MicroRNA clusters integrate evolutionary constraints on expression and target affinities : the miR-6/5/4/286/3/309 cluster in Drosophila

This research was supported by the Hong Kong Research Grant Council GRF Grant (14103516), The Chinese University of Hong Kong Direct Grant (4053248), and TUYF Charitable Trust (6903957) (JHLH).A striking feature of microRNAs is that they are often clustered in the genomes of animals. The functional and evolutionary consequences of this clustering remain obscure. Here, we investigated a microRNA cluster miR-6/5/4/286/3/309 that is conserved across drosophilid lineages. Small RNA sequencing revealed expression of this microRNA cluster in Drosophila melanogaster leg discs, and conditional overexpression of the whole cluster resulted in leg appendage shortening. Transgenic overexpression lines expressing different combinations of microRNA cluster members were also constructed. Expression of individual microRNAs from the cluster resulted in a normal wild-type phenotype, but either the expression of several ancient microRNAs together (miR-5/4/286/3/309) or more recently evolved clustered microRNAs (miR-6-1/2/3) can recapitulate the phenotypes generated by the whole-cluster overexpression. Screening of transgenic fly lines revealed down-regulation of leg patterning gene cassettes in generation of the leg-shortening phenotype. Furthermore, cell transfection with different combinations of microRNA cluster members revealed a suite of downstream genes targeted by all cluster members, as well as complements of targets that are unique for distinct microRNAs. Considered together, the microRNA targets and the evolutionary ages of each microRNA in the cluster demonstrates the importance of microRNA clustering, where new members can reinforce and modify the selection forces on both the cluster regulation and the gene regulatory network of existing microRNAs.PostprintPeer reviewe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained

Erratum:Micro-RNA Clusters Integrate Evolutionary Constraints on Expression and Target Affinities: The miR-6/5/4/286/3/309 Cluster in Drosophila (Molecular Biology and Evolution (2020) 37:10 (2955–2965) DOI: 10.1093/molbev/msaa146)

This is a correction to: Qu Zhe, Wing Chung Yiu, Ho Yin Yip, Wenyan Nong, Clare W C Yu, Ivy H T Lee, Annette Y P Wong, Nicola W Y Wong, Fiona K M Cheung, Ting Fung Chan, Kwok Fai Lau, Silin Zhong, Ka Hou Chu, Stephen S Tobe, David E K Ferrier, William G Bendena, Jerome H L Hui, Micro-RNA Clusters Integrate Evolutionary Constraints on Expression and Target Affinities: The miR-6/5/4/286/3/309 Cluster in Drosophila, Molecular Biology and Evolution, Volume 37, Issue 10, October 2020, Pages 2955–2965, https://doi.org/10.1093/molbev/msaa146 Upon original publication, the term ‘microRNA’ was incorrectly given as ‘micro-RNA’ in the title, Key words and throughout the main body of the paper. In addition, the name and surname of author Zhe Qu were inadvertently transposed. These details have been corrected only in this correction notice to preserve the published version of record.</p

Erratum:Micro-RNA Clusters Integrate Evolutionary Constraints on Expression and Target Affinities: The miR-6/5/4/286/3/309 Cluster in Drosophila (Molecular Biology and Evolution (2020) 37:10 (2955–2965) DOI: 10.1093/molbev/msaa146)

This is a correction to: Qu Zhe, Wing Chung Yiu, Ho Yin Yip, Wenyan Nong, Clare W C Yu, Ivy H T Lee, Annette Y P Wong, Nicola W Y Wong, Fiona K M Cheung, Ting Fung Chan, Kwok Fai Lau, Silin Zhong, Ka Hou Chu, Stephen S Tobe, David E K Ferrier, William G Bendena, Jerome H L Hui, Micro-RNA Clusters Integrate Evolutionary Constraints on Expression and Target Affinities: The miR-6/5/4/286/3/309 Cluster in Drosophila, Molecular Biology and Evolution, Volume 37, Issue 10, October 2020, Pages 2955–2965, https://doi.org/10.1093/molbev/msaa146 Upon original publication, the term ‘microRNA’ was incorrectly given as ‘micro-RNA’ in the title, Key words and throughout the main body of the paper. In addition, the name and surname of author Zhe Qu were inadvertently transposed. These details have been corrected only in this correction notice to preserve the published version of record.</p

Search for the Decays B-D(0)-]Gamma-Gamma and B-S(0)-]Gamma-Gamma

Contains fulltext : 26235.pdf (publisher's version ) (Open Access

Observation of multiple hard photon final states at root s=130-140 GeV at LEP

Contains fulltext : 28593.pdf (preprint version ) (Open Access

Search for excited leptons in e+^+e−^- annihilation at s\sqrt{s} = 130-140 GeV

We report on a search for the excited leptons e^*,mu^*,tau^* and nu^* in e+e- collisions at sqrt{s} = 130 - 140 GeV using the L3 detector at LEP. No evidence has been found for their existence. From an analysis of the expected pair produced l^*l^* in the channels e.e.gamma.gamma, mu.mu.gamma.gamma, tau.tau.gamma.gamma, eeWW, and nu.nu.gamma.gamma, we determine the lower mass limits at 95% C.L. of 64.7 GeV for e^*, 64.9 GeV for mu^*, 64.2 GeV for tau*, 57.3 GeV ( eW decay mode) and 61.4 GeV ( nu.gamma decay mode) for nu^*. From an analysis of the expected singly produced l.l^* in the channels e.e.gamma, mu.mu.gamma, tau.tau.gamma, nu.eW and nu.nu.gamma, we determine upper limits on the couplings lambda/m_{l^*} up to m_{l^*} = 130 Ge