Welcome to hegroup.org!

Welcome to the home page of Dr. Yongqun "Oliver" He's laboratory research group at the University of Michigan Medical School, Ann Arbor, MI, USA!

Our group has now focused on computational medicine and bioinformatics research, with primary research interests in the areas of vaccinology, host-pathogen interactions, nephrology, ontology, literature mining, and machine learning. Our primary scientific research domains are microbiology, vaccinology, and nephrology. Our primary technical research is artificial intelligence (AI), with a focus on ontology, semantic web, literature mining, and machine learning. We are also interested in applying our technologies to other interesting areas as well.

News: Currently we are recruiting a Software Developer / Bioinformatician, and a Postdoctoral fellow. Welcome to forward or apply!

A brief introduction of our research is provided below:

(1) Development and applications of community-based ontologies and ontology tools. Ontologies have emerged to become critical to biomedical data and knowledge integration, sharing and validation, as well as new knowledge discovery. A major field of AI is knowledge representation and reasoning (KR², KR&R), and ontology is a major part of KR&R.

We have (co-)initiated and (co-)led the development of many community-based ontologies such as the Vaccine Ontology (VO) and Cell Line Ontology (CLO). Dr. He is also an active developer of the Cell Ontology (CL) and Ontology for Biomedical Investigations (OBI). OBI is collaboratively developed by over 20 communities, and Dr. He is the representation of the vaccine community.

We have developed many widely used ontology tools (e.g., Ontobee, Ontofox, Ontodog, and Ontorat), collectively names “Ontoanimal” tools. Each tool has specific functions; together, these tools are able to extract ontology subsets, provide ontology community views, generate and edit ontology terms, query and visualize ontology terms, provide statistics of ontologies, and compare ontologies. We have also initiated the proposal of the eXtensible ontology development (XOD) principles and methods to support ontology interoperability. With the XOD and our Ontoanimal tools, ontology development is no longer boring and has become more fun and useful!

As a major social activity, Oliver hosted and co-chaired the 2022 International Conference on Biomedical Ontology (ICBO-2022) in September 2022 at the University of Michigan, Ann Arbor, MI, USA.

(2) Vaccine Informatics: Vaccine knowledgebase, vaccine mechanism, vaccine design, and safety analysis

Dr. He is one of the pioneers in the field of Vaccine Informatics, a branch of vaccinology aimed to develop and apply informatics to study vaccines. He and his collaborators Drs. Rino Rappuoli, Anne S. De Groot, and Robert T. Chen initiated a special issue on vaccine informatics in 2010. Motivated from his Brucella vaccine PhD research (during 1996 - 2000) and his skilled by his later computer science and bioinformatics training, Dr. He has been actively conducting research in the field for over 20 years.

We developed VIOLIN, the most comprehensive vaccine database and analysis system. The Vaccine Ontology (VO) has become a community effort for standard representation of vaccines, vaccine components, vaccination, and host responses to vaccines. We have also developed Vaxign and Vaxign2, the first web-based publically available vaccine target design tool based on bioinformatics analysis of genome sequences using the strategy of reverse vaccinology. We have also developed Vaxign-ML, a supervised machine learning model to support vaccine design. We have also used these tools to predict COVID-19 vaccine candidates.

News: On August 19, 2022, Dr. Oliver He and his collaborators were awarded a 5-year NIH U24 grant entitled "VIOLIN 2.0: Vaccine Information and Ontology LInked kNowledgebase" (U24AI171008). Congratulations!

(3) Kidney Precision Medicine

Dr. He has been working since 2017 as a co-investigator on the Kidney Precision Medicine Project (KPMP), a NIDDK-funded ambitious project with the purpose of understanding and finding new ways to treat acute kidney injury (AKI) and chronic kidney disease (CKD). KPMP has involved over 20 universities and hospitals with patient representatives, researchers, and clinicians, committed to meet the needs of the kidney disease community.

To support seamless integration of heterogeneous clinical, pathological, and molecular kidney precision medicine knowledge and data, Dr. He has led the development and applications of the community-based Kidney Tissue Atlas Ontology (KTAO) and Ontology of Precision Medicine Investigation (OPMI). A more general description of the usage of ontology for kidney precision medicine research is available in our review article in Nature Reviews Nephrology.

(4) Microbiology: Brucellosis, COVID-19, and Host-pathogen interactions

To better study host-pathogen interactions, we developed PHIDIAS, the most comprehesenive host-pathogen interaction database focusing on human and animal pathogens. As part of PHIDIAS, we have developed Victors, a comprehensive knowledge base of more than 3,000 virulence factors in >120 human and animal pathogens. We have also developed an Ontology of Host-Pathogen Interactions (OHPI) to logically represent the virulence factors and their interactions with the hosts.

Our major pathogen research model is Brucella, an intracellular bacterium that causes zoonotic brucellosis in humans and a variety of animals such as goat, sheep, pigs, and dogs. Dr. He conducted his PhD research on brucellosis with his PhD mentor Dr. Gerhardt G. Schurig at Virginia Tech. Dr. He's own laboratory in Michigan has also conducted productive web-lab and dry-lab brucellosis research.

To address the challenge of the COVID-19 pandemic, we have conducted active COVID-19 research with 30 journal article published. In early 2020, Dr. He co-initiated the development of the community-driven Coronavirus Infectious Disease Ontology (CIDO, see the CIDO paper in Scientifc Data). We developed a COVID-19 vaccine knowledgebase (Cov19VaxKB). We also utilized reverse vaccinology and mechine learning methods to predict COVID-19 vaccine antigens. During 2020-2021, Dr. He served as a faculty member on the President's and Provost's COVID-19 Faculty Council in the University of Michigan. Dr. He also hired >20 undergraduates to conduct productive COVID-19 research, reflecting our commitment to research, education, and public health service.

(5) Systematic modeling and analysis of biological interaction networks

We hypothesized that ontology supports literature mining and analysis of biological interaction networks. As a result, we developed the Interaction Network Ontology (INO) and applied it to enhance literature mining performance. We are also collaborating with our collaborators, including Drs. Junguk Hur, Arzugan Özgür, and Dr. Cui Tao, to apply ontology for more advanced literature mining.

Bayesian network (BN) can model linear, nonlinear, combinatorial, and stochastic relationships among variables across multiple levels of biological organizations. We have developed new BN algorithms and tools for analysis of gene interaction networks using high throughput gene expression data.

In a 2014 paper (He, 2014) and then a 2016 paper (He, 2016), Dr. He proposed a new “OneNet Theory of Life”. The OneNet theory states that the whole process of a life of an organism is a single complex and dynamic network (called “OneNet”). Dr. He also proposes OneNet tenets to characterize different aspects of the OneNet life. Ontologies and ontology-based bioinformatics tools, such as those introduced above, can be used to integratively represent and study such OneNet theory and OneNet knowledge of different organisms.

(6) Wet-lab (not active now): Host-Brucella interaction and protective vaccine immune mechanisms.

Dr. Oliver He has strong backgrounds in wet-lab microbiology and immunology research. In his M.S. wet-lab research (1993-1996), he developed a new ELISA method, applied the method for epidemiological survey of avian reticuloendotheliosis virus (REV, a RNA virus) outbreak in China, and for the first time found its wide existance in North China. His Ph.D. thesis research focused on vaccine development and immune mechanism against brucellosis. After Dr. He joined the University of Michigan in 2005, we continued the Brucella vaccine research in He lab. One major finding out of our wet-lab studies is the identification of a unique caspase-2-mediated proinflammatory cell death mechanism, which was first observed in our laboratory in macrophages infected with Brucella cattle vaccine RB51 and other rough Brucella strains (but not virulent wild type Brucella strains) (References: He et al, 2006, Chen and He, 2009, Chen et al, 2011, Li and He, 2012, Bronner et al, 2013, and Bronner et al, 2015). Our research has also made Brucella a good model system to study caspase-2 related roles and pathways.

More details about our projects can be found here.

Your suggestions, comments, and collaborations are welcome. Thank you!