The TiHoCL panel for canine lymphoma: a feasibility study integrating functional genomics and network biology approaches for comparative oncology targeted NGS panel design

Silvia Fibi-Smetana; Camila Inglis; Daniela Schuster; Nina Eberle; José Luis Granados-Soler; Wen Liu; Saskia Krohn; Christian Junghanss; Ingo Nolte; Leila Taher; Hugo Murua Escobar

doi:10.3389/fvets.2023.1301536

The TiHoCL panel for canine lymphoma: a feasibility study integrating functional genomics and network biology approaches for comparative oncology targeted NGS panel design

Front Vet Sci. 2023 Dec 8:10:1301536. doi: 10.3389/fvets.2023.1301536. eCollection 2023.

Authors

Silvia Fibi-Smetana¹, Camila Inglis^{2

3}, Daniela Schuster^{4

5}, Nina Eberle², José Luis Granados-Soler^{2

6}, Wen Liu³, Saskia Krohn³, Christian Junghanss³, Ingo Nolte², Leila Taher^{1

3

4

5}, Hugo Murua Escobar³

Affiliations

¹ Institute of Biomedical Informatics, Graz University of Technology, Graz, Austria.
² Small Animal Clinic, University of Veterinary Medicine Hannover Foundation, Hannover, Germany.
³ Clinic for Hematology, Oncology and Palliative Care, Rostock University Medical Center, University of Rostock, Rostock, Germany.
⁴ Division of Bioinformatics, Department of Biology, Friedrich-Alexander-University, Erlangen, Germany.
⁵ Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, University of Rostock, Rostock, Germany.
⁶ UQVETS Small Animal Hospital, School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia.

Abstract

Targeted next-generation sequencing (NGS) enables the identification of genomic variants in cancer patients with high sensitivity at relatively low costs, and has thus opened the era to personalized human oncology. Veterinary medicine tends to adopt new technologies at a slower pace compared to human medicine due to lower funding, nonetheless it embraces technological advancements over time. Hence, it is reasonable to assume that targeted NGS will be incorporated into routine veterinary practice in the foreseeable future. Many animal diseases have well-researched human counterparts and hence, insights gained from the latter might, in principle, be harnessed to elucidate the former. Here, we present the TiHoCL targeted NGS panel as a proof of concept, exemplifying how functional genomics and network approaches can be effectively used to leverage the wealth of information available for human diseases in the development of targeted sequencing panels for veterinary medicine. Specifically, the TiHoCL targeted NGS panel is a molecular tool for characterizing and stratifying canine lymphoma (CL) patients designed based on human non-Hodgkin lymphoma (NHL) research outputs. While various single nucleotide polymorphisms (SNPs) have been associated with high risk of developing NHL, poor prognosis and resistance to treatment in NHL patients, little is known about the genetics of CL. Thus, the ~100 SNPs featured in the TiHoCL targeted NGS panel were selected using functional genomics and network approaches following a literature and database search that shielded ~500 SNPs associated with, in nearly all cases, human hematologic malignancies. The TiHoCL targeted NGS panel underwent technical validation and preliminary functional assessment by sequencing DNA samples isolated from blood of 29 lymphoma dogs using an Ion Torrent^™ PGM System achieving good sequencing run metrics. Our design framework holds new possibilities for the design of similar molecular tools applied to other diseases for which limited knowledge is available and will improve drug target discovery and patient care.

Keywords: canine lymphoma; comparative genomics; comparative oncology; genomic variants; network biology; patient stratification; personalized oncology; targeted next-generation sequencing.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by TU Graz Open Access Publishing Fund.