Extensive Annotation Research Articles

VAReporter: variant reporter for cancer research of massive parallel sequencing

BackgroundHigh throughput sequencing technologies have been an increasingly critical aspect of precision medicine owing to a better identification of disease targets, which contributes to improved health care cost and clinical outcomes. In particular, disease-oriented targeted enrichment sequencing is becoming a widely-accepted application for diagnostic purposes, which can interrogate known diagnostic variants as well as identify novel biomarkers from panels of entire human coding exome or disease-associated genes.ResultsWe introduce a workflow named VAReporter to facilitate the management of variant assessment in disease-targeted sequencing, the identification of pathogenic variants, the interpretation of biological effects and the prioritization of clinically actionable targets. State-of-art algorithms that account for mutation phenotypes are used to rank the importance of mutated genes through visual analytic strategies. We established an extensive annotation source by integrating a wide variety of biomedical databases and followed the American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation and reporting of sequence variations.ConclusionsIn summary, VAReporter is the first web server designed to provide a “one-stop” resource for individual’s diagnosis and large-scale cohort studies, and is freely available at http://rnd.cgu.edu.tw/vareporter.

Delta: a new web-based 3D genome visualization and analysis platform.

Delta is an integrative visualization and analysis platform to facilitate visually annotating and exploring the 3D physical architecture of genomes. Delta takes Hi-C or ChIA-PET contact matrix as input and predicts the topologically associating domains and chromatin loops in the genome. It then generates a physical 3D model which represents the plausible consensus 3D structure of the genome. Delta features a highly interactive visualization tool which enhances the integration of genome topology/physical structure with extensive genome annotation by juxtaposing the 3D model with diverse genomic assay outputs. Finally, by visually comparing the 3D model of the β-globin gene locus and its annotation, we speculated a plausible transitory interaction pattern in the locus. Experimental evidence was found to support this speculation by literature survey. This served as an example of intuitive hypothesis testing with the help of Delta. Delta is freely accessible from http://delta.big.ac.cn, and the source code is available at https://github.com/zhangzhwlab/delta. zhangzhihua@big.ac.cn. Supplementary data are available at Bioinformatics online.

MitoCore: a curated constraint-based model for simulating human central metabolism

BackgroundThe complexity of metabolic networks can make the origin and impact of changes in central metabolism occurring during diseases difficult to understand. Computer simulations can help unravel this complexity, and progress has advanced in genome-scale metabolic models. However, many models produce unrealistic results when challenged to simulate abnormal metabolism as they include incorrect specification and localisation of reactions and transport steps, incorrect reaction parameters, and confounding of prosthetic groups and free metabolites in reactions. Other common drawbacks are due to their scale, making them difficult to parameterise and simulation results hard to interpret. Therefore, it remains important to develop smaller, manually curated models.ResultsWe present MitoCore, a manually curated constraint-based computer model of human metabolism that incorporates the complexity of central metabolism and simulates this metabolism successfully under normal and abnormal physiological conditions, including hypoxia and mitochondrial diseases. MitoCore describes 324 metabolic reactions, 83 transport steps between mitochondrion and cytosol, and 74 metabolite inputs and outputs through the plasma membrane, to produce a model of manageable scale for easy interpretation of results. Its key innovations include a more accurate partitioning of metabolism between cytosol and mitochondrial matrix; better modelling of connecting transport steps; differentiation of prosthetic groups and free co-factors in reactions; and a new representation of the respiratory chain and the proton motive force. MitoCore’s default parameters simulate normal cardiomyocyte metabolism, and to improve usability and allow comparison with other models and types of analysis, its reactions and metabolites have extensive annotation, and cross-reference identifiers from Virtual Metabolic Human database and KEGG. These innovations—including over 100 reactions absent or modified from Recon 2—are necessary to model central metabolism more accurately.ConclusionWe anticipate MitoCore as a research tool for scientists, from experimentalists looking to interpret their data and test hypotheses, to experienced modellers predicting the consequences of disease or using computationally intensive methods that are infeasible with larger models, as well as a teaching tool for those new to modelling and needing a small, manageable model on which to learn and experiment.

CRAVAT 4: Cancer-Related Analysis of Variants Toolkit.

Cancer sequencing studies are increasingly comprehensive and well powered, returning long lists of somatic mutations that can be difficult to sort and interpret. Diligent analysis and quality control can require multiple computational tools of distinct utility and producing disparate output, creating additional challenges for the investigator. The Cancer-Related Analysis of Variants Toolkit (CRAVAT) is an evolving suite of informatics tools for mutation interpretation that includes mutation mapping and quality control, impact prediction and extensive annotation, gene- and mutation-level interpretation, including joint prioritization of all nonsilent mutation consequence types, and structural and mechanistic visualization. Results from CRAVAT submissions are explored in an interactive, user-friendly web environment with dynamic filtering and sorting designed to highlight the most informative mutations, even in the context of very large studies. CRAVAT can be run on a public web portal, in the cloud, or downloaded for local use, and is easily integrated with other methods for cancer omics analysis. Cancer Res; 77(21); e35-38. ©2017 AACR.

RISE: a database of RNA interactome from sequencing experiments.

We present RISE (http://rise.zhanglab.net), a database of RNA Interactome from Sequencing Experiments. RNA-RNA interactions (RRIs) are essential for RNA regulation and function. RISE provides a comprehensive collection of RRIs that mainly come from recent transcriptome-wide sequencing-based experiments like PARIS, SPLASH, LIGR-seq, and MARIO, as well as targeted studies like RIA-seq, RAP-RNA and CLASH. It also includes interactions aggregated from other primary databases and publications. The RISE database currently contains 328,811 RNA-RNA interactions mainly in human, mouse and yeast. While most existing RNA databases mainly contain interactions of miRNA targeting, notably, more than half of the RRIs in RISE are among mRNA and long non-coding RNAs. We compared different RRI datasets in RISE and found limited overlaps in interactions resolved by different techniques and in different cell lines. It may suggest technology preference and also dynamic natures of RRIs. We also analyzed the basic features of the human and mouse RRI networks and found that they tend to be scale-free, small-world, hierarchical and modular. The analysis may nominate important RNAs or RRIs for further investigation. Finally, RISE provides a Circos plot and several table views for integrative visualization, with extensive molecular and functional annotations to facilitate exploration of biological functions for any RRI of interest.

Coreference annotation and resolution in the Colorado Richly Annotated Full Text (CRAFT) corpus of biomedical journal articles

BackgroundCoreference resolution is the task of finding strings in text that have the same referent as other strings. Failures of coreference resolution are a common cause of false negatives in information extraction from the scientific literature. In order to better understand the nature of the phenomenon of coreference in biomedical publications and to increase performance on the task, we annotated the Colorado Richly Annotated Full Text (CRAFT) corpus with coreference relations.ResultsThe corpus was manually annotated with coreference relations, including identity and appositives for all coreferring base noun phrases. The OntoNotes annotation guidelines, with minor adaptations, were used. Interannotator agreement ranges from 0.480 (entity-based CEAF) to 0.858 (Class-B3), depending on the metric that is used to assess it. The resulting corpus adds nearly 30,000 annotations to the previous release of the CRAFT corpus. Differences from related projects include a much broader definition of markables, connection to extensive annotation of several domain-relevant semantic classes, and connection to complete syntactic annotation. Tool performance was benchmarked on the data. A publicly available out-of-the-box, general-domain coreference resolution system achieved an F-measure of 0.14 (B3), while a simple domain-adapted rule-based system achieved an F-measure of 0.42. An ensemble of the two reached F of 0.46. Following the IDENTITY chains in the data would add 106,263 additional named entities in the full 97-paper corpus, for an increase of 76% percent in the semantic classes of the eight ontologies that have been annotated in earlier versions of the CRAFT corpus.ConclusionsThe project produced a large data set for further investigation of coreference and coreference resolution in the scientific literature. The work raised issues in the phenomenon of reference in this domain and genre, and the paper proposes that many mentions that would be considered generic in the general domain are not generic in the biomedical domain due to their referents to specific classes in domain-specific ontologies. The comparison of the performance of a publicly available and well-understood coreference resolution system with a domain-adapted system produced results that are consistent with the notion that the requirements for successful coreference resolution in this genre are quite different from those of the general domain, and also suggest that the baseline performance difference is quite large.

‘La ferme vérité de sa forte agonie’: The Suffering Christ in the Poetry of Jean de La Ceppède

One of the outstanding poetic achievements of the French Counter-Reformation is the sonnet sequence of Jean de La Ceppède (1550-1623), the full title of which is Les Théorèmes sur le sacré mystère de notre Rédemption, and which appeared in a form whose combination of intense formal focus and broad narrative development is particularly appropriate to the subject. The collection, published in two stages (dating from 1613 and 1622) is at once erudite, physical, penitential and precise, under which broad headings it is discussed in the first part of this article, which concentrates on the detailed attention accorded to the specifics of Christ’s suffering body before and during the Crucifixion, often in a strikingly painterly fashion. Two other features stand out: first, the existence of frequently very extensive Annotations, in which the whole panoply of patristic and later erudition is applied to features of the episodes depicted; and, then, the potential for their evocation to serve as meditational and penitential stimuli for the poet persona and, through him, for the reader. The second part of the article turns to the status of the wounds of Christ in the post-Resurrection appearances, as a means of restoring to the risen body some of the previous physical beauty implicitly evoked in the earlier pieces.

De novo RNA sequencing and analysis of the transcriptome of signalgrass (Urochloa decumbens) roots exposed to aluminum

Acidic soils occupy a vast area in the world, and the aluminum (Al) in these soils can directly interact with plant cells and tissues to inhibit their growth and reduce yields. The signalgrass Urochloa decumbens cv. Basilisk (syn. Brachiaria decumbens cv. Basilisk), a widely sown tropical forage grass, is recognized for its high productivity under intensive use, vigorous growth, ease of establishment, and good forage value throughout the year, as well as its exceptional adaptation to infertile acid soils. We sequenced the transcriptome from roots of U. decumbens cv. Basilisk under two conditions, with and without Al, using Illumina paired-end sequencing technology and performed de novo assembly of those reads, which yielded 164,920 transcripts. Of these transcripts, 113,918 were assigned a putative protein function through comparisons with different gene set databases. Additionally, 13,375 simple sequence repeat (SSR) markers were identified. Digital gene expression analyses were conducted to identify 6698 differentially expressed genes between treatments, revealing a great differences in the root transcriptional landscape when exposed to aluminum. An extensive annotation of the differentially expressed genes (DEGs), made possible to identify several transcripts with putative functions correlated to aluminum exposure, most belonging to vesicle transportation, cell wall modifications and metal handling ontologies. In this work, abundant, high-quality transcripts were obtained, providing a reference platform for future biotechnological studies and breeding programs for this species and its close relatives.

Allele-specific expression reveals interactions between genetic variation and environment.

Identifying interactions between genetics and the environment (GxE) remains challenging. We have developed EAGLE, a hierarchical Bayesian model for identifying GxE interactions based on association between environment and allele-specific expression (ASE). Combining RNA-sequencing of whole blood and extensive environmental annotations collected from 922 human individuals, we identified 35 GxE interactions, compared to only four using standard GxE testing. EAGLE provides new opportunities to identify GxE interactions using functional genomic data.

Anne E. Fernald (ed.), Virginia Woolf, Mrs. DallowayVictoria Rosner (ed.), The Cambridge Companion to The Bloomsbury Group

Academia’s fascination with all things Bloomsbury—the collective group of writers and artists who first gathered around the Stephen siblings in a Bloomsbury square in the early 1900s—continues unabated, as the two volumes reviewed here confirm. Virginia Woolf is undoubtedly the most famous writer to emerge from the Bloomsbury group. While Woolf was alive, she herself supervised new editions of her work; since her death, aside from the Hogarth Press originals, there have been numerous other editions of varying quality and consistency. It is only recently, however, that a definitive edition of her works has appeared—The Cambridge Edition of the Works of Virginia Woolf—with two outstanding Woolf scholars, Jane Goldman and Susan Sellers, as general editors. Their mission is to provide a comprehensive, scholarly edition which reveals every detail of composition and publication history, and which includes extensive annotations. Twelve volumes in total are projected, edited by a number of internationally recognized Woolf scholars, covering ten novels, a volume of essays, and a volume of short stories.

The Empire of the Page: Footnotes in Byron’s The Giaour

George Gordon, Lord Byron’s premier Turkish tale, The Giaour (1813), incorporates mock-editorial annotations that push the boundaries of genre and authority within the poem. Byron claims the storyline to be drawn from a Turkish storyteller, which he then translates and remediates into English verse fragments curated with his extensive annotations. Reading the central poetic text as Eastern (fragmented, romantic) and the annotations as Western (linear, objective), this essay emphasizes how margins can be used to subvert and disrupt the narrative of the main page by attempting to unify the narrative as a whole. Byron, in his editorial voice of the notes, seems to take a colonial stance—even while the poem itself remains markedly anti-colonial in tone. The result is what I term “textual imperialism”: the many footnotes force the fragmented Eastern poem into a linear, objective model of Western scholarship.

Multilingual Metaphor Processing: Experiments with Semi-Supervised and Unsupervised Learning

Highly frequent in language and communication, metaphor represents a significant challenge for Natural Language Processing (NLP) applications. Computational work on metaphor has traditionally evolved around the use of hand-coded knowledge, making the systems hard to scale. Recent years have witnessed a rise in statistical approaches to metaphor processing. However, these approaches often require extensive human annotation effort and are predominantly evaluated within a limited domain. In contrast, we experiment with weakly supervised and unsupervised techniques—with little or no annotation—to generalize higher-level mechanisms of metaphor from distributional properties of concepts. We investigate different levels and types of supervision (learning from linguistic examples vs. learning from a given set of metaphorical mappings vs. learning without annotation) in flat and hierarchical, unconstrained and constrained clustering settings. Our aim is to identify the optimal type of supervision for a learning algorithm that discovers patterns of metaphorical association from text. In order to investigate the scalability and adaptability of our models, we applied them to data in three languages from different language groups—English, Spanish, and Russian—achieving state-of-the-art results with little supervision. Finally, we demonstrate that statistical methods can facilitate and scale up cross-linguistic research on metaphor.

Argumentation Mining in User-Generated Web Discourse

The goal of argumentation mining, an evolving research field in computational linguistics, is to design methods capable of analyzing people's argumentation. In this article, we go beyond the state of the art in several ways. (i) We deal with actual Web data and take up the challenges given by the variety of registers, multiple domains, and unrestricted noisy user-generated Web discourse. (ii) We bridge the gap between normative argumentation theories and argumentation phenomena encountered in actual data by adapting an argumentation model tested in an extensive annotation study. (iii) We create a new gold standard corpus (90k tokens in 340 documents) and experiment with several machine learning methods to identify argument components. We offer the data, source codes, and annotation guidelines to the community under free licenses. Our findings show that argumentation mining in user-generated Web discourse is a feasible but challenging task.

Book Review: James Braxton Peterson, Hip-Hop Headphones: A Scholar’s Critical Playlist

Book Review: James Braxton Peterson, Hip-Hop Headphones: A Scholar's Critical Playlist. New York: Bloomsbury Academic, 2016. ISBN: 978-1501308246 (Paperback). 296 Pages. $29.95.[Article copies available for a fee from The Transformative Studies Institute. E-mail address: journal@transformativestudies.org Website: http://www.transformativestudies.org ©2017 by The Transformative Studies Institute. All rights reserved.]Since its pioneering stages during the 1990s the field of Hip Hop Studies made steady progression. Breakthrough works such as Houston Baker's Black Studies, Rap, and the Academy (1993) and Tricia Rose's Black Noise (1994) examined hop culture with nuance and verve and, importantly, a knowledged perspective. Along with the emergence of prolific hip hop intellectuals such as Michael Eric Dyson, Mark Anthony Neal and Joan Morgan, to name a few, such efforts not only expounded upon the particulars of hop culture but crucially created paths of investigation in which issues of race, gender and class stratification endemic to all of American society could be better understood.Embodying both the fierce intellect of his predecessors and promoting the of hop culture and education is James Braxton Peterson, professor of English and director of Africana Studies at Lehigh University. For Peterson, this marriage is already embedded into the very fabric of hop culture, its history, structure and modus operandi; it is we academics who have often posed indifferent to youth culture and must endeavor ourselves to be brave, bold and studied enough to come to the party. With the hopes of becoming a staple resource for all educators who are in interested in and committed to teaching the history, artistry and culture of Hip Hop at all levels of education, Braxton's newest book, Hip-Hop Headphones: A Scholar's Critical Playlist is an invitation to interested scholars- an almost how-to manual to jump start inquiry in the field. In addition, the text serves as depository of essential tools of the trade: hip-hop syllabi, purposefully themed playlists and an extensive bibliography and annotations all provide meaningful direction to exploration of hop culture in the classroom.As Peterson notes, beyond publications, Hip Hop Studies (or #HipHopEd to the cognoscenti) has developed via the dual pressures of Hip-Hop Generational scholars entering the academy as as graduate students and more recently as professors and the steady pressure, interest, and inclinations of younger Hip Hop generational students who continue to find Hip-Hop-related courses of vital interest in their graduate studies. (26) Indeed, in the past ten years, hop made its presence felt in the hallowed halls of Harvard with its Hiphop Archive and Research Institute and most certainly the classroom where hop culture cross pollinates with the disciplines of English, history, political science, religion and philosophy, sociology and anthropology, not to mention music, performance theater and the arts. Duke University even tapped the talents of renowned hop beat maker, 9th Wonder as an adjunct instructor. Apparently, knowledge reigns supreme over nearly everyone.And not unlike other disciplines, there are recommended- if not required- methodologies Peterson suggests to organize pedagogy and learning. Foremost, the author advocates critical listening a tact he aligns with critical thinking; a deliberate effort to use our ears and intellect to tune in to hop music's multilayered texts that are most easily evidenced in rap lyrics but can also be found in video imaging, marketing and popular discourses interacting with the culture in news and social media and the academy. Peterson's reasoning for taking hop music seriously cites the culture and its practitioners prescient ability to identify and chronicle America's complex social problems: the challenges of a post industrialized economy for the working poor, the travails of urban ecology, limited access to educational and employment opportunities and failed and devastating Wars on Poverty, Drugs and Terrorism. …

Telling Tales and Crafting Books: Essays in Honor of Thomas H. Ohlgren ed. by Alexander L. Kaufman, Shaun F.D. Hughes, and Dorsey Armstrong

ALEXANDER L. KAUFMAN, SHAUN F.D. HUGHES, and DORSEY ARMSTRONG, eds., Telling Tales and Crafting Books: Essays in Honor of Thomas H. Ohlgren. Studies in Medieval and Early Modern Culture: Festschriften, Occasional Papers, and Lectures Vol. 24. Kalamazoo: Medieval Institute Publications, 2016. Pp. 386. ISBN: 978-1-58044219-0. $99.Telling Tales and Crafting Books celebrates the works and interests of Purdue University's eminent medievalist Thomas Ohlgren. Like the scholar himself, the volume is remarkably coherent, embracing collaboration and exploring topics deeply, while also providing insightful introductory surveys for new audiences. Kaufman, Hughes, and Armstrong have mirrored Ohlgren's interests, teaching, and deep learning in the volume quite remarkably. The book is divided into three parts, representative of Ohlgren's major research interests: 'Old English and the North'; 'Robin Hood'; and 'Books and Literature.' Each section contains at least one essay suitable for use in undergraduate classrooms, and several would be excellent for graduate courses. The research and learning on display in each piece is impressive, providing readers with extensive annotations and discussion, alongside deep bibliographies.Kaufman's 'Introduction' (1-19) reveals many of these connections, and provides an excellent overview of Ohlgren's fascination with story and narrative: the value and potency of the tale in 'its ability to create a lasting impression on readers, both medieval and modern' (1). For readers whose exposure to Ohlgren's work has been within a particular period, author, or area of study, this is helpful context for understanding the scholar and, of course, the range of essays in the volume. Moreover, Ohlgren's exploration of the tale's potential to engage and delight allows Kaufman et al. to present the volume as continuing the work of both scholar and tale: the essays can be read as individual pieces, of course, but taken together they become a conversation. The volume encourages readers to become medieval: an active audience that recognizes that 'the more one invested oneself in the tale, the more mirth-entertainment, education, consolation, inspiration-one could possibly have as a result' (3).Part I of Telling Tales and Crafting Books focuses upon Anglo-Saxon (and Old Norse) tales and art. The five essays in 'Old English and the North' are all fascinating, but Eric R. Carlson's 'Grendel as Novelistic Outlaw-Hero: A Girardian Reading' (23-47) is a standout for its accessibility. The essay not only addresses a common classroom dilemma-student dislike for the hero Beowulf and contranarrative sympathy, even admiration, for the villain Grendel-but also provides an explanation that will challenge but ultimately reward undergraduates. The next essay is better suited for graduate study or engagement by specialist scholars: Shaun F.D. Hughes' 'The Evolution of Monster Fights: From Beowulf versus Grendel to Jon Gudmundssson laerSi versus Snaefjalladraugur and Beyond' (49-91) connects the motif of wrestling an undead creature-the draugur, a ghost inhabiting a material form-to the Beowulf story by highlighting the uncivilized wilderness spaces in which these combats occur. Thomas Ohlgren's fascination with the North has not been limited to the literary: as Kaufman reminds us throughout the 'Introduction,' one of Ohlgren's great contributions has been insistence on context, and his Bodleian Slide Collection provided many students and colleagues with visual reminders that medieval literature used art as well as words to tell tales (3-4). Thus, the next two essays in this section, J.A. Jackson's 'Salvation Twice Told: Idolatry, Typology, and Repentance in Genesis B' (93-117) and Molly A. Martin's 'Vision and Sex in the Iconography of the Old English Genesis Manuscript' (119-38) focus on the confluence of word and image. Martin's 'Vision and Sex' follows Jackson's piece, a slightly problematic organizational choice since Jackson's essay references photographs of the Genesis manuscript printed several pages later in Martin. …

M47 - Whole Exome Sequencing of Affected Individuals From Large Consanguineous Pedigrees With Psychotic/Affective Disorders From Pakistan

Background For historical, religious, cultural, and social reasons, Pakistan has the highest rate of consanguineous marriage in the world, which have generated some large multiplex pedigrees clustering severely affected individuals with major psychiatric disorders. Such large consanguineous unions may offer a unique opportunity to identify, and characterize genetic risk factors associated with severe psychotic/affective disorders, as well as the mode of inheritance and underlying genetic mechanisms. Methods 10 multiplex pedigrees aggregated with psychotic/affective disorders were included in the study. Exome capturing was performed using Agilent SureSelect™ Human All Exon Kits for 118 affected individuals, and sequenced by HiSeq2000 at McGill University and Genome Quebec Innovation Centre. Sequence data was processed, aligned and variants called using standard bioinformatic pipeline, with extensive relevant annotations, including the functional effects and deleteriousness of the variants, population frequencies, and relevant phenotypic information. Results I. Selection of potential candidate variants/genes: (1) In total, 846,266 variants were identified in 118 exomes of affected individuals from 10 large pedigrees. 10,687 potential deleterious variants were selected, including nonsense, frameshift indels, splicing variants and predicted damaging missense, comprising of 2,414 novel variants and 8273 rare and novel variants. (2) We used in-house controls to exclude false positives which were generated by sequencing platform. (3) South-Asian population minor allele frequency from public database was used as references for population-specific variants. (4) We further selected candidate variants locating in evolutionary constraint genes. (5) Genes expressed in the brain tissue were prioritized. (6) Gene-set enrichment analyses of the final candidate list identified gene sets over-representing in brain functional pathways, which may have an implication with the disease phenotypes in each pedigree. II. Validations: individual-, pedigree- and population- specific novel and rare deleterious variants have been selected for further bioinformatic characterization. Discussion (1) rare/novel deleterious variants are mostly heterozygote variants, exclusion of monogenic recessive variant in each pedigree; (2) rare/novel deleterious variants are mostly individual, family and population specific variants; (3) aggregation of novel/rare variants in each affected individuals and pedigree; and segregation and gene-set enrichment analyses indicate polygenic mode of inheritance and specific gene network(s) involved. Genetic validation through targeted resequencing of selected variants in family and population controls through a MiSeq-MIP (molecular inversion probe) platform and subsequent family-based statistical analyses are underway.

Construction of the Leaf Senescence Database and Functional Assessment of Senescence-Associated Genes.

Leaf senescence is the last phase of plant development and a highly coordinated process regulated by a large number of senescence-associated genes (SAGs). By broad literature survey, we constructed a leaf senescence database (LSD) in 2011 and updated it to Version 2.0 in 2014 ( http://www.eplantsenescence.org/ and http://psd.cbi.pku.edu.cn/ ) which contains a total of 5357 genes and 324 mutants from 44 species. These SAGs were retrieved based on genetic, genomic, proteomic, physiological, or other experimental evidence and were classified into different categories according to their functions in leaf senescence or morphological phenotype of mutants. To provide comprehensive information for SAGs, we made extensive annotation by both manual and computational approaches. In addition, we predicted putative orthologues of the SAGs in other species. LSD has a user-friendly interface to allow users to make text queries or BLAST searches and to download SAGs sequences for local analysis. Functional analyses of putative SAGs reveal that WRKY75, AZF2, NAC16, and WRKY26 are positive regulators of leaf senescence, while MKP2 and CTR1 perform negative regulation to leaf senescence. This database has been served as a valuable resource for basic research on the function of SAGs and evolution of plant leaf senescence, as well as for the exploration of genetic traits in agronomically important plants.

The relationship between relative solvent accessible surface area (rASA) and irregular structures in protean segments (ProSs).

Intrinsically Disordered Proteins (IDPs) lack a stable, three-dimensional structure under physiological conditions, yet they exhibit numerous biological activities. Protean segments (ProSs) are the functional regions of intrinsically disordered proteins that undergo disorder-to-order transitions upon binding to their partners. Example ProSs collected from the intrinsically disordered proteins with extensive annotations and literature (IDEAL) database. The interface of protean segments (ProSs) is classified into core, rim, and support, and analyzed their secondary structure elements (SSEs) based on the relative accessible surface area (rASA). The amino acid compositions and the relative solvent accessible surface areas (rASAs) of ProS secondary structural elements (SSEs) at the interface, core and rim were compared to those of heterodimers. The average number of contacts of alpha helices and irregular residues was calculated for each ProS and heterodimer. Furthermore, the ProSs were classified into high and low efficient based on their average number of contacts at the interface. The results indicate that the irregular structures of ProSs and heterodimers are significantly different. The rASA of irregular structures in the monomeric state (rASAm) is large, leads to the formation of larger ΔrASA and many contacts in ProSs.

Combination of RNA- and exome sequencing: Increasing specificity for identification of somatic point mutations and indels in acute leukaemia

Handling of large data sets from whole exome sequencing is a challenge, not the least because of the high risk of detecting false positive variants. Furthermore, there is still no consensus regarding what stage filtering of variants is performed in the bioinformatics pipeline to produce consistent result sets, the extent of filtering and how this is most optimal performed. We hypothesized that combination of coding transcriptome and exomes enables precise identification of both somatic single nucleotide and indel variants early in the bioinformatics process, superseding the need for extensive annotation and validation from external databases.Exome and RNA-sequencing were performed on diagnosis-remission paired bone marrow samples from 5 cytogenetically normal AML, i.e. sequencing of 20 samples in total. Intersection of rare exome and RNA variants, exclusively found in the diagnostic samples, yielded a median of 6 somatic point mutations and small indels, ranging from 3 to 21. Close correlation between routine diagnostic biomarkers was observed in 29/30 laboratory tests, with the exception of a large FLT3 internal tandem repeat, whereas WT1 with nonsense mutation lacked RNA transcripts. Additionally, the assay revealed mutations in DNMT3A, IDH2, TET2 and IL32 frame shift, not encompassed by routine panel.We thus describe a procedure to effectively reduce observations to a focused subset of high specificity. The approach is applicable to precise screening of both putative driver mutations and, often heterogeneous, discrete patient specific somatic combinations.

Annotations in copies of Thomas Johnson's Mercurius botanicus (1634) and Mercurii botanici, pars altera (1641): authorship and provenance

By an analysis of extensive and detailed annotations in copies of Thomas Johnson's Mercurius botanicus (1634) and Mercurii botanici, pars altera (1641) held in the library of the Royal Botanic Gardens, Kew, the probable author is identified as William Bincks, an apprentice apothecary of Kingston-upon-Thames, Surrey. Through Elias Ashmole, a friend of Bincks' master Thomas Agar, a link is established with the probable original owner, John Watlington of Reading, botanist and apothecary, and colleague of Thomas Johnson. The route by which the book ended up in the hands of Thomas Wilson, a journeyman copyist of Leeds, is suggested. Plants growing near Kingston-upon-Thames in the late seventeenth century, recorded in manuscript, are noted, many being first records for the county of Surrey.