Set Of Analysis Tools Research Articles

Moving translational mass spectrometry imaging towards transparent and reproducible data analyses: a case study of an urothelial cancer cohort analyzed in the Galaxy framework

BackgroundMass spectrometry imaging (MSI) derives spatial molecular distribution maps directly from clinical tissue specimens and thus bears great potential for assisting pathologists with diagnostic decisions or personalized treatments. Unfortunately, progress in translational MSI is often hindered by insufficient quality control and lack of reproducible data analysis. Raw data and analysis scripts are rarely publicly shared. Here, we demonstrate the application of the Galaxy MSI tool set for the reproducible analysis of a urothelial carcinoma dataset.MethodsTryptic peptides were imaged in a cohort of 39 formalin-fixed, paraffin-embedded human urothelial cancer tissue cores with a MALDI-TOF/TOF device. The complete data analysis was performed in a fully transparent and reproducible manner on the European Galaxy Server. Annotations of tumor and stroma were performed by a pathologist and transferred to the MSI data to allow for supervised classifications of tumor vs. stroma tissue areas as well as for muscle-infiltrating and non-muscle infiltrating urothelial carcinomas. For putative peptide identifications, m/z features were matched to the MSiMass list.ResultsRigorous quality control in combination with careful pre-processing enabled reduction of m/z shifts and intensity batch effects. High classification accuracy was found for both, tumor vs. stroma and muscle-infiltrating vs. non-muscle infiltrating urothelial tumors. Some of the most discriminative m/z features for each condition could be assigned a putative identity: stromal tissue was characterized by collagen peptides and tumor tissue by histone peptides. Immunohistochemistry confirmed an increased histone H2A abundance in the tumor compared to the stroma tissues. The muscle-infiltration status was distinguished via MSI by peptides from intermediate filaments such as cytokeratin 7 in non-muscle infiltrating carcinomas and vimentin in muscle-infiltrating urothelial carcinomas, which was confirmed by immunohistochemistry. To make the study fully reproducible and to advocate the criteria of FAIR (findability, accessibility, interoperability, and reusability) research data, we share the raw data, spectra annotations as well as all Galaxy histories and workflows. Data are available via ProteomeXchange with identifier PXD026459 and Galaxy results via https://github.com/foellmelanie/Bladder_MSI_Manuscript_Galaxy_links.ConclusionHere, we show that translational MSI data analysis in a fully transparent and reproducible manner is possible and we would like to encourage the community to join our efforts.

Previsión de la tendencia futura del tipo de cambio EUR/USD, mediante herramientas avanzadas de análisis técnico

Exchange rate forecasting is a major aspect of exchange rate risk hedging. The objective of this research is to propose a procedure to improve the forecasting of the future trend of the exchange rate. In order to achieve the required results, the use of a set of technical analysis tools is proposed, namely: Elliot waves, harmonic patterns and chartist analysis. The main result obtained in this research is that, by means of the proposed tools and the fractality principle, it is possible to forecast the exchange rate regardless of the time horizon to be analyzed.

BivRec: an R package for the nonparametric and semiparametric analysis of bivariate alternating recurrent events

BackgroundBivariate alternating recurrent event data can arise in longitudinal studies where patients with chronic diseases go through two states that occur repeatedly, e.g., care periods and break periods. However, there was no statistical software that provided tools for the analysis of such data. To meet this software need, we developed BivRec, a package for R that contains a set of tools for exploratory, nonparametric and semiparametric regression analysis of bivariate alternating recurrent events.ResultsThe BivRec package provides functions for nonparametric estimations for the joint distribution of bivariate gap times (bivrecNP) and semiparametric regression methods for evaluating covariate effects on the two types of gap times under the accelerated failure time model framework (bivrecReg). The package also provides exploratory data analysis tools such as a visualization of the gap times by groups. We utilize a subset of the South Verona Psychiatric Case Register (PCR) data to illustrate the use of the BivRec package for the reviewed methods.ConclusionsWe demonstrate BivRec’s capability for data visualization, nonparametric and regression based analysis, as well as data simulation. The package has default methods with satisfactory performance despite the complexity of calculations and fills a gap in software for statistical analysis of bivariate alternating recurrent events. BivRec is accessible under the GPL-3 General Public License through CRAN, facilitating its installation.

International Law and (the Critique of) Political Economy

The purpose of this paper is dual, and it has to do with specificity. First, it aims to show that a “law and political economy” approach to international law has been and will be distinct from its US counterpart. To do so, it offers an overview of both the prevailing approaches to and critical engagements with the field. Having shown that neoliberal hegemony is upheld within international law by an admixture of heterogeneous modes of reasoning, the author proceed to argue that this heterogeneity also permeates critical scholarship. This heterogeneity has enabled critical approaches to flourish, but often to the detriment of a consistent, coherent, and purposeful engagement with political economy. The second aim is to show that Marxism offers a distinct and distinctly useful set of analytical tools for international law. Having offered an overview of existing strands of Marxist thought, the author also reflects on the work that remains to be done.

Classification and clustering of RNA crosslink-ligation data reveal complex structures and homodimers.

The recent development and application of methods based on the general principle of "crosslinking and proximity ligation" (crosslink-ligation) are revolutionizing RNA structure studies in living cells. However, extracting structure information from such data presents unique challenges. Here, we introduce a set of computational tools for the systematic analysis of data from a wide variety of crosslink-ligation methods, specifically focusing on read mapping, alignment classification, and clustering. We design a new strategy to map short reads with irregular gaps at high sensitivity and specificity. Analysis of previously published data reveals distinct properties and bias caused by the crosslinking reactions. We perform rigorous and exhaustive classification of alignments and discover eight types of arrangements that provide distinct information on RNA structures and interactions. To deconvolve the dense and intertwined gapped alignments, we develop a network/graph-based tool Crosslinked RNA Secondary Structure Analysis using Network Techniques (CRSSANT), which enables clustering of gapped alignments and discovery of new alternative and dynamic conformations. We discover that multiple crosslinking and ligation events can occur on the same RNA, generating multisegment alignments to report complex high-level RNA structures and multi-RNA interactions. We find that alignments with overlapped segments are produced from potential homodimers and develop a new method for their de novo identification. Analysis of overlapping alignments revealed potential new homodimers in cellular noncoding RNAs and RNA virus genomes in the Picornaviridae family. Together, this suite of computational tools enables rapid and efficient analysis of RNA structure and interaction data in living cells.

DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021update).

DAVID is a popular bioinformatics resource system including a web server and web service for functional annotation and enrichment analyses of gene lists. It consists of a comprehensive knowledgebase and a set of functional analysis tools. Here, we report all updates made in 2021. The DAVID Gene system was rebuilt to gain coverage of more organisms, which increased the taxonomy coverage from 17 399 to 55 464. All existing annotation types have been updated, if available, based on the new DAVID Gene system. Compared with the last version, the number of gene-term records for most annotation types within the updated Knowledgebase have significantly increased. Moreover, we have incorporated new annotations in the Knowledgebase including small molecule-gene interactions from PubChem, drug-gene interactions from DrugBank, tissue expression information from the Human Protein Atlas, disease information from DisGeNET, and pathways from WikiPathways and PathBank. Eight of ten subgroups split from Uniprot Keyword annotation were assigned to specific types. Finally, we added a species parameter for uploading a list of gene symbols to minimize the ambiguity between species, which increases the efficiency of the list upload and eliminates confusion for users. These current updates have significantly expanded the Knowledgebase and enhanced the discovery power of DAVID.

A systematic review on the role of geographical information systems in monitoring and achieving sustainable development goal 6: Clean water and sanitation

AbstractThe world has changed dramatically in the last two decades due to human intervention at regional and global levels. The fates of humanity and our planet are in our hands. Governments, international agencies, the corporate sector, and individuals must work together to shift away from unsustainable practices. The U.N. General Assembly endorsed the 2030 agenda for Sustainable Development, which comprises 17 Sustainable Development Goals (SDGs). Several published research supports SDG strategies in the last 5 years. Despite initial efforts, the U.N. declared that the world is not really on pace to achieve most SDG targets. Geographic information system (GIS) has been identified as an effective tool in accessing, monitoring, and achieving goals that have 15 years lifespan. This paper presents a systematic review of published articles that combined GIS and SDG in their research. Because these 17 goals include 169 targets, the assessment may be more difficult if all the goals were addressed. This study focused only on “SDG 6: Clean water and sanitation” literature. Google scholar was used to find the most relevant 25 studies. The variable attributes like SDG target addressed, study area, monitoring and improving strategies dealt, the particularity of GIS were analyzed in the literature review through content analysis. The systematic review has found that target 6.1 received enormous attention, and the inverse distance weightage (IDW) interpolation tool from the geostatistical analysis toolset was widely employed in the monitoring stage.

SmMIP-tools: a computational toolset for processing and analysis of single-molecule molecular inversion probes-derived data.

MotivationSingle-molecule molecular inversion probes (smMIPs) provide an exceptionally cost-effective and modular approach for routine or large-cohort next-generation sequencing. However, processing the derived raw data to generate highly accurate variants calls remains challenging.ResultsWe introduce SmMIP-tools, a comprehensive computational method that promotes the detection of single nucleotide variants and short insertions and deletions from smMIP-based sequencing. Our approach delivered near-perfect performance when benchmarked against a set of known mutations in controlled experiments involving DNA dilutions and outperformed other commonly used computational methods for mutation detection. Comparison against clinically approved diagnostic testing of leukaemia patients demonstrated the ability to detect both previously reported variants and a set of pathogenic mutations that did not pass detection by clinical testing. Collectively, our results indicate that increased performance can be achieved when tailoring data processing and analysis to its related technology. The feasibility of using our method in research and clinical settings to benefit from low-cost smMIP technology is demonstrated.Availability and implementationThe source code for SmMIP-tools, its manual and additional scripts aimed to foster large-scale data processing and analysis are all available on github (https://github.com/abelson-lab/smMIP-tools). Raw sequencing data generated in this study have been submitted to the European Genome-Phenome Archive (EGA; https://ega-archive.org) and can be accessed under accession number EGAS00001005359.Supplementary information Supplementary data are available at Bioinformatics online.

The FreqTag toolbox: A principled approach to analyzing electrophysiological time series in frequency tagging paradigms

Steady-state visual evoked potential (ssVEP) frequency tagging is an increasingly used method in electrophysiological studies of visual attention and perception. Frequency tagging is suitable for studies examining a wide range of populations, including infants and children. Frequency tagging involves the presentation of different elements of a visual array at different temporal rates, thus using stimulus timing to “tag” the brain response to a given element by means of a unique time signature. Leveraging the strength of the ssVEP frequency tagging method to isolate brain responses to concurrently presented and spatially overlapping visual objects requires specific signal processing methods. Here, we introduce the FreqTag suite of functions, an open source MATLAB toolbox. The purpose of the FreqTag toolbox is three-fold. First, it will equip users with a set of transparent and reproducible analytical tools for the analysis of ssVEP data. Second, the toolbox is designed to illustrate fundamental features of frequency domain and time-frequency domain approaches. Finally, decision criteria for the application of different functions and analyses are described. To promote reproducibility, raw algorithms are provided in a modular fashion, without additional hidden functions or transformations. This approach is intended to facilitate a fundamental understanding of the transformations and algorithmic steps in FreqTag, and to allow users to visualize and test each step in the toolbox.

Spatial Analysis to Justify Urban Decisions in the Planning and Distribution of Green Spaces within the Urban Range of Cities (Case Study of the City of Samawah - Republic of Iraq)

Green spaces represent an important type of urban land use within the urban fabric of the city, and it is of clear importance, like all other patterns. It is an important goal to bring the urban population closer to nature and to provide a suitable external environment for them by creating balance and harmony with nature. Green spaces represent a healthy outlet for humans, increasing their physical and psychological capabilities and are a haven for them to relax and spend their free time. The green areas in the city of Samawah and other cities in Iraq suffer from a clear shortage, as they do not meet the needs of the population in them, in addition to the fact that these areas are fragmented within the city and are not interconnected and do not work as a unified system. Therefore, it is neglected, which leads to the deterioration of the city’s environment and increased air pollution. With population growth and urbanization in the city, there is a negative impact on the natural ecosystem. Therefore, the researchers analyzed the spatial distribution of green areas in the city of Samawah, where the analysis dealt with the percentages of green areas implemented over the years from 2010 - 2020 to determine the amount of dispersal of the assembly using a set of tools for spatial analysis in spatial information systems (GIS). The research field ends with a proposal to identify new green areas in the city. The new green areas will be linked with the existing green areas in the city of Samawa, which will lead to an increase in the open green areas, increase their accessibility and increase social cohesion. In addition, this interconnection will contribute to improving the city’s environment by reducing air pollution and lowering high temperatures during the long summer season. This approach can also achieve other economic benefits when planning an interconnected network of green areas in the city of Samawa.

Maternities: Dorothea Tanning's Aesthetics of Touch

This essay explores the concern in Dorothea Tanning's work of the late 1960s and early 1970s with touch, contiguity, and the concept of maternity. In addition to a series of paintings and drawings that connote intimacy and whose titles allude to maternity, during this period Tanning also gave form to a group of soft sculptures, which similarly evince a preoccupation with closeness and touch, and indicate a form of intimacy that challenges the limits of the individual subject. Tanning's engagement with these themes, the essay argues, resonates closely with the feminist poetics developed around the same time by poststructuralist theorists such as Hélène Cixous, Julia Kristeva, and Luce Irigaray. I propose that Irigaray's theories of maternity, subjectivity, and non‐phallocentric language offer a particularly rich set of analytical tools with which to understand Tanning's work. Through establishing the affinities between Tanning and Irigaray, I suggest, we can better understand the intellectual currents that flowed between poststructuralist feminism and surrealist women's work of this period.

APP accumulates with presynaptic proteins around amyloid plaques: A role for presynaptic mechanisms in Alzheimer's disease?

In Alzheimer's disease (AD), the distribution of the amyloid precursor protein (APP) and its fragments other than amyloid beta, has not been fully characterized. Here, we investigate the distribution of APP and its fragments in human AD brain samples and in mouse models of AD in reference to its proteases, synaptic proteins, and histopathological features characteristic of the AD brain, by combining an extensive set of histological and analytical tools. We report that the prominent somatic distribution of APP observed in control patients remarkably vanishes in human AD patients to the benefit of dense accumulations of extra-somatic APP, which surround dense-core amyloid plaques enriched in APP-Nter. These features are accentuated in patients with familial forms of the disease. Importantly, APP accumulations are enriched in phosphorylated tau and presynaptic proteins whereas they are depleted of post-synaptic proteins suggesting that the extra-somatic accumulations of APP are of presynaptic origin. Ultrastructural analyses unveil that APP concentrates in autophagosomes and in multivesicular bodies together with presynaptic vesicle proteins. Altogether, alteration of APP distribution and its accumulation together with presynaptic proteins around dense-core amyloid plaques is a key histopathological feature in AD, lending support to the notion that presynaptic failure is a strong physiopathological component of AD.

Caffeine Therapy for Apnea of Prematurity: Role of the Circadian CLOCK Gene Polymorphism.

Standard-dose caffeine citrate has been routinely prescribed for apnea of prematurity (AOP) management; however, some preterm infants respond well to the therapy while others do not. The AOP phenotype has been attributed solely to the immature control of the respiratory system consequent to preterm birth, but there are also important genetic influences. Based on our previous report, we tested the hypothesis that the human circadian locomotor output cycles kaput (CLOCK) gene polymorphisms play a role in the response to caffeine citrate therapy in preterm infants. We also studied the interactions of the circadian clock with aryl hydrocarbon receptor (AHR) signaling pathways in preterm babies who received caffeine citrate. This single-center study collected data from 112 preterm infants (<35 weeks gestational age) between July 2017 and July 2018, including apnea-free (n = 48) and apneic (n = 64) groups. Eighty-eight candidate single nucleotide polymorphisms (SNPs) were tested using the MassARRAY system. Association analysis was performed using the PLINK Whole Genome Data Analysis Toolset and SNPStats software. Linkage disequilibrium (LD) and haplotype analyses were performed using Hapview software. No significant intergroup differences in allele distributions or genotype frequencies of CYP1A2, CYP3A4, CYP3A5, and CYP3A7 were detected in our study on preterm babies. Two more SNPs in AHR were found to be associated with determining the response to caffeine citrate therapy in our pediatric patients. Of the 46 candidate SNPs in the CLOCK gene, 26 were found to be associated with determining the response to caffeine treatment in these babies. Interestingly, a significant association was retained for 18 SNPs in the CLOCK gene after false discovery rate correction. Moreover, strong LD formed in those variants in AHR, ADORA2A, and CLOCK genes was confirmed to be significantly associated with a better response to standard-dose caffeine therapy. In summary, CLOCK gene polymorphisms play a role in determining the response to caffeine therapy in premature neonates with AOP. However, whether the AHR and CLOCK signaling pathways crosstalk with each other during caffeine treatment remains largely unclear. Future clinical studies including more immature babies and basic research are needed to explore the mechanism by which circadian rhythms affect the response to caffeine therapy.

Quantifying Phytohormones in Vivo with FRET Biosensors and the FRETENATOR Analysis Toolset.

The ABACUS1-2μ (ABscisic Acid Concentration and Uptake Sensor 1-2μ) and GPS1 (Gibberellin Perception Sensor 1) are direct Förster resonance energy transfer (FRET) biosensors that can be used to measure hormone levels in planta. We provide detailed protocols to image FRET biosensors under exogenously applied hormones in roots, either as a single time point or for treatment time courses before and after hormone application. A new, free, open-source analysis toolset for Fiji is introduced and used to get full 3D segmentation of images of nuclear localized FRET biosensors and calculate emission ratios on a per nucleus basis allowing in-depth analysis of biosensor data.

Prediction of Gene and Genomic Regulation in Candida Species, Using the PathoYeastract Database: A Comparative Genomics Approach.

The ability of living organisms to survive changing environmental conditions is dependent on the implementation of gene expression programs underlying adaptation and fitness. Transcriptional networks can be exceptionally complex: a single transcription factor (TF) may regulate hundreds of genes, and multiple TFs may regulate a single gene-depending on the environmental conditions. Moreover, the same TF may act as an activator or repressor in distinct conditions. In turn, the activity of regulators themselves may be dependent on other TFs, as well as posttranscriptional and posttranslational regulation. These traits greatly contribute to the intricate networks governing gene expression programs.In this chapter, a step-by-step guide of how to use PathoYeastract, one of several interconnecting databases within the YEASTRACT+ portal, to predict gene and genomic regulation in Candida spp. is provided. PathoYeastract contains a set of analysis tools to study regulatory associations in human pathogenic yeasts, enabling: (1) the prediction and ranking of TFs that contribute to the regulation of individual genes; (2) the prediction of the genes regulated by a given TF; and (3) the prediction and ranking of TFs that regulate a genome-wide transcriptional response. These capabilities are illustrated, respectively, with the analysis of: (1) the TF network controlling the C. glabrata QDR2 gene; (2) the regulon controlled by the C. glabrata TF Rpn4; and (3) the regulatory network controlling the C. glabrata transcriptome-wide changes induced upon exposure to the antifungal drug fluconazole. The newest potentialities of this information system are explored, including cross-species network comparison. The results are discussed considering the performed queries and integrated with the current knowledge on the biological data for each case-study.

Unveiling Center‐Type Topological Defects on Rosettes of Lead Zirconate Titanate Associated to Oxygen Vacancies

AbstractUnderstanding the formation of topological defects in ferroelectric materials can provide access to their unusual physics, invaluable for possible applications of domain engineering in nanoelectronics. The present study shows the spontaneous formation of center‐type topological defects in lead zirconate titanate (PZT) films, characterized by a strong in‐plane radial electromechanical response on rosette‐like structures, as revealed by piezoelectric response force microscopy. Multi‐modal electron and X‐ray based techniques provide a comprehensive set of tools for delving at atomic scale the local chemistry, electronic, and crystalline structures. The elemental surface‐sensitivity of soft X‐ray absorption shows chemical segregation and drastic changes in the titanium electronic structure, which have been associated to oxygen vacancies, leading to a mechanism that describe the polarization symmetry on the rosettes. X‐ray nanofluorescence experiments revealed titanium segregation, corroborating with the absorption and low energy electron microscopy images. Taking advantage of a nanobeam, 2D nanodiffraction maps probed the complex microstructure of the domains, revealing its mosaicity and lattice strain at the nanoscale. This study highlights a complex topological structure and provides, by the simultaneous application of a set of analytical tools, a broad comprehension of the formation of center‐type ferroelectric topological defects in PZT.

Capture and Ex-Situ Analysis of Environmental Biofilms in Livestock Buildings.

Little information about biofilm microbial communities on the surface of livestock buildings is available yet. While these spatially organized communities proliferate in close contact with animals and can harbor undesirable microorganisms, no standardized methods have been described to sample them non-destructively. We propose a reproducible coupon-based capture method associated with a set of complementary ex-situ analysis tools to describe the major features of those communities. To demonstrate the biofilm dynamics in a pig farm building, we analyzed the coupons on polymeric and metallic materials, as representative of these environments, over 4 weeks. Confocal laser scanning microscopy (CLSM) revealed a rapid coverage of the coupons with a thick layer of biological material and the existence of dispersed clusters of active metabolic microorganisms. After detaching the cells from the coupons, counts to quantify the CFU/cm2 were done with high reproducibility. High-throughput sequencing of the 16S rRNA V3-V4 region shows bacterial diversity profiles in accordance with reported bacteria diversity in pig intestinal ecosystems and reveals differences between materials. The coupon-based methodology allows us to deepen our knowledge on biofilm structure and composition on the surface of a pig farm and opens the door for application in different types of livestock buildings.

In silico analytical toolset for predictive degradation and toxicity of hazardous pollutants in water sources

Different phenolic compounds, including multimeric lignin derivatives in the β-O-4 form, are among the most prevalent compounds in wastewater, often generated from paper industries. Relatively small concentrations of lignin are hazardous to aquatic organisms and can trigger severe environmental hazards. Herein, we present a predictive toolset to insight the induced toxic hazards prediction, and their Lignin peroxidase (LiP)-assisted degradation mechanism of selected multimeric lignin model compounds. T.E.ST and Toxtree toolset were deployed for toxic hazards estimation in different endpoints. To minimize the concerning hazards, we screened multimeric compounds for binding affinity with LiP. The binding affinity was found to be significantly lower than the reference compound. An Extra precision (XP) Glide score of −6.796 kcal/mol was found for dimer (guaiacyl 4-O-5 guaiacyl) complex as lowest compared to reference compound (−4.007 kcal/mol). The active site residues ASP-153, HIP-226, VAL-227, ARG-244, GLU-215, 239, PHE-261 were identified as site-specific key binding AA residues actively involved with corresponding ligands, forming Hydrophobic, H-Bond, π-Stacking, π-π type interactions. The DESMOND-assisted molecular dynamics simulation's (MDS) trajectories of protein-ligand revealed the considerable binding behavior and attained stability and system equilibrium state. Such theoretical and predictive conclusions indicted the feasibility of LiP assisted sustainable mitigation of lignin-based compounds, and such could be used to protect the environment from the potential hazards posed by recognized similar pollutants.

Changing voices: the changing discourse of ‘religion’ and ‘implicit religious’ language

ABSTRACT Implicit Religion, developed as a set of analytical tools by Edward Bailey, was, in many regards, ahead of its time. Drawing upon the history of Bailey’s Implicit Religion, and its developments since his death, this article will argue that Implicit Religion has something vital to offer to the field of religious studies as the discourse around religion and the study of it continues to shift and reform. Utilising a number of case studies from popular culture, and interviews conducted by those who partake in cosplay, role playing video games, and Straight Edge punk, this article will demonstrate the ways that Implicit Religion can be applied to understand better the changing nature of ‘religious’ language and the importance of paying attention to voices and experiences from the so called ‘secular’ realm.

Implicit religion: reshaping the boundary between the religious and the secular?

ABSTRACT This article introduces a Special Section of Journal of Beliefs and Values focusing on new directions in the study of Implicit Religion. It sets the scene for the Special Section in two steps. Step one focuses the origin of the concept of Implicit Religion as a set of analytic tools for examining the salience of commitments for the lives of individuals in contemporary societies. The tools comprise three key components styled: commitments, integrating foci, and intensive concerns with extensive effects. Step two charts a path through the contributions to the Special Section that apply these tools in respect of the following themes: cosplay, video games, Straight Edge punks, the Grateful Dead, birth stories, sacralised subjugation, TV sitcoms, and attitudes to the body