Machine learning-based automated phenotyping of inflammatory nocifensive behavior in mice

Wotton, Janine M.; Peterson, Emma; Anderson, Laura; Murray, Stephen A.; Braun, Robert E.; Chesler, Elissa J.; White, Jacqueline K.; Kumar, Vivek

doi:10.1177/1744806920958596

Cited by 16 publications

(23 citation statements)

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“…The discrepancy between these results could be explained by difference in timing of tissue collection, route of administration, and C57BL/6 substrain differences that could affect these results (52). Indeed, we and others recently reported that C57BL/6J and C57BL/6N substrains differ in their responses in acute and tonic pain models (53)(54)(55).…”

Section: Discussionmentioning

confidence: 88%

Impact of Dose, Sex, and Strain on Oxaliplatin-Induced Peripheral Neuropathy in Mice

et al. 2021

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Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose limiting, and long-lasting side effect of chemotherapy treatment. Unfortunately, no treatment has proven efficacious for this side effect. Rodent models play a crucial role in the discovery of new mechanisms underlying the initiation, progression, and recovery of CIPN and the potential discovery of new therapeutics. However, there is limited consistency in the dose, the sex, age, and genetic background of the animal used in these studies and the outcome measures used in evaluation of CIPN rely primarily on noxious and reflexive measures. The main objective of this study was to provide a comprehensive and systematic characterization of oxaliplatin-induced peripheral neuropathy in mice by using a battery of behavioral, sensory, electrophysiological, and morphometric measures in both sexes of the two widely used strains of mice, C57BL/6J and BALB/cJ. Mice received intraperitoneal injections of 3 or 30 mg/kg cumulative doses of oxaliplatin over the course of 2 weeks. Both doses induced long-term and time-dependent mechanical and cold hypersensitivity. Our results show that 30 mg/kg oxaliplatin reduced the locomotor activity in C57BL/6J mice, and C57BL/6J females showed anxiety-like behavior one-week post completion of treatment. In the same dose group, BALB/cJ males and females sustained a larger decrease in sucrose preference than either male or female C57BL/6J mice. Both strains failed to show significant changes in burrowing and nesting behaviors. Two clinically relevant assessments of changes to the peripheral nerve fibers, nerve conduction and intraepidermal nerve fiber density (IENFD) were evaluated. Only BALB/cJ females showed significant reduction in the nerve conduction amplitude 1 week after 30 mg/kg oxaliplatin regimen. Moreover, this dose of the chemo agent reduced the IENF density in both sexes and strains. Our findings suggest that mouse strain, sex, and assay type should be carefully considered when assessing the effects of oxaliplatin and potential therapeutic interventions.

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Section: Discussionmentioning

confidence: 88%

Impact of Dose, Sex, and Strain on Oxaliplatin-Induced Peripheral Neuropathy in Mice

et al. 2021

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“…org/ impre ss/ Pipel ineIn fo? id= 15; pain pilot study, Wotton et al 2020; https:// www. mouse pheno type.…”

Section: Discussionmentioning

confidence: 99%

“…respiration, inflammation), in some cases only in centre-specific pipelines or pilot studies (e.g. immunophenotyping, https://www.mousephenotype.org/impress/PipelineInfo?id=15 ; pain pilot study, Wotton et al 2020 ; https://www.mousephenotype.org/understand/data-collections/pain/ ). The goal of the IMPC is to ascribe altered physiological function in the presence of a null mutation, hence additional challenges are intentionally minimised to increase the signal of the mutated genotype.…”

Section: Discussionmentioning

confidence: 99%

Pleiotropy data resource as a primer for investigating co-morbidities/multi-morbidities and their role in disease

et al. 2021

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Most current biomedical and protein research focuses only on a small proportion of genes, which results in a lost opportunity to identify new gene-disease associations and explore new opportunities for therapeutic intervention. The International Mouse Phenotyping Consortium (IMPC) focuses on elucidating gene function at scale for poorly characterized and/or under-studied genes. A key component of the IMPC initiative is the implementation of a broad phenotyping pipeline, which is facilitating the discovery of pleiotropy. Characterizing pleiotropy is essential to identify gene-disease associations, and it is of particular importance when elucidating the genetic causes of syndromic disorders. Here we show how the IMPC is effectively uncovering pleiotropy and how the new mouse models and gene function hypotheses generated by the IMPC are increasing our understanding of the mammalian genome, forming the basis of new research and identifying new gene-disease associations.

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“…Advances in the Fourth-generation RNA-seq platforms, especially in situ sequencing (ISS) and fluorescent ISS (FISSEQ), have greatly helped to achieve the objectives and aims of RNA-seq techniques [ 69 , 74 ]. ISS technique is highly sensitive and involves the use of padlock probes and rolling circle amplification (RCA) to generate targeted sequencing libraries, which are later sequenced by the application of NGS techniques.…”

Section: Spatial Transcriptomicsmentioning

confidence: 99%

Single-Cell RNA Sequencing with Spatial Transcriptomics of Cancer Tissues

Ahmed

Zaman

Chowdhury

et al. 2022

IJMS

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Single-cell RNA sequencing (RNA-seq) techniques can perform analysis of transcriptome at the single-cell level and possess an unprecedented potential for exploring signatures involved in tumor development and progression. These techniques can perform sequence analysis of transcripts with a better resolution that could increase understanding of the cellular diversity found in the tumor microenvironment and how the cells interact with each other in complex heterogeneous cancerous tissues. Identifying the changes occurring in the genome and transcriptome in the spatial context is considered to increase knowledge of molecular factors fueling cancers. It may help develop better monitoring strategies and innovative approaches for cancer treatment. Recently, there has been a growing trend in the integration of RNA-seq techniques with contemporary omics technologies to study the tumor microenvironment. There has been a realization that this area of research has a huge scope of application in translational research. This review article presents an overview of various types of single-cell RNA-seq techniques used currently for analysis of cancer tissues, their pros and cons in bulk profiling of transcriptome, and recent advances in the techniques in exploring heterogeneity of various types of cancer tissues. Furthermore, we have highlighted the integration of single-cell RNA-seq techniques with other omics technologies for analysis of transcriptome in their spatial context, which is considered to revolutionize the understanding of tumor microenvironment.

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Machine learning-based automated phenotyping of inflammatory nocifensive behavior in mice

Cited by 16 publications

References 50 publications

Impact of Dose, Sex, and Strain on Oxaliplatin-Induced Peripheral Neuropathy in Mice

Impact of Dose, Sex, and Strain on Oxaliplatin-Induced Peripheral Neuropathy in Mice

Pleiotropy data resource as a primer for investigating co-morbidities/multi-morbidities and their role in disease

Single-Cell RNA Sequencing with Spatial Transcriptomics of Cancer Tissues

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