Dataset Information

Automated Hypothesis Generation to Identify Signals Relevant in the Development of Mammalian Cell and Tissue Bioprocesses, With Validation in a Retinal Culture System.

ABSTRACT: We have developed an accessible software tool (receptoR) to predict potentially active signaling pathways in one or more cell type(s) of interest from publicly available transcriptome data. As proof-of-concept, we applied it to mouse photoreceptors, yielding the previously untested hypothesis that activin signaling pathways are active in these cells. Expression of the type 2 activin receptor (Acvr2a) was experimentally confirmed by both RT-qPCR and immunochemistry, and activation of this signaling pathway with recombinant activin A significantly enhanced the survival of magnetically sorted photoreceptors in culture. Taken together, we demonstrate that our approach can be easily used to mine publicly available transcriptome data and generate hypotheses around receptor expression that can be used to identify novel signaling pathways in specific cell types of interest. We anticipate that receptoR (available at https://www.ucalgary.ca/ungrinlab/receptoR) will enable more efficient use of limited research resources.

SUBMITTER: Toms D

PROVIDER: S-EPMC7287043 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Automated Hypothesis Generation to Identify Signals Relevant in the Development of Mammalian Cell and Tissue Bioprocesses, With Validation in a Retinal Culture System.

Toms Derek D Al-Ani Abdullah A Sunba Saud S Tong Qing Yun Victor QYV Workentine Matthew M Ungrin Mark M

Frontiers in bioengineering and biotechnology 20200604

We have developed an accessible software tool (receptoR) to predict potentially active signaling pathways in one or more cell type(s) of interest from publicly available transcriptome data. As proof-of-concept, we applied it to mouse photoreceptors, yielding the previously untested hypothesis that activin signaling pathways are active in these cells. Expression of the type 2 activin receptor (<i>Acvr2a</i>) was experimentally confirmed by both RT-qPCR and immunochemistry, and activation of this ...[more]

PMID: 32582664

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Project description:BackgroundProduct risk management involves critical assessment of the risks and benefits of health products circulating in the market. One of the important sources of safety information is the primary literature, especially for newer products which regulatory authorities have relatively little experience with. Although the primary literature provides vast and diverse information, only a small proportion of which is useful for product risk assessment work. Hence, the aim of this study is to explore the possibility of using text mining to automate the identification of useful articles, which will reduce the time taken for literature search and hence improving work efficiency. In this study, term-frequency inverse document-frequency values were computed for predictors extracted from the titles and abstracts of articles related to three tumour necrosis factors-alpha blockers. A general automated system was developed using only general predictors and was tested for its generalizability using articles related to four other drug classes. Several specific automated systems were developed using both general and specific predictors and training sets of different sizes in order to determine the minimum number of articles required for developing such systems.ResultsThe general automated system had an area under the curve value of 0.731 and was able to rank 34.6% and 46.2% of the total number of 'useful' articles among the first 10% and 20% of the articles presented to the evaluators when tested on the generalizability set. However, its use may be limited by the subjective definition of useful articles. For the specific automated system, it was found that only 20 articles were required to develop a specific automated system with a prediction performance (AUC 0.748) that was better than that of general automated system.ConclusionsSpecific automated systems can be developed rapidly and avoid problems caused by subjective definition of useful articles. Thus the efficiency of product risk management can be improved with the use of specific automated systems.

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Project description:Tactile stimuli on moving limbs are typically attenuated during reach planning and execution. This phenomenon has been related to internal forward models that predict the sensory consequences of a movement. Tactile suppression is considered to occur due to a match between the actual and predicted sensory consequences of a movement, which might free capacities to process novel or task-relevant sensory signals. Here, we examined whether and how tactile suppression depends on the relevance of somatosensory information for reaching. Participants reached with their left or right index finger to the unseen index finger of their other hand (body target) or an unseen pad on a screen (external target). In the body target condition, somatosensory signals from the static hand were available for localizing the reach target. Vibrotactile stimuli were presented on the moving index finger before or during reaching or in a separate no-movement baseline block, and participants indicated whether they detected a stimulus. As expected, detection thresholds before or during reaching were higher compared with baseline. Tactile suppression was also stronger for reaches to body targets than external targets, as reflected by higher detection thresholds and lower precision of detectability. Moreover, detection thresholds were higher when reaching with the left than with the right hand. Our results suggest that tactile suppression is modulated by position signals from the target limb that are required to reach successfully to the own body. Moreover, limb dominance seems to affect tactile suppression, presumably due to disparate uncertainty of feedback signals from the moving limb.NEW & NOTEWORTHY Tactile suppression on a moving limb has been suggested to release computational resources for processing other relevant sensory events. In the current study, we show that tactile sensitivity on the moving limb decreases more when reaching to body targets than external targets. This indicates that tactile perception can be modulated by allocating processing capacities to movement-relevant somatosensory information at the target location. Our results contribute to understanding tactile processing and predictive mechanisms in the brain.

Dataset Information

Automated Hypothesis Generation to Identify Signals Relevant in the Development of Mammalian Cell and Tissue Bioprocesses, With Validation in a Retinal Culture System.

Publications

Automated Hypothesis Generation to Identify Signals Relevant in the Development of Mammalian Cell and Tissue Bioprocesses, With Validation in a Retinal Culture System.

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