An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges

Karamarie Fecho^{1

2}, Chris Bizon¹, Tursynay Issabekova³, Sierra Moxon⁴, Anne E Thessen³, Shervin Abdollahi⁵, Sergio E Baranzini⁶, Basazin Belhu⁷, William E Byrd⁸, Lawrence Chung⁹, Andrew Crouse⁸, Marc P Duby⁹, Stephen Ferguson¹⁰, Aleksandra Foksinska⁸, Laura Forero^{11

12}, Jennifer Friedman^{11

12}, Vicki Gardner¹, Gwênlyn Glusman⁷, Jennifer Hadlock⁷, Kristina Hanspers¹³, Eugene Hinderer¹⁴, Charlotte Hobbs¹¹, Gregory Hyde¹⁵, Sui Huang⁷, David Koslicki¹⁶, Philip Mease^{17

18}, Sandrine Muller⁹, Christopher J Mungall⁴, Stephen A Ramsey¹⁹, Jared Roach⁷, Irit Rubin⁷, Shepherd H Schurman²⁰, Anath Shalev⁸, Brett Smith⁷, Karthik Soman⁶, Sarah Stemann⁵, Andrew I Su²¹, Casey Ta²², Paul B Watkins²³, Mark D Williams⁵, Chunlei Wu²¹, Colleen H Xu²¹; Biomedical Data Translator Consortium

Affiliations

¹ Renaissance Computing Institute (RENCI), University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² Copperline Professional Solutions, Pittsboro, NC, USA.
³ Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴ Biosystems Data Science Department, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
⁵ Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
⁶ Department of Neurology, Weill Institute for Neuroscience, University of California - San Francisco, San Francisco, CA, USA.
⁷ Institute for Systems Biology, Seattle, WA, USA.
⁸ The Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, Birmingham, AL, USA.
⁹ The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
¹¹ Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA, USA.
¹² University of California at San Diego, San Diego, CA, USA.
¹³ Gladstone Institutes, University of California - San Francisco, San Francisco, CA, USA.
¹⁴ Tufts Clinical and Translational Science Institute, Tufts Medical Center, Boston, MA, USA.
¹⁵ Thayer School of Engineering at Dartmouth College, Hanover, NH, USA.
¹⁶ Departments of Computer Science and Engineering, Biology, and the Huck Institutes of the Life Sciences, Penn State University, University Park, PA, USA.
¹⁷ Swedish Medical Center, St. Joseph Health, Seattle, WA, USA.
¹⁸ University of Washington, Seattle, WA, USA.
¹⁹ Oregon State University, Corvallis, OR, USA.
²⁰ National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
²¹ The Scripps Research Institute, La Jolla, CA, USA.
²² Columbia University Irving Medical Center, New York, NY, USA.
²³ Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

PMID: 37900350
PMCID: PMC10603356
DOI: 10.1017/cts.2023.619

An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges

Karamarie Fecho et al. J Clin Transl Sci. 2023.

. 2023 Sep 14;7(1):e214.

doi: 10.1017/cts.2023.619. eCollection 2023.

Authors

Affiliations

¹ Renaissance Computing Institute (RENCI), University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² Copperline Professional Solutions, Pittsboro, NC, USA.
³ Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴ Biosystems Data Science Department, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
⁵ Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
⁶ Department of Neurology, Weill Institute for Neuroscience, University of California - San Francisco, San Francisco, CA, USA.
⁷ Institute for Systems Biology, Seattle, WA, USA.
⁸ The Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, Birmingham, AL, USA.
⁹ The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
¹¹ Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA, USA.
¹² University of California at San Diego, San Diego, CA, USA.
¹³ Gladstone Institutes, University of California - San Francisco, San Francisco, CA, USA.
¹⁴ Tufts Clinical and Translational Science Institute, Tufts Medical Center, Boston, MA, USA.
¹⁵ Thayer School of Engineering at Dartmouth College, Hanover, NH, USA.
¹⁶ Departments of Computer Science and Engineering, Biology, and the Huck Institutes of the Life Sciences, Penn State University, University Park, PA, USA.
¹⁷ Swedish Medical Center, St. Joseph Health, Seattle, WA, USA.
¹⁸ University of Washington, Seattle, WA, USA.
¹⁹ Oregon State University, Corvallis, OR, USA.
²⁰ National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
²¹ The Scripps Research Institute, La Jolla, CA, USA.
²² Columbia University Irving Medical Center, New York, NY, USA.
²³ Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

PMID: 37900350
PMCID: PMC10603356
DOI: 10.1017/cts.2023.619

Abstract

Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph-based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly "Question-of-the-Month (QotM) Challenge" series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.

Keywords: Translational research; bioinformatics; knowledge graphs; semantic technology; team science.

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Conflict of interest statement

JF receives additional funding from the Rady Children’s Institute for Genomic Medicine, and her spouse is Founder and Principal of Friedman Bioventure. JH receives grant/contract support (paid to institution) from: Pfizer; Novartis; Janssen; BMS; and Gilead. PJM receives grant/research support from: AbbVie; Amgen; Bristol Myers Squibb; Eli Lilly; Galapagos; Gilead; Janssen; Novartis; Pfizer; Sun Pharma; and UCB. PJM also serves as a consultant at: AbbVie; Acelyrin; Aclaris; Amgen; Boehringer Ingelheim; Bristol Myers Squibb; Eli Lilly; Galapagos; Gilead; GlaxoSmithKline; Inmagene; Janssen; Pfizer; Moonlake Pharma; Novartis; Sun Pharma; and UCB. In addition, PJM receives speakers’ bureau fees from: AbbVie; Amgen; Eli Lilly; Janssen; Novartis; Pfizer; and Union Chimique Belge. SHS is supported by the National Institute on Aging, Intramural Research Program. All other primary authors have no conflicts of interest to declare.

Figures

**Figure 1.**
Structure of the question-of-the-month (QotM) challenge series. h = hours; min = minutes.

**Figure 2.**
Example of a Translator answer subgraph demonstrating a relationship between liver disease and a set of genes associated specifically with inherited porphyria: *ALAS1; ALAS2*; *ALAD*; *PPOX*; *HMBS;* and *UROD*.

See this image and copyright information in PMC

References

1. The Alan Turing Institute, Interest Group. Knowledge graphs. How do we encode knowledge to use at scale in open, evolving, decentralized systems? 2023. https://www.turing.ac.uk/research/interest-groups/knowledge-graphs. Accessed July 10, 2023.
1. The Biomedical Data Translator Consortium. Toward a universal biomedical data translator. Clini Translat Sci. 2019;12(2):91–94. doi: 10.1111/cts.13021. - DOI - PMC - PubMed
1. Fecho K, Thessen AE, Baranzini SE, The Biomedical Data Translator Consortium, et al. Progress toward a universal biomedical data translator. Clin Translat Sci. 2022;15(8):1838–1847. doi: 10.1111/cts.13301. - DOI - PMC - PubMed
1. Fecho K, Thessen AE, Baranzini SE, The Biomedical Data Translator Consortium, et al. Sex, obesity, diabetes, and exposure to particulate matter: scientific insights revealed by analysis of open clinical data sources during a five day hackathon. J Biomed Inform. 2019;100:103325. doi: 10.1016/j.jbi.2019.103325. - DOI - PMC - PubMed
1. Fecho K, Balhoff J, Bizon C, et al. Application of MCAT questions as a testing tool and evaluation metric for knowledge graph-based reasoning systems. Clin Translat Sci. 2021;14(5):1719–1724. doi: 10.1111/cts.13021. - DOI - PMC - PubMed

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An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges

Affiliations

An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources