scholarly journals PopTargs: a database for studying population evolutionary genetics of human microRNA target sites

Database ◽  
2019 ◽  
Vol 2019 ◽  
Author(s):  
Andrea Hatlen ◽  
Mohab Helmy ◽  
Antonio Marco

Abstract There is an increasing interest in the study of polymorphic variants at gene regulatory motifs, including microRNA target sites. Understanding the effects of selective forces at specific microRNA target sites, together with other factors like expression levels or evolutionary conservation, requires the joint study of multiple datasets. We have compiled information from multiple sources and compared it with predicted microRNA target sites to build a comprehensive database for the study of microRNA targets in human populations. PopTargs is a web-based tool that allows the easy extraction of multiple datasets and the joint analyses of them, including allele frequencies, ancestral status, population differentiation statistics and site conservation. The user can also compare the allele frequency spectrum between two groups of target sites and conveniently produce plots. The database can be easily expanded as new data becomes available and the raw database as well as code for creating new custom-made databases is available for downloading. We also describe a few illustrative examples.

2019 ◽  
Author(s):  
Andrea Hatlen ◽  
Mohab Helmy ◽  
Antonio Marco

ABSTRACTThere is an increasing interest in the study of polymorphic variants at gene regulatory motifs, including microRNA target sites. Understanding the effects of selective forces at specific microRNA target sites, together with other factors like expression levels or evolutionary conservation, requires the joint study of multiple datasets. We have compiled information from multiple sources and compare it with predicted microRNA target sites to built a comprehensive database for the study of microRNA targets in human populations. PopTargs is a web-based tool that allows the easy extraction of multiple datasets and the joint analyses of them, including allele frequencies, ancestral status, population differentiation statistics and site conservation. The user can also compare the allele frequency spectrum between two groups of target sites, and conveniently produce plots. The database can be easily expanded as new data becomes available and the raw database as well as code for creating new custom made databases are available for downloading. We also describe a few illustrative examples.Availability and implementationPoptargs is available at http://[email protected]


2018 ◽  
Author(s):  
Andrea Hatlen ◽  
Antonio Marco

ABSTRACTMicroRNA target sites are often conserved during evolution and purifying selection to maintain such sites is expected. On the other hand, comparative analyses identified a paucity of microRNA target sites in co-expressed transcripts, and novel target sites can potentially be deleterious. We proposed that selection against novel target sites pervasive. The analysis of derived allele frequencies revealed that, when the derived allele is a target site, the proportion of non-target sites is higher than expected, particularly for highly expressed microRNAs. Thus, new alleles generating novel microRNA target sites can be deleterious and selected against. When we analysed ancestral target sites the derived (non-target) allele frequency does not show statistical support for microRNA target allele conservation. We investigated the joint effects of microRNA conservation and expression and found that selection against microRNA target sites depends mostly on the expression level of the microRNA. We identified microRNA target sites with relatively high levels of population differentiation. However, when we analyse separately target sites in which the target allele is ancestral to the population, the proportion of SNPs with high Fst significantly increases. These findings support population differentiation is more likely in target sites that are lost than in the gain of new target sites. Our results indicate that selection against novel microRNA target sites is prevalent and, although individual sites may have a weak selective pressure, the overall effect across untranslated regions is not negligible and should be accounted when studying the evolution of genomic sequences.


2020 ◽  
Vol 37 (12) ◽  
pp. 3399-3408
Author(s):  
Andrea Hatlen ◽  
Antonio Marco

Abstract MicroRNA target sites are often conserved during evolution and purifying selection to maintain such sites is expected. On the other hand, comparative analyses identified a paucity of microRNA target sites in coexpressed transcripts, and novel target sites can potentially be deleterious. We proposed that selection against novel target sites pervasive. The analysis of derived allele frequencies revealed that, when the derived allele is a target site, the proportion of nontarget sites is higher than expected, particularly for highly expressed microRNAs. Thus, new alleles generating novel microRNA target sites can be deleterious and selected against. When we analyzed ancestral target sites, the derived (nontarget) allele frequency does not show statistical support for microRNA target allele conservation. We investigated the joint effects of microRNA conservation and expression and found that selection against microRNA target sites depends mostly on the expression level of the microRNA. We identified microRNA target sites with relatively high levels of population differentiation. However, when we analyze separately target sites in which the target allele is ancestral to the population, the proportion of single-nucleotide polymorphisms with high Fst significantly increases. These findings support that population differentiation is more likely in target sites that are lost than in the gain of new target sites. Our results indicate that selection against novel microRNA target sites is prevalent and, although individual sites may have a weak selective pressure, the overall effect across untranslated regions is not negligible and should be accounted when studying the evolution of genomic sequences.


BMC Nursing ◽  
2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Tanja Gustafsson ◽  
Annelie J Sundler ◽  
Elisabeth Lindberg ◽  
Pernilla Karlsson ◽  
Hanna Maurin Söderholm

Abstract Background There is currently a strong emphasis on person-centred care (PCC) and communication; however, little research has been conducted on how to implement person-centred communication in home care settings. Therefore, the ACTION (A person-centred CommunicaTION) programme, which is a web-based education programme focusing on person-centred communication developed for nurse assistants (NAs) providing home care for older persons, was implemented. This paper reports on the process evaluation conducted with the aim to describe and evaluate the implementation of the ACTION programme. Methods A descriptive design with a mixed method approach was used. Twenty-seven NAs from two units in Sweden were recruited, and 23 of them were offered the educational intervention. Quantitative and qualitative data were collected from multiple sources before, during and after the implementation. Quantitative data were used to analyse demographics, attendance and participation, while qualitative data were used to evaluate experiences of the implementation and contextual factors influencing the implementation. Results The evaluation showed a high degree of NA participation in the first five education modules, and a decrease in the three remaining modules. Overall, the NAs perceived the web format to be easy to use and appreciated the flexibility and accessibility. The content was described as important. Challenges included time constraints; the heavy workload; and a lack of interaction, space and equipment to complete the programme. Conclusions The results suggest that web-based education seems to be an appropriate strategy in home care settings; however, areas for improvement were identified. Our findings show that participants appreciated the web-based learning format in terms of accessibility and flexibility, as well as the face-to-face group discussions. The critical importance of organizational support and available resources are highlighted, such as management involvement and local facilitation. In addition, the findings report on the implementation challenges specific to the dynamic home care context. Trial registration This intervention was implemented with nursing assistants, and the evaluation only involved nursing staff. Patients were not part of this study. According to the ICMJE, registration was not necessary ().


2015 ◽  
Vol 89 (12) ◽  
pp. 6167-6170 ◽  
Author(s):  
Jessica K. Fiege ◽  
Ryan A. Langlois

Influenza A viruses display a broad cellular tropism within the respiratory tracts of mammalian hosts. Uncovering the relationship between tropism and virus immunity, pathogenesis, and transmission will be critical for the development of therapeutic interventions. Here we discuss recent developments of several recombinant strains of influenza A virus. These viruses have inserted reporters to track tropism, microRNA target sites to restrict tropism, or barcodes to assess transmission dynamics, expanding our understanding of pathogen-host interactions.


2006 ◽  
Vol 174 (5) ◽  
pp. 677-687 ◽  
Author(s):  
Hak Kyun Kim ◽  
Yong Sun Lee ◽  
Umasundari Sivaprasad ◽  
Ankit Malhotra ◽  
Anindya Dutta

Three muscle-specific microRNAs, miR-206, -1, and -133, are induced during differentiation of C2C12 myoblasts in vitro. Transfection of miR-206 promotes differentiation despite the presence of serum, whereas inhibition of the microRNA by antisense oligonucleotide inhibits cell cycle withdrawal and differentiation, which are normally induced by serum deprivation. Among the many mRNAs that are down-regulated by miR-206, the p180 subunit of DNA polymerase α and three other genes are shown to be direct targets. Down-regulation of the polymerase inhibits DNA synthesis, an important component of the differentiation program. The direct targets are decreased by mRNA cleavage that is dependent on predicted microRNA target sites. Unlike small interfering RNA–directed cleavage, however, the 5′ ends of the cleavage fragments are distributed and not confined to the target sites, suggesting involvement of exonucleases in the degradation process. In addition, inhibitors of myogenic transcription factors, Id1-3 and MyoR, are decreased upon miR-206 introduction, suggesting the presence of additional mechanisms by which microRNAs enforce the differentiation program.


2015 ◽  
pp. btv537 ◽  
Author(s):  
Jeongbin Park ◽  
Sangsu Bae ◽  
Jin-Soo Kim
Keyword(s):  

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