Cheriton School of Computer Science Professor Bin Ma has been appointed a University Research Chair to recognize his outstanding contributions to bioinformatics, in particular his development of novel algorithms and software to derive biological information from DNA and proteins.
University Research Chairs are prestigious appointments conferred by the University of Waterloo. They are held for up to seven years and are awarded to acknowledge exceptional achievements of faculty members and to recognize their pre-eminence in a field of knowledge. This is the second time Professor Ma has been appointed a University Research Chair.
“Congratulation to Bin on his appointment as a University Research Chair,” said Raouf Boutaba, Professor and Director of the Cheriton School of Computer Science. “Bin has brought the lens of a computer scientist to the field of bioinformatics through his influential contributions to genomics and proteomics, both of which are the foundation for novel disease diagnosis and treatment.”
Professor Ma has made many ground-breaking discoveries in bioinformatics, of which three in particular stand out — within genomics, a method to quickly decipher the order of similar nucleotide sequences in DNA, and within proteomics, development of software that uses data from mass spectrometry to determine the sequence of amino acids in peptides, as well as development of a next-generation high-throughput platform to sequence proteins.
Inventing the spaced seed method
Within genomics, Professor Ma and his collaborators invented in 2002 a technique, called the spaced seed method, to optimize the speed and sensitivity at which strands of DNA are sequenced. Much like a search engine for the Internet, the sequence similarity search helps find related nucleotide sequences in DNA databases. A quick and sensitive search is particularly important because of the huge growth in the size of genomic databases. To gain speed, traditional algorithms have sacrificed sensitivity. The spaced seed method, however, employs a mathematically rigorous algorithm that uses the matches at several pre-determined positions to trigger a similarity comparison.
Professor Ma and his coauthors proved mathematically and demonstrated empirically that the trade-off between search speed and sensitivity can be dramatically improved. He and his colleagues founded a new research area in bioinformatics that optimizes and applies spaced seeds. His original paper on spaced seeds has been cited more than a thousand times, and the method has become one of three standard DNA search algorithms employed by the BLAST search engine used daily by thousands of clinicians and scientists.
Developing the standard software to sequence peptides
Amino acids are the building blocks of peptides and ultimately proteins. By convention, amino acids are labelled using a one-letter code, so a protein’s sequence of amino acids can be considered as a word composed of letters. The process of determining the sequence of these letters that correspond to an unknown protein or peptide molecule — what’s known as de novo sequencing — is an essential task in proteomics. The challenge, however, is that traditional sequencing methods are slow and labour intensive.
Advances in mass spectrometry technology, a commonly used analytical technique to determine the mass, structure and chemical properties of molecules, renewed hope for de novo peptide sequencing. Professor Ma was among the first bioinformaticians working on this important problem. In 2003, he invented a novel algorithm and developed a software package called PEAKS that enables high-throughput de novo peptide sequencing using mass spectrometry data. PEAKS has been adopted by more than a thousand proteomics research labs and it is an indispensable tool that allows researchers to develop new diagnostic tests and treatments for disease.
Pioneering the next-generation protein sequencing technology
Sequencing large protein molecules is far more difficult than sequencing short peptides. Consequently, the lack of a high-throughput de novo protein sequencing method has limited the potential of proteomics. Under Professor Ma’s leadership, a next-generation high-throughput protein sequencing platform, called REmAb, was successfully developed.
The technique first requires that a protein molecule be cut into pieces using proteases, enzymes that break down proteins into shorter amino acid sequences known as peptides. After sequencing each of the peptides, the peptide sequences are assembled to obtain the protein’s amino acid sequence. However, novel assembling and error-correcting algorithms are needed to deal with the unavoidable high rates of error in mass spectrometry data. Mass spectrometry also needs to be specially performed to ensure sufficient data is available regardless of the protein being sequenced. Using several innovations in experiments and analytical algorithms, the REmAb platform is able to perform accurate, high-throughput de novo protein sequencing.
This next-generation protein sequencing technology has already helped health and pharmaceutical researchers in a number of applications — from reviving lost antibody-producing cell lines, to discovering new antibodies in blood, to identifying the antibodies from certain kinds of blood cancers. Recently, Professor Ma and his team used their REmAb sequencing technology to help other researchers identify antibodies from the blood of convalescent COVID-19 patients with the hope of using the antibodies to develop new treatments.
Professor Ma received his PhD from Beijing University in 1999. After a postdoctoral fellowship at the University of Waterloo, he was appointed as an Assistant Professor and Canada Research Chair at Western University. He joined the Cheriton School of Computer Science in 2008 as an Associate Professor and was promoted to Professor in 2011. As of May 2021, his publications have been cited collectively 20,195 times. His many recognitions include being named an inaugural Wes Graham Research Fellow (2017–2020) receiving the 2010 Outstanding Young Computer Science Researcher by CS-Can | Info-Can, receiving a Premier’s Catalyst Award for Best Young Innovator in 2009, and the Premier’s Research Excellence Award in 2003.
Professor Ma is the tenth faculty member at the Cheriton School of Computer Science to be appointed a University Research Chair. Other faculty members who have been appointed University Research Chairs are Professors Shai Ben-David (2020), Kate Larson (2019), Raouf Boutaba (2018), Lila Kari (2015), Ian Goldberg (2012), Bin Ma (2008), Timothy Chan (2005), Doug Stinson (2005), and M. Tamer Özsu (2004). Professor Ma’s appointment to a second seven-year term begins on July 1, 2021.
