Augmented Cancer Care of the Future

In the future, determining customized care for cancer treatment may occur at the click of a mouse. Dr. Ratul Chowdhury is working on a computational design that enables artificial intelligence to decipher the molecular details of individual protein structures, which can inform personalized treatment plans.

“While we know structures contain approximately two million proteins, it is just barely scratching the surface of all possible proteins that exist,” says Dr. Chowdhury. “We have only very recently started to deploy sophisticated computing strategies to parse the language rules that govern shape-directed protein function with a consequence in diseases such as cancer.”

Dr. Ratul Chowdhury joined the Chemical & Biological Engineering Department at Iowa State University as an Assistant Professor in the Fall of 2022. He is also a member of the Nanovaccine Institute. His work is cross-disciplinary and touches on drug design, bio-aware machine learning, biomaterials, green chemistry, and protein design.

Small changes in existing proteins within the human body can likely lead to cancerous states. These changes manifest as the alteration of a few amino acids in a protein, thereby deforming the protein structure. Subsequently, the cellular operations affiliated with those proteins are affected and can potentially lead to a cancerous state which then thrives. Dr. Chowdhury and his lab use protein language models to identify the importance of each amino acid sequence of proteins and thus track structure changes that occur when one or few amino acids change.

Dr. Chowdhury likens the process to understanding a new language without a dictionary.

“If I were to give you to memorize a book of millions of sentences – and you do not know the language – memorization will implicitly make you learn the grammar that dictates the permitted order of words in these sentences,” says Dr. Chowdhury. “Not only this, but you would then ideally be able to write new, correct sentences, which are not present in the book but preserve the grammar.”

While language modeling of proteins has broad applications to human diseases, cancer is an area where its use can have significant benefits. With cancer, intervention strategies are not necessarily scalable or transferable from patient to patient, but artificial intelligence is likely to emerge as a therapeutic tool in the hands of a clinical specialist to determine treatment options for a patient in the years to come. This approach would not replace the expertise and insights of clinicians. Rather, it would streamline their work in solving medical puzzles.

“Variability in biology is quite high, and quantifying that variability is not trivial,” says Dr. Chowdhury. “Focused computational strategies can extend a clinician’s ability to manage a disease that has devastating impacts in society.”

Dr. Chowdhury’s lab at Iowa State University comprises nine members, including post-doctorates, graduate students, and undergraduate research fellows working on various computational projects. Dr. Chowdhury emphasizes student training and mentorship in his work to encourage a future generation of accomplished scientists. A visit to Dr. Chowdhury’s lab page shows a long thread of news and updates emphasizing student achievements and engagement.?

“I was aware of the research at Iowa State since I was a graduate student at Penn State,” says Dr. Chowdhury. “The Nanovaccine Institute stands tall with a wide spectrum of experimental biology in therapeutics, and we are fortunate to find ourselves in this extremely collaborative setting.”

Dr. Chowdhury’s work was recently published in a 2023 publication of Nature Biotechnology, one of the topmost journals in this area of research. The article “Single-sequence protein structure prediction using a language model and deep learning” introduces a major advancement in a protein language model, recurrent geometric network (RGN2), for protein structure prediction. To access the article, please visit Nature Biotechnology.

To learn more about Dr. Ratul Chowdhury, please visit the Nanovaccine Institute website.??