(Press-News.org) In a move that could reshape drug discovery, researchers at Harvard Medical School have designed an artificial intelligence model capable of identifying treatments that reverse disease states in cells.
Unlike traditional approaches that typically test one protein target or drug at a time in hopes of identifying an effective treatment, the new model, called PDGrapher and available for free, focuses on multiple drivers of disease and identifies the genes most likely to revert diseased cells back to healthy function.
The tool also identifies the best single or combined targets for treatments that correct the disease process. The work, described Sept. 9 in Nature Biomedical Engineering, was supported in part by federal funding.
By zeroing in on the targets most likely to reverse disease, the new approach could speed up drug discovery and design and unlock therapies for conditions that have long eluded traditional methods, the researchers noted.
“Traditional drug discovery resembles tasting hundreds of prepared dishes to find one that happens to taste perfect,” said study senior author Marinka Zitnik, associate professor of biomedical informatics in the Blavatnik Institute at HMS. “PDGrapher works like a master chef who understands what they want the dish to be and exactly how to combine ingredients to achieve the desired flavor.”
The traditional drug-discovery approach — which focuses on activating or inhibiting a single protein — has succeeded with treatments such as kinase inhibitors, drugs that block certain proteins used by cancer cells to grow and divide. However, Zitnik noted, this discovery paradigm can fall short when diseases are fueled by the interplay of multiple signaling pathways and genes. For example, many breakthrough drugs discovered in recent decades — think immune checkpoint inhibitors and CAR T-cell therapies — work by targeting disease processes in cells.
The approach enabled by PDGrapher, Zitnik said, looks at the bigger picture to find compounds that can actually reverse signs of disease in cells, even if scientists don’t yet know exactly which molecules those compounds may be acting on.
How PDGrapher works: Mapping complex linkages and effects
PDGrapher is a type of artificial intelligence tool called a graph neural network. This tool doesn’t just look at individual data points but at the connections that exist between these data points and the effects they have on one another.
In the context of biology and drug discovery, this approach is used to map the relationship between various genes, proteins, and signaling pathways inside cells and predict the best combination of therapies that would correct the underlying dysfunction of a cell to restore healthy cell behavior. Instead of exhaustively testing compounds from large drug databases, the new model focuses on drug combinations that are most likely to reverse disease.
PDGrapher points to parts of the cell that might be driving disease. Next, it simulates what happens if these cellular parts were turned off or dialed down. The AI model then offers an answer as to whether a diseased cell would happen if certain targets were “hit.”
“Instead of testing every possible recipe, PDGrapher asks: ‘Which mix of ingredients will turn this bland or overly salty dish into a perfectly balanced meal?’” Zitnik said.
Advantages of the new model
The researchers trained the tool on a dataset of diseased cells before and after treatment so that it could figure out which genes to target to shift cells from a diseased state to a healthy one.
Next, they tested it on 19 datasets spanning 11 types of cancer, using both genetic and drug-based experiments, asking the tool to predict various treatment options for cell samples it had not seen before and for cancer types it had not encountered.
The tool accurately predicted drug targets already known to work but that were deliberately excluded during training to ensure the model did not simply recall the right answers. It also identified additional candidates supported by emerging evidence. The model also highlighted KDR (VEGFR2) as a target for non-small cell lung cancer, aligning with clinical evidence. It also identified TOP2A — an enzyme already targeted by approved chemotherapies — as a treatment target in certain tumors, adding to evidence from recent preclinical studies that TOP2A inhibition may be used to curb the spread of metastases in non-small cell lung cancer.
The model showed superior accuracy and efficiency, compared with other similar tools. In previously unseen datasets, it ranked the correct therapeutic targets up to 35 percent higher than other models did and delivered results up to 25 times faster than comparable AI approaches.
What this AI advance spells for the future of medicine
The new approach could optimize the way new drugs are designed, the researchers said. This is because instead of trying to predict how every possible change would affect a cell and then looking for a useful drug, PDGrapher right away seeks which specific targets can reverse a disease trait. This makes it faster to test ideas and lets researchers focus on fewer promising targets.
This tool could be especially useful for complex diseases fueled by multiple pathways, such as cancer, in which tumors can outsmart drugs that hit just one target. Because PDGrapher identifies multiple targets involved in a disease, it could help circumvent this problem.
Additionally, the researchers said that after careful testing to validate the model, it could one day be used to analyze a patient’s cellular profile and help design individualized treatment combinations.
Finally, because PDGrapher identifies cause-effect biological drivers of disease, it could help researchers understand why certain drug combinations work — offering new biological insights that could propel biomedical discovery even further.
The team is currently using this model to tackle brain diseases such as Parkinson’s and Alzheimer’s, looking at how cells behave in disease and spotting genes that could help restore them to health. The researchers are also collaborating with colleagues at the Center for XDP at Massachusetts General Hospital to identify new drug targets and map which genes or pairs of genes could be affected by treatments for X-linked Dystonia-Parkinsonism, a rare inherited neurodegenerative disorder.
“Our ultimate goal is to create a clear road map of possible ways to reverse disease at the cellular level,” Zitnik said.
Authorship, funding, disclosures
Additional authors include Guadalupe Gonzalez, Xiang Lin, Isuru Herath, Kirill Veselkov, and Michael Bronstein.
The work was funded in part by federal grants (NIH grant R01-HD108794, NSF CAREER 2339524, and US DoD FA8702-15-D-0001), ARPA-H BDF program, awards from the Chan Zuckerberg Initiative, the Gates Foundation INV-079038, Amazon Faculty Research, Google Research Scholar Program, AstraZeneca Research, Roche Alliance with Distinguished Scientists, Sanofi iDEA-iTECH, Pfizer Research, John and Virginia Kaneb Fellowship at HMS, Biswas Computational Biology Initiative in partnership with the Milken Institute, HMS Dean’s Innovation Awards for the Use of Artificial Intelligence, Harvard Data Science Initiative, and the Kempner Institute for the Study of Natural and Artificial Intelligence at Harvard University. Partial support was received from the Summer Institute in Biomedical Informatics at HMS and from the ERC-Consolidator Grant No. 724228.
Gonzalez is currently employed by Genentech, Inc., and Herath was employed by Merck & Co., Inc. during the study.
END
New AI tool pinpoints genes, drug combos to restore health in diseased cells
New model could optimize drug discovery
2025-09-09
ELSE PRESS RELEASES FROM THIS DATE:
Predicting where deadly brain cancer may spread next
2025-09-09
Glioblastoma is a devastatingly effective brain cancer. Doctors can cut it out or blast it with radiation, but that only buys time. The cancer has an insidious ability to hide enough tumor cells in tissue around the tumor to allow it to return as deadly as ever.
Patients diagnosed with glioblastoma survive for an average of 15 months.
What’s needed is a better way of identifying those hidden cancer cells and predicting where the tumor might grow next. Jennifer Munson believes she and her research team at the Fralin Biomedical Research Institute at VTC have developed a tool to do just that.
Their method, described ...
First ever measure of boron in individual cancer cells could revolutionise drug understanding
2025-09-09
A new technique has measured boron in individual cancer cells for the first time, enabling researchers to better understand how drugs act to kill tumours in some cancers.
In a new article in the Journal of Analytical Atomic Spectrometry, a team from the University of Birmingham funded by the Rosetrees Trust have for the first time used a technology to conduct real-time measurement of boron in live tumour cells. The technique, called single-cell ICP-MS, enabled the team to see how and when treatments for head and neck cancers enter and exit tumour cells.
Boron Neutron Capture Therapy (BNCT) is a new form of therapeutic for head and neck cancer that involves ...
Graz researchers discover what stiffens the aorta
2025-09-09
Cardiovascular diseases remain the most common cause of death worldwide. In Europe, they account for over 40 percent of all deaths. However, known risk factors such as high cholesterol levels or high blood pressure cannot fully explain the high mortality rate or the number of cardiovascular diseases. Scientists in Graz have now investigated a new factor that is closely linked to cardiovascular mortality. Elevated levels of the amino acid homocysteine in the blood led to a stiffer and less elastic aorta in an animal model. These findings contribute to the current understanding ...
Breakthrough in atomic-level etching of hafnium oxide, a promising material for advanced semiconductors
2025-09-09
Hafnium oxide (HfO2) has attracted attention as a promising material for ultrathin semiconductors and other microelectronic devices. The strong ionic bond between hafnium and oxygen atoms in HfO2 gives it a high dielectric constant, superior thermal stability, and a wide band gap.
Notably, these properties can be maintained even at the atomic scale. Meanwhile, these properties also pose challenges in achieving highly precise and smooth etching of HfO2 films.
Now, a group of researchers from Japan and Taiwan has successfully etched HfO2 films with atomic-level precision, smoothness, ...
How evolution explains autism rates in humans
2025-09-09
A new paper in Molecular Biology and Evolution, published by Oxford University Press, finds that the relatively high rate of Autism-spectrum disorders in humans is likely due to how humans evolved in the past.
About one in 31 (3.2%) children in the United States has been identified with Autism Spectrum Disorder. Globally, the World Health Organization estimates that around one in 100 children have autism. From an evolutionary perspective, many scientist believe that autism and schizophrenia may be unique to humans. ...
Swedish psychologist transforms mental health access through digital therapy revolution
2025-09-09
LINKÖPING, SWEDEN, 9 September 2025 -- In a revealing Genomic Press Interview published today in Genomic Psychiatry, Dr. Gerhard Andersson traces his extraordinary journey from skateboarding punk musician to becoming the architect of a global revolution in psychological treatment delivery. The comprehensive interview unveils how two graduate students knocking on his office door in 1998 sparked a transformation that would fundamentally alter how millions access mental healthcare worldwide.
From Uppsala Laboratory to Global Impact
Dr. Andersson's path to scientific prominence began unexpectedly ...
Centenarian neuroscientist inspires blueprint for vibrant longevity through mentorship and connection
2025-09-09
TUCSON, Arizona, USA, 9 September 2025 -- A viewpoint article published today in Brain Medicine by Dr. Esther Sternberg provides a compelling portrait of how one pioneering neuroscientist continues to thrive beyond his centennial year. The tribute to Dr. Seymour Reichlin, published as part of a special Festschrift commemorating his 100th birthday, examines the multifaceted elements that have sustained his remarkable intellectual vigor and social vitality at 101 years old.
Dr. Sternberg, who has directed research at the Andrew Weil Center for Integrative ...
King’s College London researcher advances psychiatric genomics through pioneering polygenic scoring innovations
2025-09-09
LONDON, England, UNITED KINGDOM, 9 September 2025 -- In a compelling Genomic Press Interview published today in Genomic Psychiatry, Dr Oliver Pain reveals how personal experiences and scientific curiosity converged to reshape global approaches to psychiatric genomics. The Sir Henry Wellcome Postdoctoral Research Fellow transforms how scientists worldwide understand and apply genetic risk prediction for mental health disorders, developing tools that democratize access to cutting-edge genomic methodologies across international research communities.
The interview illuminates Dr Pain's evolution ...
Study questions ocean origin of organics in Enceladus’s plumes
2025-09-09
Organic molecules detected in the watery plumes that spew out from cracks in the surface of Enceladus could be formed through exposure to radiation on Saturn’s icy moon, rather than originating from deep within its sub-surface ocean. The findings, presented during the EPSC–DPS2025 Joint Meeting in Helsinki this week, have repercussions for assessing the habitability of Enceladus’s ocean.
‘While the identification of complex organic molecules in Enceladus’s environment remains an important clue in assessing the moon’s habitability, the results demonstrate that radiation-driven chemistry ...
Look out for the keyhole: How to find the safest spots to deflect a hazardous asteroid
2025-09-09
Selecting the right spot to smash a spacecraft into the surface of a hazardous asteroid to deflect it must be done with great care, according to new research presented at the EPSC-DPS2025 Joint Meeting this week in Helsinki. Slamming into its surface indiscriminately runs the risk of knocking the asteroid through a 'gravitational keyhole' that sends it back around to hit Earth at a later date.
"Even if we intentionally push an asteroid away from Earth with a space mission, we must make sure it doesn't drift into one of these ...
LAST 30 PRESS RELEASES:
Scientists create ChatGPT-like AI model for neuroscience to build one of the most detailed mouse brain maps to date
AI and omics unlock personalized drugs and RNA therapies for heart disease
2023 ocean heatwave ‘unprecedented but not unexpected’
Johns Hopkins researchers develop AI to predict risk of US car crashes
New drug combination offers hope for men with advanced prostate cancer
New discovery finds gene converts insulin-producing cells into blood-sugar boosters
Powerful and precise multi-color lasers now fit on a single chip
Scientists agree chemicals can affect behavior, but industry workers more reluctant about safety testing
DNA nanospring measures cellular motor power
Elsevier Foundation and RIKEN launch “Envisioning Futures” report: paving the way for gender equity and women’s leadership in Japanese research
Researchers discover enlarged areas of the spinal cord in fish, previously found only in four-limbed vertebrates
Bipolar disorder heterogeneity decoded: transforming global psychiatric treatment approaches
Catching Alport syndrome through universal age-3 urine screening
Instructions help you remember something better than emotions or a good night’s sleep
Solar energy is now the world’s cheapest source of power, a Surrey study finds
Scientists reverse Alzheimer’s in mice using nanoparticles
‘Good’ gut bacteria boosts placenta for healthier pregnancy
USC team demonstrates first optical device based on “optical thermodynamics”
Microplastics found to change gut microbiome in first human-sample study
Artificially sweetened and sugary drinks are both associated with an increased risk of liver disease, study finds
Plastic in the soil, but not as we know it: Biodegradable microplastics rewire carbon storage in farm fields
Yeast proteins reveal the secrets of drought resistance
Psychiatry, primary care, and OB/GYN subspecialties hit hardest by physician attrition
New Canadian study reveals where HIV hides in different parts of the body
Lidocaine poisonings rise despite overall drop in local anesthetic toxicity
Politics follow you on the road
Scientists blaze new path to fighting viral diseases
The mouse eye as a window to spotting systemic disease
AI and the Future of Cancer Research and Cancer Care to headline October 24 gathering of global oncology leaders at the National Press Club: NFCR Global Summit to feature top scientists, entrepreneurs
FDA clears UCLA heart tissue regeneration drug AD-NP1 for clinical trials
[Press-News.org] New AI tool pinpoints genes, drug combos to restore health in diseased cellsNew model could optimize drug discovery