Promoting validation and cross-phylogenetic integration in model organism research

Keith C Cheng^{1

2}, Rebecca D Burdine³, Mary E Dickinson^{4

5}, Stephen C Ekker⁶, Alex Y Lin¹, K C Kent Lloyd^{7

8}, Cathleen M Lutz⁹, Calum A MacRae¹⁰, John H Morrison^{11

12}, David H O'Connor¹³, John H Postlethwait¹⁴, Crystal D Rogers¹⁵, Susan Sanchez¹⁶, Julie H Simpson¹⁷, William S Talbot¹⁸, Douglas C Wallace¹⁹, Jill M Weimer²⁰, Hugo J Bellen²¹

Affiliations

¹ Department of Pathology, Penn State College of Medicine, Hershey, PA 17033, USA.
² Institute for Computational and Data Sciences, Pennsylvania State University, Park, PA 16802, USA.
³ Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
⁴ Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77007, USA.
⁵ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77007, USA.
⁶ Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55906, USA.
⁷ Mouse Biology Program, School of Medicinel, University of California Davis, Davis, CA 95618, USA.
⁸ Department of Surgery, School of Medicine, University of California Davis, Davis, CA 95618, USA.
⁹ The Jackson Laboratory, Genetic Resource Science, Bar Harbor, ME 04609, USA.
¹⁰ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 360 Longwood Avenue, Boston, MA 02215, USA.
¹¹ California National Primate Research Center, University of California Davis, Davis, CA 95616, USA.
¹² Department of Neurology, University of California Davis, Davis, CA 95616, USA.
¹³ Department of Pathology and Laboratory Medicine, University ofWisconsin-Madison, Madison, WI 53711, USA.
¹⁴ Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.
¹⁵ School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA.
¹⁶ Department of Infectious Diseases, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, USA.
¹⁷ Department of Molecular, Cell and Developmental Biology, University of California, Santa Barbara, CA 93117, USA.
¹⁸ Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
¹⁹ Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
²⁰ Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD 57104, USA.
²¹ Department of Molecular and Human Genetics, Neurological Research Institute (TCH), Baylor College of Medicine, Houston, TX 77007, USA.

PMID: 36125045
PMCID: PMC9531892
DOI: 10.1242/dmm.049600

Promoting validation and cross-phylogenetic integration in model organism research

Keith C Cheng et al. Dis Model Mech. 2022.

. 2022 Sep 1;15(9):dmm049600.

doi: 10.1242/dmm.049600. Epub 2022 Sep 20.

Authors

Affiliations

¹ Department of Pathology, Penn State College of Medicine, Hershey, PA 17033, USA.
² Institute for Computational and Data Sciences, Pennsylvania State University, Park, PA 16802, USA.
³ Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
⁴ Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77007, USA.
⁵ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77007, USA.
⁶ Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55906, USA.
⁷ Mouse Biology Program, School of Medicinel, University of California Davis, Davis, CA 95618, USA.
⁸ Department of Surgery, School of Medicine, University of California Davis, Davis, CA 95618, USA.
⁹ The Jackson Laboratory, Genetic Resource Science, Bar Harbor, ME 04609, USA.
¹⁰ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 360 Longwood Avenue, Boston, MA 02215, USA.
¹¹ California National Primate Research Center, University of California Davis, Davis, CA 95616, USA.
¹² Department of Neurology, University of California Davis, Davis, CA 95616, USA.
¹³ Department of Pathology and Laboratory Medicine, University ofWisconsin-Madison, Madison, WI 53711, USA.
¹⁴ Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.
¹⁵ School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA.
¹⁶ Department of Infectious Diseases, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, USA.
¹⁷ Department of Molecular, Cell and Developmental Biology, University of California, Santa Barbara, CA 93117, USA.
¹⁸ Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
¹⁹ Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
²⁰ Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD 57104, USA.
²¹ Department of Molecular and Human Genetics, Neurological Research Institute (TCH), Baylor College of Medicine, Houston, TX 77007, USA.

PMID: 36125045
PMCID: PMC9531892
DOI: 10.1242/dmm.049600

Abstract

Model organism (MO) research provides a basic understanding of biology and disease due to the evolutionary conservation of the molecular and cellular language of life. MOs have been used to identify and understand the function of orthologous genes, proteins, cells and tissues involved in biological processes, to develop and evaluate techniques and methods, and to perform whole-organism-based chemical screens to test drug efficacy and toxicity. However, a growing richness of datasets and the rising power of computation raise an important question: How do we maximize the value of MOs? In-depth discussions in over 50 virtual presentations organized by the National Institutes of Health across more than 10 weeks yielded important suggestions for improving the rigor, validation, reproducibility and translatability of MO research. The effort clarified challenges and opportunities for developing and integrating tools and resources. Maintenance of critical existing infrastructure and the implementation of suggested improvements will play important roles in maintaining productivity and facilitating the validation of animal models of human biology and disease.

Keywords: Human diseases; Integration; Model organisms; Omics; Phenomics; Research resources; Technology; Validation.

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Conflict of interest statement

Competing interests The authors declare no competing or financial interests.

Figures

**Fig. 1.**
**‘Vertical integration’ facilitates collaborative research between scientists and clinicians with shared interests.** Four different scenarios of vertical integration discussed in the main text are depicted here. The logos of MARRVEL, Monarch Initiative, Alliance of Genome Resources, ModelMatcher, Matchmaker Exchange and GeneMatcher were obtained from respective websites. FDA, U.S. Food and Drug Administration; MO, model organism.

See this image and copyright information in PMC

References

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Promoting validation and cross-phylogenetic integration in model organism research

Affiliations

Promoting validation and cross-phylogenetic integration in model organism research

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources