Human pathways in animal models: possibilities and limitations
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Human pathways in animal models : possibilities and limitations. / Doncheva, Nadezhda T.; Palasca, Oana; Yarani, Reza; Litman, Thomas; Anthon, Christian; Groenen, Martien A.M.; Stadler, Peter F.; Pociot, Flemming; Jensen, Lars J.; Gorodkin, Jan.
In: Nucleic Acids Research, Vol. 49, No. 4, 2021, p. 1859-1871.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Human pathways in animal models
T2 - possibilities and limitations
AU - Doncheva, Nadezhda T.
AU - Palasca, Oana
AU - Yarani, Reza
AU - Litman, Thomas
AU - Anthon, Christian
AU - Groenen, Martien A.M.
AU - Stadler, Peter F.
AU - Pociot, Flemming
AU - Jensen, Lars J.
AU - Gorodkin, Jan
PY - 2021
Y1 - 2021
N2 - Animal models are crucial for advancing our knowledge about the molecular pathways involved in human diseases. However, it remains unclear to what extent tissue expression of pathways in healthy individuals is conserved between species. In addition, organism-specific information on pathways in animal models is often lacking. Within these limitations, we explore the possibilities that arise from publicly available data for the animal models mouse, rat, and pig. We approximate the animal pathways activity by integrating the human counterparts of curated pathways with tissue expression data from the models. Specifically, we compare whether the animal orthologs of the human genes are expressed in the same tissue. This is complicated by the lower coverage and worse quality of data in rat and pig as compared to mouse. Despite that, from 203 human KEGG pathways and the seven tissues with best experimental coverage, we identify 95 distinct pathways, for which the tissue expression in one animal model agrees better with human than the others. Our systematic pathway-tissue comparison between human and three animal modes points to specific similarities with human and to distinct differences among the animal models, thereby suggesting the most suitable organism for modeling a human pathway or tissue.
AB - Animal models are crucial for advancing our knowledge about the molecular pathways involved in human diseases. However, it remains unclear to what extent tissue expression of pathways in healthy individuals is conserved between species. In addition, organism-specific information on pathways in animal models is often lacking. Within these limitations, we explore the possibilities that arise from publicly available data for the animal models mouse, rat, and pig. We approximate the animal pathways activity by integrating the human counterparts of curated pathways with tissue expression data from the models. Specifically, we compare whether the animal orthologs of the human genes are expressed in the same tissue. This is complicated by the lower coverage and worse quality of data in rat and pig as compared to mouse. Despite that, from 203 human KEGG pathways and the seven tissues with best experimental coverage, we identify 95 distinct pathways, for which the tissue expression in one animal model agrees better with human than the others. Our systematic pathway-tissue comparison between human and three animal modes points to specific similarities with human and to distinct differences among the animal models, thereby suggesting the most suitable organism for modeling a human pathway or tissue.
U2 - 10.1093/nar/gkab012
DO - 10.1093/nar/gkab012
M3 - Journal article
C2 - 33524155
AN - SCOPUS:85102395823
VL - 49
SP - 1859
EP - 1871
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 4
ER -
ID: 258895979