Author：Zha, L;Shen, J;Tefsen, B;Wang, YJ;Lu, WH;Xu, QC

Author：Lee, MH;Jiang, BJ;Tsigkou, A

Author：Archary, D;Rong, R;Gordon, ML;Boliar, S;Gray, ES;Dugast, A;Hermanus, T;Goulder, PJ;Coovadia, HM;Morris, L;Alter, G;Derdeyn, CA;Ndung'u, T

Author：Zhang, Bai-Ling ; Han, Guoxia

Abstract:Subcellular localization is a key functional characteristic of proteins. An automatic, reliable and efficient prediction system for protein subcellular localization can be used for establishing knowledge of the spatial distribution of proteins within living cells and permits to screen systems for drug discovery or for early diagnosis of a disease. In this paper, we investigate an approach based on augmented image features by incorporating curvelet transform and neural network (MLP) ensemble for classification. A simple Random Subspace (RS) ensemble offers satisfactory performance, which contains a set of base MLP classifiers trained with subsets of attributes randomly drawn from the combined features of curvelet coefficients and original Subcellular Location Features (SLF). An MLP ensemble with Random Linear Oracle (RLO) can further improve the performance by replacing a base classifier with a "miniensemble", which consists of a pair of base classifiers and a fixed, randomly created oracle that selects between them. With the benchmarking 2D HeLa images, our experiments show the effectiveness of the proposed approach. The RS-MLP ensemble offers the classification rate 95%% while the RS-RLO ensemble gives 95.7%% accuracy, which compares sharply with the previously published benchmarking result 84%%. © 2011 IEEE.

Author：Song, YY;Xu, QR;Wei, Z;Zhen, D;Su, JL;Chen, KQ;Meng, J

Abstract:Currently, although many successful bioinformatics efforts have been reported in the epitranscriptomics field for N-6-methyladenosine (m(6)A) site identification, none is focused on the substrate specificity of different m(6)A-related enzymes, ie, the methyltransferases (writers) and demethylases (erasers). In this work, to untangle the target specificity and the regulatory functions of different RNA m6A writers (METTL3-METT14 and METTL16) and erasers (ALKBH5 and FTO), we extracted 49 genomic features along with the conventional sequence features and used the machine learning approach of random forest to predict their epitranscriptome substrates. Our method achieved reasonable performance on both the writer target prediction (as high as 0.918) and the eraser target prediction (as high as 0.888) in a 5-fold crossvalidation, and results of the gene ontology analysis of their preferential targets further revealed the functional relevance of different RNA methylation writers and erasers.

Author：Nash, HC;Wirdateti;Low, GW;Choo, SW;Chong, JL;Semiadi, G;Hari, R;Sulaiman, MH;Turvey, ST;Evans, TA;Rheindt, FE

Abstract:The use of genome-wide genetic markers is an emerging approach for informing evidence-based management decisions for highly threatened species. Pangolins are the most heavily trafficked mammals across illegal wildlife trade globally, but critically endangered Sunda pangolins (Manis javanica) have not been widely studied in insular Southeast Asia. We used > 12,000 single nucleotide polymorphic markers (SNPs) to assign pangolin seizures from illegal trade of unknown origin to possible geographic sources via genetic clustering with pangolins of known origin. Our SNPs reveal three previously unrecognized genetic lineages of Sunda pangolins, possibly from Borneo, Java and Singapore/Sumatra. The seizure assignments suggest the majority of pangolins were traded from Borneo to Java. Using mitochondrial markers did not provide the same resolution of pangolin lineages, and to explore if admixture might explain these differences, we applied sophisticated tests of introgression using > 2000 SNPs to investigate secondary gene flow between each of the three Sunda pangolin lineages. It is possible the admixture which we discovered is due to human-mediated movements of pangolins. Our findings impact a range of conservation actions, including tracing patterns of trade, repatriation of rescue animals, and conservation breeding. In order to conserve genetic diversity, we suggest that, pending further research, each pangolin lineage should as a precaution be protected and managed as an evolutionarily distinct conservation unit.

Author：Ma, DQ;Bu, F;Jiang, LW;Quinn, JP;Wang, MY

Author：Peng, GD;Kashio, M;Morimoto, T;Li, TB;Zhu, JT;Tominaga, M;Kadowaki, T

Abstract:We have identified and characterized the TRPA1 channel of Varroa destructor (VdTRPA1), a major ectoparasitic mite of honey bee. One of the two VdTRPA1 isoforms, VdTRPA1L, was activated by a variety of plant-derived compounds, including electrophilic compounds, suggesting that chemical activation profiles are mostly shared between arthropod TRPA1 channels. Nevertheless, carvacrol and alpha-terpineol activated VdTRPA1L but not a honey bee noxious-stimuli-sensitive TRPA, AmHsTRPA, and Drosophila melanogaster TRPA1. Activation of VdTRPA1L in D. melanogaster taste neurons by the above compounds was sufficient to modify the gustatory behaviors. Carvacrol and a-terpineol repelled V. destructor in a laboratory assay, and a-terpineol repressed V. destructor entry for reproduction into the brood cells in hives. Understanding the functions of parasite TRP channels not only gives clues about the evolving molecular and cellular mechanisms of parasitism but also helps in the development of control methods.

Author：Wei, Z;Panneerdoss, S;Timilsina, S;Zhu, JT;Mohammad, TA;Lu, ZL;de Magalhaes, JP;Chen, YD;Rong, R;Huang, YF;Rao, MK;Meng, J

Abstract:Background. Compared with the well-studied 5-methylcytosine (m(5)C) in DNA, the role and topology of epitranscriptome m(5)C remain insufficiently characterized. Results. Through analyzing transcriptome-wide m(5)C distribution in human and mouse, we show that the m(5)C modification is significantly enriched at 5' untranslated regions (5' UTRs) of mRNA in human and mouse. With a comparative analysis of the mRNA and DNA methylome, we demonstrate that, like DNA methylation, transcriptome m(5)C methylation exhibits a strong clustering effect. Surprisingly, an inverse correlation between mRNA and DNA m(5)C methylation is observed at CpG sites. Further analysis reveals that RNA m(5)C methylation level is positively correlated with both RNA expression and RNA half-life. We also observed that the methylation level of mitochondrial RNAs is significantly higher than RNAs transcribed from the nuclear genome. Conclusions. This study provides an in-depth topological characterization of transcriptome-wide m(5)C modification by associating RNA m(5)C methylation patterns with transcriptional expression, DNA methylations, RNA stabilities, and mitochondrial genome.

Author：Park, J;Tefsen, B;Heemskerk, MJ;Lagendijk, EL;van den Hondel, CAMJJ;van Die, I;Ram, AFJ

Abstract:Background: Galactofuranose (Galf)-containing glycoconjugates are present in numerous microbes, including filamentous fungi where they are important for morphology, virulence and maintaining cell wall integrity. The incorporation of Galf-residues into galactomannan, galactomannoproteins and glycolipids is carried out by Golgi-localized Galf transferases. The nucleotide sugar donor used by these transferases (UDP-Galf) is produced in the cytoplasm and has to be transported to the lumen of the Golgi by a dedicated nucleotide sugar transporter. Methods: Based on homology with recently identified UDP-Galf-transporters in A. fumigatus and A. nidulans, two putative UDP-Galf-transporters in A. niger were found. Their function and localization was determined by gene deletions and GFP-tagging studies, respectively. Results: The two putative UDP-Galf-transporters in A. niger are homologous to each other and are predicted to contain eleven transmembrane domains (UgtA) or ten transmembrane domains (UgtB) due to a reduced length of the C-terminal part of the UgtB protein. The presence of two putative UDP-Galf-transporters in the genome was not unique for A. niger. From the twenty Aspergillus species analysed, nine species contained two additional putative UDP-Galf-transporters. Three of the nine species were outside the Aspergillus section nigri, indication an early duplication of UDP-Galf-transporters and subsequent loss of the UgtB copy in several aspergilli. Deletion analysis of the single and double mutants in A. niger indicated that the two putative UDP-Galf-transporters (named UgtA and UgtB) have a redundant function in UDP-Galf-transport as only the double mutant displayed a Galf-negative phenotype. The Galf-negative phenotype of the double mutant could be complemented by expressing either CFP-UgtA or CFP-UgtB fusion proteins from their endogenous promoters, indicating that both CFP-tagged proteins are functional. Both Ugt proteins co-localize with each other as well as with the GDP-mannose nucleotide transporter, as was demonstrated by fluorescence microscopy, thereby confirming their predicted localization in the Golgi. Conclusion: A. niger contains two genes encoding UDP-Galf-transporters. Deletion and localization studies indicate that UgtA and UgtB have redundant functions in the biosynthesis of Galf-containing glycoconjugates.

Author：Morimoto, T;Kojima, Y;Yoshiyama, M;Kimura, K;Yang, B;Kadowaki, T

Abstract:Chronic bee paralysis virus (CBPV) infection causes chronic paralysis and loss of workers in honey bee colonies around the world. Although CBPV shows a worldwide distribution, it had not been molecularly detected in Japan. Our investigation of Apis mellifera and Apis cerana japonica colonies with RT-PCR has revealed CBPV infection in A. mellifera but not A. c. japonica colonies in Japan. The prevalence of CBPV is low compared with that of other viruses: deformed wing virus (DWV), black queen cell virus (BQCV), Israel acute paralysis virus (IAPV), and sac brood virus (SBV), previously reported in Japan. Because of its low prevalence (5.6%%) in A. mellifera colonies, the incidence of colony losses by CBPV infection must be sporadic in Japan. The presence of the (-) strand RNA in dying workers suggests that CBPV infection and replication may contribute to their symptoms. Phylogenetic analysis demonstrates a geographic separation of Japanese isolates from European, Uruguayan, and mainland US isolates. The lack of major exchange of honey bees between Europe/mainland US and Japan for the recent 26 years (1985-2010) may have resulted in the geographic separation of Japanese CBPV isolates.

Author：Li Junwei;Wang Junhua;Kang Angray S;Sacitharan Pradeep Kumar

Abstract:A recent article by Grifoni et al. elegantly demonstrated the ability to measure and understand the human CD4+ and CD8+ T cell responses to SARS-CoV-2 infection. These findings highlighted below gave new insights into the immunopathogenesis of COVID-19, the crossreactivity of the SARS-CoV-2 infections, the potential targets of T cells, and for vaccine design.

Author：Ma, ZF;Zhang, HX;Teh, SS;Wang, CW;Zhang, YT;Hayford, F;Wang, LY;Ma, T;Dong, ZH;Zhang, Y;Zhu, YF

Abstract:Goji berries (Lycium fruits) are usually found in Asia, particularly in northwest regions of China. Traditionally, dried goji berries are cooked before they are consumed. They are commonly used in Chinese soups and as herbal tea. Moreover, goji berries are used for the production of tincture, wine, and juice. Goji berries are high antioxidant potential fruits which alleviate oxidative stress to confer many health protective benefits such as preventing free radicals from damaging DNA, lipids, and proteins. Therefore, the aim of the review was to focus on the bioactive compounds and pharmacological properties of goji berries including their molecular mechanisms of action. The health benefits of goji berries include enhancing hemopoiesis, antiradiation, antiaging, anticancer, improvement of immunity, and antioxidation. There is a better protection through synergistic and additive effects in fruits and herbal products from a complex mixture of phytochemicals when compared to one single phytochemical.

Author：Dong, XF;Chaisiri, K;Donnelly, MJ;McGarry, JW;Kadowaki, T;Darby, AC;Makepeace, BL

Author：Wee, WY;Dutta, A;Choo, SW

Abstract:Mycobacteria a genus of Actinobacteria are widespread in nature ranging from soil-dwelling saprophytes to human and animal pathogens. The rate of growth has been a classifying factor for the Mycobacterium spp., dividing them into the rapid growers and the slow growers. Here we have performed a comparative genome study of mycobacterial species in order to get better understanding of their evolution, particularly to understand the distinction between the rapid and slow growers. Our study shows that the slow growers had generally gained and lost more genes compared to the rapid growers. The slow growers might haved eventually lost genes (LivFGMH operon, shaACDEFG genes and MspA porin) that could contribute to the slow growth rate of the slow growers. The genes gained and lost in mycobacteria had eventually helped these bacteria to adapt to different environments and have led to the evolution of the present day rapid and slow growers. Our results also show high number of Mycobacterium abscessus specific genes (811 genes) and some of them are associated with the known bacterial quorum sensing genes that might be important for Mycobacterium abscessus to adapt and survive in variety of unfavorable environments. Mycobacterium abscessus also does not contains genes involved in the bacterial defense system and together with the quorum sensing genes may have contributed to the high gene gain rate of Mycobacterium abscessus.

Author：Douterelo, I;Boxall, JB;Deines, P;Sekar, R;Fish, KE;Biggs, CA

Abstract:The study of the microbial ecology of drinking water distribution systems (DWDS) has traditionally been based on culturing organisms from bulk water samples. The development and application of molecular methods has supplied new tools for examining the microbial diversity and activity of environmental samples, yielding new insights into the microbial community and its diversity within these engineered ecosystems. In this review, the currently available methods and emerging approaches for characterising microbial communities, including both planktonic and biofilm ways of life, are critically evaluated. The study of biofilms is considered particularly important as it plays a critical role in the processes and interactions occurring at the pipe wall and bulk water interface. The advantages, limitations and usefulness of methods that can be used to detect and assess microbial abundance, community composition and function are discussed in a DWDS context. This review will assist hydraulic engineers and microbial ecologists in choosing the most appropriate tools to assess drinking water microbiology and related aspects. (C) 2014 The Authors. Published by Elsevier Ltd.

Author：Chen, X;Sun, YZ;Liu, H;Zhang, L;Li, JQ;Meng, J

Abstract:Ribonucleic acid (RNA) methylation is a type of posttranscriptional modifications occurring in all kingdoms of life. It is strongly related to important biological process, thus making it linked to a number of human diseases. Owing to the development of high-throughput sequencing technology, plenty of achievement had been obtained in RNA methylation research recently. Meanwhile, various computational models have been developed to analyze and mining increasing RNA methylation data. In this review, we first made a brief introduction about eight types of most popular RNA methylation, the biological functions of RNA methylation, the relationship between RNA methylation and disease and five important RNA methylation-related diseases. The research of RNA methylation is based on sequencing data processing, and effective bioinformatics techniques can benefit better understanding of RNA methylation. We further introduced seven publicly available RNA methylation-related databases, and some important publicly available RNA-methylation-related Web servers and software for RNA methylation site identification, differential analysis and so on. Furthermore, we provided detailed analysis of the state-of-the-art computational models used in these Web servers and software. We also analyzed the limitations of these models and discussed the future directions of developing computational models for RNA methylation research.

Author：Jiang, BJ;Zhang, Y;Liu, J;Tsigkou, A;Rapti, M;Lee, MH

Abstract:Metastatic cancer cells express Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) to degrade the extracellular matrix in order to facilitate migration and proliferation. Tissue Inhibitor of Metalloproteinase (TIMP)-2 is the endogenous inhibitor of the MMP. Here, we describe a novel and highly effective fusion strategy to enhance the delivery of TIMP-2 to MT1-MMP. We can reveal that TIMP-2 fused to the haemopexin +/- transmembrane domains of MT1-MMP (two chimeras named T2(PEX+TM) and T2(PEX)) are able to interact with MT1-MMP on the cell surface as well as intracellularly. In the case of T2(PEX+TM), there is even a clear sign of MT1-MMP: T2(PEX+TM) aggregation by the side of the nucleus to form aggresomes. In vitro, T2(PEX+TM) and T2(PEX) suppress the gelatinolytic and invasive abilities of cervical carcinoma (HeLa) and HT1080 fibrosarcoma cancer cells significantly better than wild type TIMP-2. In mouse xenograft, we further demonstrate that T2(PEX) diminishes cervical carcinoma growth by 85%% relative to the control. Collectively, our findings indicate the effectiveness of the fusion strategy as a potential targeted approach in cancer inhibition.

Author：Meng, J;Cui, XD;Liu, H;Zhang, L;Zhang, SW;Rao, MK;Chen, YD;Huang, YF

Abstract:Despite the prevalent studies of DNA/Chromatin related epigenetics, such as, histone modifications and DNA methylation, RNA epigenetics did not receive deserved attention due to the lack of high throughput approach for profiling epitranscriptome. Recently, a new affinity-based sequencing approach MeRIPseq was developed and applied to survey the global mRNA N6-methyladenosine (m(6)A) in mammalian cells. As a marriage of ChIPseq and RNAseq, MeRIPseq has the potential to study, for the first time, the transcriptome-wide distribution of different types of post-transcriptional RNA modifications. Yet, this technology introduced new computational challenges that have not been adequately addressed. We have previously developed a MATLAB-based package 'exomePeak' for detection of RNA methylation sites from MeRIPseq data. Here, we extend the features of exomePeak by including a novel computational framework that enables differential analysis to unveil the dynamics in RNA epigenetic regulations. The novel differential analysis monitors the percentage of modified RNA molecules among the total transcribed RNAs, which directly reflects the impact of RNA epigenetic regulations. In contrast, current available software packages developed for sequencing-based differential analysis such as DESeq or edgeR monitors the changes in the absolute amount of molecules, and, if applied to MeRIPseq data, might be dominated by transcriptional gene differential expression. The algorithm is implemented as an R-package 'exomePeak' and freely available. It takes directly the aligned BAM files as input, statistically supports biological replicates, corrects PCR artifacts, and outputs exome-based results in BED format, which is compatible with all major genome browsers for convenient visualization and manipulation. Examples are also provided to depict how exomePeak R-package is integrated with exiting tools for MeRIPseq based peak calling and differential analysis. Particularly, the rationales behind each processing step as well as the specific method used, the best practice, and possible alternative strategies are briefly discussed. The algorithm was applied to the human HepG2 cell MeRIPseq data sets and detects more than 16000 RNA m(6)A sites, many of which are differentially methylated under ultraviolet radiation. The challenges and potentials of MeRIPseq in epitranscriptome studies are discussed in the end.

Author：Cui, XD;Meng, J;Zhang, SW;Chen, YD;Huang, YF

Abstract:Motivation: N-6-methyl-adenosine (m(6)A) is the most prevalent mRNA methylation but precise prediction of its mRNA location is important for understanding its function. A recent sequencing technology, known as Methylated RNA Immunoprecipitation Sequencing technology (MeRIP-seq), has been developed for transcriptome-wide profiling of m(6)A. We previously developed a peak calling algorithm called exomePeak. However, exomePeak over-simplifies data characteristics and ignores the reads' variances among replicates or reads dependency across a site region. To further improve the performance, new model is needed to address these important issues of MeRIP-seq data. Results: We propose a novel, graphical model-based peak calling method, MeTPeak, for transcriptome-wide detection of m(6)A sites from MeRIP-seq data. MeTPeak explicitly models read count of an m(6)A site and introduces a hierarchical layer of Beta variables to capture the variances and a Hidden Markov model to characterize the reads dependency across a site. In addition, we developed a constrained Newton's method and designed a log-barrier function to compute analytically intractable, positively constrained Beta parameters. We applied our algorithm to simulated and real biological datasets and demonstrated significant improvement in detection performance and robustness over exomePeak. Prediction results on publicly available MeRIP-seq datasets are also validated and shown to be able to recapitulate the known patterns of m(6)A, further validating the improved performance of MeTPeak.