Linking big biomedical datasets to modular analysis with Portable Encapsulated Projects

Background Organizing and annotating biological sample data is critical in data-intensive bioinformatics. Unfortunately, metadata formats from a data provider are often incompatible with requirements of a processing tool. There is no broadly accepted standard to organize metadata across biological projects and bioinformatics tools, restricting the portability and reusability of both annotated datasets and analysis software. Results To address this, we present the Portable Encapsulated Project (PEP) specification, a formal specification for biological sample metadata structure. The PEP specification accommodates typical features of data-intensive bioinformatics projects with many biological samples. In addition to standardization, the PEP specification provides descriptors and modifiers for project-level and sample-level metadata, which improve portability across both computing environments and data processing tools. PEPs include a schema validator framework, allowing formal definition of required metadata attributes for data analysis broadly. We have implemented packages for reading PEPs in both Python and R to provide a language-agnostic interface for organizing project metadata. Conclusions The PEP specification is an important step toward unifying data annotation and processing tools in data-intensive biological research projects. Links to tools and documentation are available at http://pep.databio.org/.

Determination of a six-gene prognostic model for cervical cancer based on WGCNA combined with LASSO and Cox-PH analysis

Aim This study aimed to establish a risk model of hub genes to evaluate the prognosis of patients with cervical cancer. Methods Based on TCGA and GTEx databases, the differentially expressed genes (DEGs) were screened and then analyzed using GO and KEGG analyses. The weighted gene co-expression network (WGCNA) was then used to perform modular analysis of DEGs. Univariate Cox regression analysis combined with LASSO and Cox-pH was used to select the prognostic genes. Then, multivariate Cox regression analysis was used to screen the hub genes. The risk model was established based on hub genes and evaluated by risk curve, survival state, Kaplan-Meier curve, and receiver operating characteristic (ROC) curve. Results We screened 1265 DEGs between cervical cancer and normal samples, of which 620 were downregulated and 645 were upregulated. GO and KEGG analyses revealed that most of the upregulated genes were related to the metastasis of cancer cells, while the downregulated genes mostly acted on the cell cycle. Then, WGCNA mined six modules (red, blue, green, brown, yellow, and gray), and the brown module with the most DEGs and related to multiple cancers was selected for the follow-up study. Eight genes were identified by univariate Cox regression analysis combined with the LASSO Cox-pH model. Then, six hub genes (SLC25A5, ENO1, ANLN, RIBC2, PTTG1, and MCM5) were screened by multivariate Cox regression analysis, and SLC25A5, ANLN, RIBC2, and PTTG1 could be used as independent prognostic factors. Finally, we determined that the risk model established by the six hub genes was effective and stable. Conclusions This study supplies the prognostic value of the risk model and the new promising targets for the cervical cancer treatment, and their biological functions need to be further explored.

Dynamic co-expression modular network analysis in nonalcoholic fatty liver disease

Background Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease affecting people’s health worldwide. Exploring the potential biomarkers and dynamic networks during NAFLD progression is urgently important. Material and methods Differentially expressed genes (DEGs) in obesity, NAFL and NASH were screened from GSE126848 and GSE130970, respectively. Gene set enrichment analysis of DEGs was conducted to reveal the Gene Ontology (GO) biological process in each period. Dynamic molecular networks were constructed by DyNet to illustrate the common and distinct progression of health- or obesity-derived NAFLD. The dynamic co-expression modular analysis was carried out by CEMiTool to elucidate the key modulators, networks, and enriched pathways during NAFLD. Results A total of 453 DEGs were filtered from obesity, NAFL and NASH periods. Function annotation showed that health-NAFLD sequence was mainly associated with dysfunction of metabolic syndrome pathways, while obesity-NAFLD sequence exhibited dysregulation of Cell cycle and Cellular senescence pathways. Nine nodes including COL3A1, CXCL9, CYCS, CXCL10, THY1, COL1A2, SAA1, CDKN1A, and JUN in the dynamic networks were commonly identified in health- and obesity-derived NAFLD. Moreover, CYCS, whose role is unknown in NAFLD, possessed the highest correlation with NAFLD activity score, lobular inflammation grade, and the cytological ballooning grade. Dynamic co-expression modular analysis showed that module 4 was activated in NAFL and NASH, while module 3 was inhibited at NAFLD stages. Module 3 was negatively correlated with CXCL10, and module 4 was positively correlated with COL1A2 and THY1. Conclusion Dynamic network analysis and dynamic gene co-expression modular analysis identified a nine-gene signature as the potential key regulator in NAFLD progression, which provided comprehensive regulatory mechanisms underlying NAFLD progression.

A phonological reanalysis of morphological segment deletion and de-affrication in Ik

Ik presents a widespread pattern of allomorphy characterised by morpheme-specific segment-zero alternations (deletions) and de-affrication. Part of the process is clearly phonological because it applies to every item in the language. Final vowels are devoiced into oblivion, though they are always recoverable in Non-Domain-Final context. Case allomorphy shows various item-specific patterns, some affixes overwrite the final-vowels of roots, others do not, and others yet exhibit consonant-zero alternations. Meanwhile, interestingly, there is (ostensibly) morphologically-sensitive consonant deletion that is fully complementary with what is clearly phonological vowel deletion. In fact, an entirely phonological analysis is possible if the consonant-zero alternations are modelled by floating consonants belonging to the exponents of certain morphemes. Therefore, the item/morpheme-specific aspect of the process is actually specific to the exponent of that morpheme. This locates the whole analysis in the phonology and provides a straightforward account of the complementarity of the two deletion processes. The formal analysis is very close to what has been proposed for French, with its floating consonants and its irregular hiatus-driven vowel deletion. The analysis will then be extended to the item-specific idiosyncratic process of de-affrication that is blocked, not by coincidence, precisely in morphologically overwriting environments. In the end, all the phenomena can be accounted for in a modular analysis, provided one gets the representations right.

Identification of Potential miRNA-mRNA Regulatory Network in Tetralogy of Fallot: A Network Biology Approach

BackgroundTetralogy of Fallot (ToF) is one of the most prevalent and fatal birth defects. Its pathogenesis remains unknown and it’s not easily diagnosed at early stage. Therefore, it’s necessary to explore the critical regulators and molecular mechanism in ToF to find out novel molecular markers for early diagnosis.MethodsThree ToF datasets (GSE35490, GSE40128, GSE36761) were downloaded from the GEO database. The differentially expressed microRNAs (DEMs) and mRNAs (DEGs) were identified between ToF infants and normal infants after data preprocessing, followed by GO and KEGG analysis of DEGs. Then, PPI network and modular analysis were performed to identify the hub genes. Ultimately, potential miRNA-mRNA pathways in ToF were constructed based on the integrated data.Results22 overlapping DEMs were found in the GES35490 and GSE40128. Simultaneous, 181 intersected genes were found and identified as the significant DEGs including 84 down-regulated DEGs and 97 up-regulated DEGs. Further, 20 hub genes ranked by top 10% with high connectivity, including STAT3, FBN1, RUNX2, were found by PPT network and modular analysis. Furthermore, GO and KEGG analysis showed these DEGs were linked to cell cycle, apoptotic process, transcription activity and FOX signaling pathway. Additionally, we establish three potential miRNA-mRNA pathway, including miR-22-STAT3, miR-336/miR486-FBN1, miR-222-RUNX2, which can participate in the formation of ToF by cell cycle and transcription activity.ConclusionsThree miRNA-mRNA pathways were established and indicated cell cycle and transcription activity may be involved in the pathogenesis of ToF. Our study provided a novel bio-marker for early diagnosis of ToF.

Methodological issues of metrological analysis of planned medieval towns and villages

<p class="Abstract">In this paper, we illustrate problems related to the application of two methods used for the reconstruction of the parcellation of medieval towns: modular analysis and the cosine quantogram. We propose the usage of the cosine quantogram, which is rarely used to study urban layout, for the identification of units of measurement in regular medieval towns. Based on two examples from the region of Silesia, Poland, Namyslów and Dzierzoniów, we discuss the usefulness of both methods in the reconstruction of the original measuring system and town layout. For the first time, we have applied these two methods to the study of the layout of a regular village. Despite the limitations, such as the level of precision in the construction of a medieval town’s layout at the time of its foundation, later changes to the division of plots and the known inaccuracy of modern maps, it seems that combining both methods allows the determination of the module used for the planning of the original urban layout. The application of the cosine quantogram can be useful for improving the results of modular analysis. Nevertheless, the results of both methods should be verified against archaeological results and historical research.</p>

Environmental aspects of insect mass production

Mass production of insects is calling for environmentally optimised and economically efficient insect value chains. It is a complex task considering a great variety in insect species, production scales, feed formulations, etc. Taking a challenge of environmental impact clarification, a few studies highlight on life cycle assessment (LCA) of insect production. The current study is aimed to systemise 24 selected previous studies to establish a modular framework for the determination of contribution of sustainability assessment factors of insect production chains. Reviewing published studies according to the elements of LCA, the study identified a feasible approach for the modelling of insect production chains, which can be used for the facilitation of comparability of further LCA studies. The approach is based on a modular analysis of insect production through a graphical mapping of value chains (allowed identification of precise system boundaries) supplemented with table analysis considering scale of production, reference (functional) unit, impact assessment methodology and type of LCA. Such an approach allows for consistency in LCA setting and further comparability of results.