Preclinical Species Gene Expression Database: Development and Meta-Analysis
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ABSTRACT:
ORGANISM(S): Rattus norvegicus Mus musculus Canis lupus familiaris Macaca fascicularis
PROVIDER: GSE219045 | GEO | 2022/12/12
REPOSITORIES: GEO
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Project description:Preclinical Species Gene Expression Database: Development and Meta-Analysis
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Project description:Early attrition of drug candidates, including kinase inhibitors, often occurs due to issues that arise during preclinical safety and efficacy evaluation. This problem may be exacerbated by the fact that these studies might fail to consider the basic physiological differences which could exist between human patients and animal models. Little is currently known about how kinase expression can vary between species, and tools to quantitatively measure such differences are lacking. We report the development of a targeted mass spectrometry-based assay capable of monitoring >50 different kinases using peptides conserved in humans and the key preclinical species used in drug development (mouse, rat, dog and cynomolgus monkey). These methods were then used to profile inter-species kinome variability in spleen with three of the current techniques used in targeted proteomics (MRM, PRM and IS-PRM). IS-PRM provided the highest number of kinase identifications, and the results indicate that while this initial set of kinases exhibits high correlation between species for this tissue type, discreet species-specific differences do exist, especially within the cyclin-dependent kinase (CDK) family. Understanding these differences could help rationalize the findings of preclinical studies and have major implications for the selection of these animals as models in kinase drug development.
2021-08-19 | PXD024650 | panorama
Project description:Sensory neurons of the dorsal root ganglion (DRG) play a crucial role in maintaining tissue homeostasis by sensing and initiating responses to stimuli. While most preclinical studies of DRGs are conducted in rodents, much less is known about the mechanisms of sensory perception in primates. We generated a transcriptome atlas for mouse, guinea pig, cynomolgus monkey, and human DRGs using a framework that implements a common laboratory workflow (i.e sequencing technologies, laboratory protocols, and sample archival methods) and multiple data-integration approaches to generate accurate cross-species mappings of sensory neuron subtypes.
2022-12-21 | GSE201653 | GEO
Project description:Sensory neurons of the dorsal root ganglion (DRG) play a crucial role in maintaining tissue homeostasis by sensing and initiating responses to stimuli. While most preclinical studies of DRGs are conducted in rodents, much less is known about the mechanisms of sensory perception in primates. We generated a transcriptome atlas for mouse, guinea pig, cynomolgus monkey, and human DRGs using a framework that implements a common laboratory workflow (i.e sequencing technologies, laboratory protocols, and sample archival methods) and multiple data-integration approaches to generate accurate cross-species mappings of sensory neuron subtypes.
2022-12-21 | GSE201586 | GEO
Project description:Sensory neurons of the dorsal root ganglion (DRG) play a crucial role in maintaining tissue homeostasis by sensing and initiating responses to stimuli. While most preclinical studies of DRGs are conducted in rodents, much less is known about the mechanisms of sensory perception in primates. We generated a transcriptome atlas for mouse, guinea pig, cynomolgus monkey, and human DRGs using a framework that implements a common laboratory workflow (i.e sequencing technologies, laboratory protocols, and sample archival methods) and multiple data-integration approaches to generate accurate cross-species mappings of sensory neuron subtypes.
2022-12-21 | GSE201585 | GEO
Project description:Sensory neurons of the dorsal root ganglion (DRG) play a crucial role in maintaining tissue homeostasis by sensing and initiating responses to stimuli. While most preclinical studies of DRGs are conducted in rodents, much less is known about the mechanisms of sensory perception in primates. We generated a transcriptome atlas for mouse, guinea pig, cynomolgus monkey, and human DRGs using a framework that implements a common laboratory workflow (i.e sequencing technologies, laboratory protocols, and sample archival methods) and multiple data-integration approaches to generate accurate cross-species mappings of sensory neuron subtypes.
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Project description:Objective: To investigate peripheral blood cell (PBCs) global gene expression profile of SSc at its preclinical stage (PreSSc) and to characterize the molecular changes associated with progression to a definite disease over time. Material and methods: Clinical data and PBCs of 33 participants with PreSSc and 16 healthy controls (HCs) were collected at baseline and follow-up (mean 4.2 years). Global gene expression profiling was conducted by RNA sequencing and a modular analysis was performed. Results: Comparison of baseline PreSSc to HCs revealed 2889 differentially expressed genes. Interferon signalling was the only activated pathway among top over-represented pathways. Moreover, 10 modules were significantly decreased in PreSSc samples (related to lymphoid lineage, cytotoxic/NK cell, and erythropoiesis) in comparison to HCs. At follow-up, 14 subjects (42.4%) presented signs of progression (evolving PreSSc) and 19 remained in stable preclinical stage (stable PreSSc). Progression was not associated with baseline clinical features or baseline PBC transcript modules. At follow-up stable PreSSc normalized their down-regulated cytotoxic/NK cell and protein synthesis modules while evolving PreSSc kept a down-regulation of cytotoxic/NK cell and protein synthesis modules. Transcript level changes of follow-up vs baseline in stable PreSSc vs evolving PreSSc showed 549 differentially expressed transcripts (336 up and 213 down) with upregulation of the EIF2 Signalling pathway. Conclusions: Participants with PreSSc had a distinct gene expression profile indicating that molecular differences at a transcriptomic level are al_x0002_ready present in the preclinical stages of SSc. Furthermore, a reduced NK signature in PBCs was related to SSc progression over time.
2023-09-13 | GSE224849 | GEO
Project description:Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, non-invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a “standard of care” chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents. A total of 17 samples are provided reprsenting TH-MYCN tumors derived from mice
2011-03-17 | E-GEOD-27516 | biostudies-arrayexpress
Project description:Most preclinical models of IBD were developed in mice which share 85% genomic homology with humans and are genetically tractable. However, rats have historically been the model of choice for immunologic, cardiovascular, and neurologic diseases because they more closely recapitulate human physiology6. Recent work on the role of microbial dysbiosis in IBD has also shown that rat microbiota is more closely related to those of humans than mice7. Taken together, this suggests that a single preclinical model may not be optimal for delineating the molecular pathways involved in IBD pathogenesis. Previous research in rat models of IBD have focused primarily on characterization of clinical score and histopathological findings8, with a lack of systematic investigation into potential molecular pathways affected, thereby making it difficult to integrate this model with other preclinical and clinical research. In the current study, we have undertaken a systematic transcriptomic analysis of a rat model of experimental colitis along with a three-way comparison between an established mouse preclinical model and available human clinical datasets in an effort to identify conserved immunological pathways in IBD.
2023-11-06 | GSE245994 | GEO
Project description:To study the features of tumor microenvironment (TME) of BM brain metastasis, a proteomic approach has been performed in a preclinical BM model with the human lung adenocarcinoma-derived H2030-BrM3 cells implanted into the cortex and striatum of nude rats. Proteomic analyzes were performed 24 days after tumor cell inoculation. Here, we provided protein expression changes in BM compared to healthy brain tissue with rat analyzes. In total, 8420 proteins were quantified from the 8 samples analyzed.
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