Improved prediction of RNA secondary structure by integrating the free energy model with restraints derived from experimental probing data.

PublishedEvaluation StudiesJournal ArticleResearch Support, Non-U.S. Gov'tRecently, several experimental techniques have emerged for probing RNA structures based on high-throughput sequencing. However, most secondary structure prediction tools that incorporate probing data are designed and optimized for particular types of experiments. For example, RNAstructure-Fold is optimized for SHAPE data, while SeqFold is optimized for PARS data. Here, we report a new RNA secondary structure prediction method, restrained MaxExpect (RME), which can incorporate multiple types of experimental probing data and is based on a free energy model and an MEA (maximizing expected accuracy) algorithm. We first demonstrated that RME substantially improved secondary structure prediction with perfect restraints (base pair information of known structures). Next, we collected structure-probing data from diverse experiments (e.g. SHAPE, PARS and DMS-seq) and transformed them into a unified set of pairing probabilities with a posterior probabilistic model. By using the probability scores as restraints in RME, we compared its secondary structure prediction performance with two other well-known tools, RNAstructure-Fold (based on a free energy minimization algorithm) and SeqFold (based on a sampling algorithm). For SHAPE data, RME and RNAstructure-Fold performed better than SeqFold, because they markedly altered the energy model with the experimental restraints. For high-throughput data (e.g. PARS and DMS-seq) with lower probing efficiency, the secondary structure prediction performances of the tested tools were comparable, with performance improvements for only a portion of the tested RNAs. However, when the effects of tertiary structure and protein interactions were removed, RME showed the highest prediction accuracy in the DMS-accessible regions by incorporating in vivo DMS-seq data.National Key Basic Research Program of China [2012CB316503]; National High-Tech Research and Development Program of China [2014AA021103]; National Natural Science Foundation of China [31271402]; Tsinghua University Initiative Scientific Research Program [2014z21045]; Hong Kong Research Grants Council Early Career Scheme [419612 to K.Y.]; National Science Foundation [1339282 to D.H.M.]; Computing Platform of the National Protein Facilities (Tsinghua University). Funding for open access charge: National Natural Science Foundation of China [31271402]

Genetic Diversity in the Australian Strawberry Breeding Program

The ASBP selects and releases varieties for three diverse climatic regions: the subtropical, temperate and Mediterranean environments. Adeliberate consideration in all breeding programs is to maintain genetic diversity within and across sub-programs. Prior to the development of genomic information and access to inexpensive molecular marker technology, genetic diversity in breeding programs was managed through a thorough understanding of the ancestral relationships between breeding lines, known as pedigree information.In the last decade, two single nucleotide polymorphism (SNP) arrays for strawberries (a 90K (Bassil et al., 2015) and then a 35K (Verma et al., 2017)) have been developed that provide cost effective high-throughput genotyping. The ASBP commenced routine genotyping in 2018 with SNP data now available for ~1000 samples including lines from all three target environments, early and advanced material, released varieties, a few external lines, and seedling material from the powdery mildew screening nursery.The results from this analysis will help the breeders guard against unnecessary narrowing of the genetic diversity in the breeding pipeline and further leverage the diversity within and across the sub-programs and target environments

Genetic Diversity in the Australian Strawberry Breeding Program

The ASBP selects and releases varieties for three diverse climatic regions: the subtropical, temperate and Mediterranean environments. Adeliberate consideration in all breeding programs is to maintain genetic diversity within and across sub-programs. Prior to the development of genomic information and access to inexpensive molecular marker technology, genetic diversity in breeding programs was managed through a thorough understanding of the ancestral relationships between breeding lines, known as pedigree information.In the last decade, two single nucleotide polymorphism (SNP) arrays for strawberries (a 90K (Bassil et al., 2015) and then a 35K (Verma et al., 2017)) have been developed that provide cost effective high-throughput genotyping. The ASBP commenced routine genotyping in 2018 with SNP data now available for ~1000 samples including lines from all three target environments, early and advanced material, released varieties, a few external lines, and seedling material from the powdery mildew screening nursery.The results from this analysis will help the breeders guard against unnecessary narrowing of the genetic diversity in the breeding pipeline and further leverage the diversity within and across the sub-programs and target environments

Special Libraries, April 1919

Volume 10, Issue 3https://scholarworks.sjsu.edu/sla_sl_1919/1002/thumbnail.jp

Boundary work: An interpretive ethnographic perspective on negotiating and leveraging cross-cultural identity

The complexity of global organizations highlights the importance of members’ ability to span diverse boundaries that may be defined by organization structures, national borders, and/or a variety of cultures associated with organization, nation-based societal and work cultures, industries, and/or professions. Based on ethnographic research in a Japan–US binational firm, the paper describes and analyzes the boundary role performance of the firm\u27s Japanese members. It contributes toward theory on boundary spanning by introducing a “cultural identity negotiation” conceptual framework. We show boundary spanning as a process shaped through the interplay of the contextual issues that make a boundary problematic; an individual\u27s multiple repertoires of cultural knowledge; and the individual boundary spanner\u27s “negotiation”, through interaction with others, of his/her cultural identities – the sense of “who I am” as a cultural being that is fundamental to an individual\u27s self-concept. At the same time, we make transparent the epistemological and methodological foundations of an interpretive ethnographic approach, demonstrating its value for understanding complex organizational processes. Research findings have practical implications for the selection and training of an organization\u27s employees, particularly of persons who may be considered “bicultural”

The CIMMYT Australia ICARDA Germplasm Evaluation concept: a model for international cooperation and impact

Bread wheat germplasm is accessed from the International Maize and Wheat Improvement Centre (CIMMYT) and the International Centre for Agricultural Research in the Dry Areas (ICARDA) by Australian wheat breeders and researchers through the CIMMYT Australia ICARDA Germplasm Evaluation (CAIGE) program. The CAIGE program coordinates the selection, importation, quarantine, dissemination, and evaluation of the imported bread wheat germplasm and the management of associated data and information. This paper describes the CAIGE model and assesses both the genetic and economic impacts of these materials on the Australian wheat industry after commercialisation of wheat breeding in the early 21st century and the establishment of CAIGE. The CAIGE concept was validated using data collected and analysed from multi-environment trials between 2017 and 2020. The impact of cultivars with and without CAIGE contribution to pedigree on yield was estimated using production-by-variety statistics. Net gain in yield, estimated as the yield difference between CAIGE and Non-CAIGE varieties, was multiplied by the percentage contribution to pedigree to estimate the additional yield. The CAIGE bread wheat program identified diverse, high-yielding, and disease-resistant germplasm and significantly improved the capture and dissemination of information. The benefit-cost ratio, calculated as the sum of benefits divided by investments, indicated that, for every dollar invested in CAIGE, a further $20 was generated in benefits. The internal rate of return was estimated at 163% and the modified rate at 18%. The benefits of these international materials to Australian wheat breeding remained significant

HPV16 variant lineage, clinical stage, and survival in women with invasive cervical cancer

Background: HPV16 variants are associated with different risks for development of CIN3 and invasive cancer, although all are carcinogenic. The relationship of HPV 16 variants to cancer survival has not been studied. Methods: 155 HPV16-positive cervical cancers were categorized according to European and non-European variant patterns by DNA sequencing of the E6 open reading frame. Clinico-pathologic parameters and clinical outcome were collected by chart review and death registry data. Results: Of the 155 women (mean age 44.7 years; median follow-up 26.7 months), 85.2% harbored European variants while 14.8% had non-European sequences. HPV16 variants differed by histologic cell type (p = 0.03) and stage (1 vs. 2+; p = 0.03). Overall, 107 women (68.0%) were alive with no evidence of cancer, 42 (27.1%) died from cervical cancer, 2 (1.3%) were alive with cervical cancer, and 4 (2.6%) died of other causes. Death due to cervical cancer was associated with European variant status (p < 0.01). While 31% of women harboring tumors with European variants died from cervical cancer during follow-up, only 1 of 23 (4.4%) non-European cases died of cancer. The better survival for non-European cases was partly mediated by lower stage at diagnosis. Conclusions: Overall, invasive cervical cancers with non-European variants showed a less aggressive behavior than those with European variants. These findings should be replicated in a population with more non-European cases

A genome for gnetophytes and early evolution of seed plants

Genome sequencing, assembly and annotation were conducted by the Novogene Bioinformatics Institute, Beijing, China; mutual contracts were No. NHT140016 and NVT140016004. This work was supported by funding from the Scientific Project of Shenzhen Urban Administration (201519) and a Major Technical Research Project of the Innovation of Science and Technology Commission of Shenzhen (JSGG20140515164852417). Additional funding was provided in particular by the Scientific Research Program of Sino-Africa Joint Research Center (SAJL201607). We thank X.Q. Wang, G.W. Hu, Z.D. Chen and Y.H. Guo for comments on gnetophyte phylogenetic relationships and ecological issues; H. Wu and X.P. Ning for discussion of related organ development; K.K. Wan and S. Sun for additional help on the analysis of repeats. We also thank X.Y. for support of funding coordination. Y.V.d.P. acknowledges the Multidisciplinary Research Partnership ‘Bioinformatics: from nucleotides to networks’ Project (no. 01MR0310W) of Ghent University, and funding from the European Union Seventh Framework Programme (FP7/2007-2013) under European Research Council Advanced Grant Agreement 322739-DOUBLEUP

Differential serotonin transport is linked to the rh5-HTTLPR in peripheral blood cells

The human serotonin transporter (SERT) gene possesses a 43-base pair (bp) insertion-deletion promoter polymorphism, the h5-HTTLPR. Genotype at this locus correlates with variation in anxiety-related personality traits and risk for major depressive disorder in many studies. Yet, the complex effects of the h5-HTTLPR, in combination with closely associated single-nucleotide polymorphisms (SNPs), continue to be debated. Moreover, although SERT is of high clinical significance, transporter function in vivo remains difficult to assess. Rhesus express a promoter polymorphism related to the h5-HTTLPR. The rh5-HTTLPR has been linked to differences in stress-related behavior and cognitive flexibility, although allelic variations in serotonin uptake have not been investigated. We studied the serotonin system as it relates to the 5-HTTLPR in rhesus peripheral blood cells. Sequencing of the rh5-HTTLPR revealed a 23-bp insertion, which is somewhat longer than originally reported. Consistent with previous reports, no SNPs in the rh5-HTTLPR and surrounding genomic regions were detected in the individuals studied. Reductions in serotonin uptake rates, cell surface SERT binding, and 5-hydroxyindoleacetic acid/serotonin ratios, but not SERT mRNA levels, were associated with the rh5-HTTLPR short allele. Thus, serotonin uptake rates are differentiable with respect to the 5-HTTLPR in an easily accessible native peripheral tissue. In light of these findings, we foresee that primary blood cells, in combination with high sensitivity functional measurements enabled by chronoamperometry, will be important for investigating alterations in serotonin uptake associated with genetic variability and antidepressant responsiveness in humans

The ITS1-5.8S-ITS2 Sequence Region in the Musaceae: Structure, Diversity and Use in Molecular Phylogeny

Genes coding for 45S ribosomal RNA are organized in tandem arrays of up to several thousand copies and contain 18S, 5.8S and 26S rRNA units separated by internal transcribed spacers ITS1 and ITS2. While the rRNA units are evolutionary conserved, ITS show high level of interspecific divergence and have been used frequently in genetic diversity and phylogenetic studies. In this work we report on the structure and diversity of the ITS region in 87 representatives of the family Musaceae. We provide the first detailed information on ITS sequence diversity in the genus Musa and describe the presence of more than one type of ITS sequence within individual species. Both Sanger sequencing of amplified ITS regions and whole genome 454 sequencing lead to similar phylogenetic inferences. We show that it is necessary to identify putative pseudogenic ITS sequences, which may have negative effect on phylogenetic reconstruction at lower taxonomic levels. Phylogenetic reconstruction based on ITS sequence showed that the genus Musa is divided into two distinct clades – Callimusa and Australimusa and Eumusa and Rhodochlamys. Most of the intraspecific banana hybrids analyzed contain conserved parental ITS sequences, indicating incomplete concerted evolution of rDNA loci. Independent evolution of parental rDNA in hybrids enables determination of genomic constitution of hybrids using ITS. The observation of only one type of ITS sequence in some of the presumed interspecific hybrid clones warrants further study to confirm their hybrid origin and to unravel processes leading to evolution of their genomes