how it can be used to study things like biofuel production, evolution, and cellular aging.

Looking for an energy boost

The research was inspired by the group’s past work investigating the evolution of multicellular life. The group published their first report on their Multicellularity Long-Term Evolution Experiment (MuLTEE) in Nature last year, uncovering how their single-celled model organism, “snowflake yeast,” was able to evolve multicellularity over 3,000 generations.

Throughout these evolution experiments, one major limitation for multicellular evolution appeared: energy.

“Oxygen has a hard time diffusing deep into tissues, and you get tissues without the ability to get energy as a result,” says Burnetti. “I was looking for ways to get around this oxygen-based energy limitation.”

One way to give organisms an energy boost without using oxygen is through light. But the ability to turn light into usable energy can be complicated from an evolutionary standpoint. For example, the molecular machinery that allows plants to use light for energy involves a host of genes and proteins that are hard to synthesize and transfer to other organisms — both in the lab and naturally through evolution. 

Luckily, plants are not the only organisms that can convert light to energy.

Keeping it simple

A simpler way for organisms to use light is with rhodopsins: proteins that can convert light into energy without additional cellular machinery.

“Rhodopsins are found all over the tree of life and apparently are acquired by organisms obtaining genes from each other over evolutionary time,” says Autumn Peterson, a biology Ph.D. student working with Ratcliff and lead author of the study.

This type of genetic exchange is called horizontal gene transfer and involves sharing genetic information between organisms that aren’t closely related. Horizontal gene transfer can cause seemingly big evolutionary jumps in a short time, like how bacteria are quickly able to develop resistance to certain antibiotics. This can happen with all kinds of genetic information and is particularly common with rhodopsin proteins.

“In the process of figuring out a way to get rhodopsins into multi-celled yeast,” explains Burnetti, “we found we could learn about horizontal transfer of rhodopsins that has occurred across evolution in the past by transferring it into regular, single-celled yeast where it has never been before.”

To see if they could outfit a single-celled organism with solar-powered rhodopsin, researchers added a rhodopsin gene synthesized from a parasitic fungus to common baker’s yeast. This specific gene is coded for a form of rhodopsin that would be inserted into the cell’s vacuole, a part of the cell that, like mitochondria, can turn chemical gradients made by proteins like rhodopsin into energy. 

Equipped with vacuolar rhodopsin, the yeast grew roughly 2% faster when lit — a huge benefit in terms of evolution.

“Here we have a single gene, and we're just yanking it across contexts into a lineage that's never been a phototroph before, and it just works,” says Burnetti. “This says that it really is that easy for this kind of a system, at least sometimes, to do its job in a new organism.”

This simplicity provides key evolutionary insights and says a lot about “the ease with which rhodopsins have been able to spread across so many lineages and why that may be so,” explains Peterson, who Peterson recently received a Howard Hughes Medical Institute (HHMI) Gilliam Fellowship for her work. Carina Baskett, grant writer for Georgia Tech’s Center for Microbial Dynamics and Infection, also worked on the study.

Because vacuolar function may contribute to cellular aging, the group has also initiated collaborations to study how rhodopsins may be able to reduce aging effects in the yeast. Other researchers are already starting to use similar new, solar-powered yeast to study advancing bioproduction, which could mark big improvements for things like synthesizing biofuels.

Ratcliff and his group, however, are mostly keen to explore how this added benefit could impact the single-celled yeast’s journey to a multicellular organism. 

“We have this beautiful model system of simple multicellularity,” says Burnetti, referring to the long-running Multicellularity Long-Term Evolution Experiment (MuLTEE). “We want to give it phototrophy and see how it changes its evolution.”

Citation: Peterson et al., 2024, Current Biology 34, 1–7.

DOI: https://doi.org/10.1016/j.cub.2023.12.044 

The end of the year is often a time to look back and reflect on what has happened over the past 365 days. For Georgia Tech, it’s no different.

Here are some of the highlights and most widely read stories from the past year at the Institute — including a campus visit from Vice President Kamala Harris to discuss the climate crisis with College of Sciences faculty, record Institute enrollments and rankings, significant research advances, and $4.5 billion in contributions to the state economy.

Lizzie Wright was in 10th grade when she watched a TED Talk about controlling someone else’s arm with your brain.

“It got me thinking — we’re all walking around, talking to people, moving our hands, and just kind of taking it for granted,” she said. “We all have this brain and it looks pretty much the same on the outside, and has the same functions, yet we are all different. And we don’t fully know why. I wanted to know why.”

That curiosity led Wright to Georgia Tech, where she graduates this week with a bachelor’s degree in neuroscience, with minors in health and medical science and philosophy. She leaves behind a community that has become a defining part of her life.

Through EXCEL, Georgia Tech’s postsecondary education program for students with intellectual and developmental disabilities, Wright mentored five students and later served in a leadership role overseeing the entire group of mentors.

“EXCEL taught me more than anything else,” she said. “I learned skills like how to budget because we worked on that together, how to manage my time, how to walk into new environments and approach joining new clubs and groups.”

Wright was also selected for Ramblin’ Royalty in 2022, an honor bestowed on two students each year. Ramblin’ Royalty students serve throughout the year at campus events and in other leadership roles.

“I was nominated by my sorority, which was very humbling. I always thought about the idea of applying based on previous winners and what I’ve seen them do over the years, but I didn’t want to get my hopes up. Going through the process made me realize how much I love Georgia Tech and how grateful I am for this place, and it gave me a tangible way to give back.”

Through Greek life, Campus Outreach, and the EXCEL program, Wright not only found a path for her career but a path for her life.

“I joined all three my first year and just never really needed to find anything else. They all taught me that the Tech bubble, though it’s beautiful, there’s so much more outside of Tech, and that perspective kept me going. We’re all here for a reason, and that reason is to take what we’ve learned and go forth into the world.”

For Wright, that means completing her EMT certification with Grady Hospital and applying to medical school. Her passion for global health and medicine was solidified during a summer in Ethiopia working on a medical mission.

“It was my first full encounter with medicine. We were doing rounds one day, and the doctor I was working with came across this patient who had just had spinal surgery, but he had bedsores and needed to be lifted off the bed without having his spine compromised. Eventually, the doctor says, ‘My kid has a bike. Let’s take the tire off the bike, put it under his spine, and raise it so his skin can breathe.’ So he goes home, disassembles the bike, sterilizes the tire, and configures it in a way that raises the person up from the bed. And it worked. And it was just because his kid had a bike.

“That type of thinking — engineering thinking, even though I’m a neuroscience major — is so cool because you just work with what you’ve got.”

That unpredictability, and pursuing a career that could take her anywhere, is part of what drew Wright to medicine.

“That’s the reason I want to do EMT. You have no idea what you’re walking into. You have your jump bag, your partner, and your knowledge. What are you going to do? How are you going to help this person before you can get them to the hospital?”

As Wright prepares for Commencement, she’ll be joined by her family — including her brother Bishop, also a Tech graduate, who encouraged her to be a Yellow Jacket in the first place.

“He really pushed me early on to realize this wasn’t just a good school, but way more than that. Georgia Tech offers so much, but I would really advise most students to not just use it as a launchpad, but to acknowledge this place for the community it offers. I think that is key not only to enjoying the college experience, but really to seeing Georgia Tech for everything it has to offer and not waste these years.”