Body part categorical matching in chimpanzees (Pan troglodytes).

Humans categorize body parts, reflecting our knowledge about bodies, and this could be useful in higher-level activities involving bodies. We tested whether humans' closest living relatives-chimpanzees-have the same ability using touchscreen tasks, focusing on the major parts: heads, torsos, arms, and legs. Six chimpanzees were trained to perform a body part matching-to-sample task using sets of pictures of chimpanzee bodies, where in each trial, the sample and choice pictures were the same. Five passed the training and received the test sessions, where three trial types were mixed: trained same-individual picture pairs; novel same-individual picture pairs; and novel different-individual picture pairs. All participants performed better than the chance level in all conditions and for all body parts. Further analyses showed differences in performance when the samples were different body parts. For example, the results revealed better performances for heads and torsos than arms and legs in "novel different-individual pairs". The study showed that chimpanzees can visually match and categorize body parts in this experiment setting, even across different chimpanzees' bodies, suggesting potential biological understanding. Different performances for body parts suggested a deviated categorization from humans. We hope this study will inspire future research on the evolution of body perception.

A Graph Representation Approach Based on Light Gradient Boosting Machine for Predicting Drug-Disease Associations.

Determining the association between drug and disease is important in drug development. However, existing approaches for drug-disease associations (DDAs) prediction are too homogeneous in terms of feature extraction. Here, a novel graph representation approach based on light gradient boosting machine (GRLGB) is proposed for prediction of DDAs. After the introduction of the protein into a heterogeneous network, nodes features were extracted from two perspectives: network topology and biological knowledge. Finally, the GRLGB classifier was applied to predict potential DDAs. GRLGB achieved satisfactory results on Bdataset and Fdataset through 10-fold cross-validation. To further prove the reliability of the GRLGB, case studies involving anxiety disorders and clozapine were conducted. The results suggest that GRLGB can identify novel DDAs.

PriPath: identifying dysregulated pathways from differential gene expression via grouping, scoring, and modeling with an embedded feature selection approach.

BACKGROUND: Cell homeostasis relies on the concerted actions of genes, and dysregulated genes can lead to diseases. In living organisms, genes or their products do not act alone but within networks. Subsets of these networks can be viewed as modules that provide specific functionality to an organism. The Kyoto encyclopedia of genes and genomes (KEGG) systematically analyzes gene functions, proteins, and molecules and combines them into pathways. Measurements of gene expression (e.g., RNA-seq data) can be mapped to KEGG pathways to determine which modules are affected or dysregulated in the disease. However, genes acting in multiple pathways and other inherent issues complicate such analyses. Many current approaches may only employ gene expression data and need to pay more attention to some of the existing knowledge stored in KEGG pathways for detecting dysregulated pathways. New methods that consider more precompiled information are required for a more holistic association between gene expression and diseases. RESULTS: PriPath is a novel approach that transfers the generic process of grouping and scoring, followed by modeling to analyze gene expression with KEGG pathways. In PriPath, KEGG pathways are utilized as the grouping function as part of a machine learning algorithm for selecting the most significant KEGG pathways. A machine learning model is trained to differentiate between diseases and controls using those groups. We have tested PriPath on 13 gene expression datasets of various cancers and other diseases. Our proposed approach successfully assigned biologically and clinically relevant KEGG terms to the samples based on the differentially expressed genes. We have comparatively evaluated the performance of PriPath against other tools, which are similar in their merit. For each dataset, we manually confirmed the top results of PriPath in the literature and found that most predictions can be supported by previous experimental research. CONCLUSIONS: PriPath can thus aid in determining dysregulated pathways, which applies to medical diagnostics. In the future, we aim to advance this approach so that it can perform patient stratification based on gene expression and identify druggable targets. Thereby, we cover two aspects of precision medicine.

In silico protein function prediction: the rise of machine learning-based approaches.

Proteins function as integral actors in essential life processes, rendering the realm of protein research a fundamental domain that possesses the potential to propel advancements in pharmaceuticals and disease investigation. Within the context of protein research, an imperious demand arises to uncover protein functionalities and untangle intricate mechanistic underpinnings. Due to the exorbitant costs and limited throughput inherent in experimental investigations, computational models offer a promising alternative to accelerate protein function annotation. In recent years, protein pre-training models have exhibited noteworthy advancement across multiple prediction tasks. This advancement highlights a notable prospect for effectively tackling the intricate downstream task associated with protein function prediction. In this review, we elucidate the historical evolution and research paradigms of computational methods for predicting protein function. Subsequently, we summarize the progress in protein and molecule representation as well as feature extraction techniques. Furthermore, we assess the performance of machine learning-based algorithms across various objectives in protein function prediction, thereby offering a comprehensive perspective on the progress within this field.

clusterProfiler 4.0: A universal enrichment tool for interpreting omics data.

Functional enrichment analysis is pivotal for interpreting high-throughput omics data in life science. It is crucial for this type of tool to use the latest annotation databases for as many organisms as possible. To meet these requirements, we present here an updated version of our popular Bioconductor package, clusterProfiler 4.0. This package has been enhanced considerably compared with its original version published 9 years ago. The new version provides a universal interface for functional enrichment analysis in thousands of organisms based on internally supported ontologies and pathways as well as annotation data provided by users or derived from online databases. It also extends the dplyr and ggplot2 packages to offer tidy interfaces for data operation and visualization. Other new features include gene set enrichment analysis and comparison of enrichment results from multiple gene lists. We anticipate that clusterProfiler 4.0 will be applied to a wide range of scenarios across diverse organisms.

Leveraging Structured Biological Knowledge for Counterfactual Inference: A Case Study of Viral Pathogenesis.

Counterfactual inference is a useful tool for comparing outcomes of interventions on complex systems. It requires us to represent the system in form of a structural causal model, complete with a causal diagram, probabilistic assumptions on exogenous variables, and functional assignments. Specifying such models can be extremely difficult in practice. The process requires substantial domain expertise, and does not scale easily to large systems, multiple systems, or novel system modifications. At the same time, many application domains, such as molecular biology, are rich in structured causal knowledge that is qualitative in nature. This article proposes a general approach for querying a causal biological knowledge graph, and converting the qualitative result into a quantitative structural causal model that can learn from data to answer the question. We demonstrate the feasibility, accuracy and versatility of this approach using two case studies in systems biology. The first demonstrates the appropriateness of the underlying assumptions and the accuracy of the results. The second demonstrates the versatility of the approach by querying a knowledge base for the molecular determinants of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm, and performing counterfactual inference to estimate the causal effect of medical countermeasures for severely ill patients.

The friendly fossa: The effect of anthropomorphic language on learning about unfamiliar animals through both storybooks and live animal experiences.

Children's storybooks about animals often use elements of fantasy; even educational storybooks intended to teach children about factual and biological properties include talking animals depicted as more like humans than animals. Previous research has found that anthropomorphic images, specifically in storybooks, hinder factual learning and thus should not be used in the context of educational experiences. However, little research has explored the impact of anthropomorphic language alone as well as its use in other contexts such as zoos where parents often naturally use anthropomorphic language. The current studies explored the impact of anthropomorphic language on learning about an unfamiliar animal (fossa) across two contexts: storybooks (Study 1; N = 48; age range = 4;0-6;3 [years; months]) and a zoo (Study 2a; N = 29; age range = 4;5-7;10). An adult comparison group (Study 2b, N = 82) was also included. Across both studies, there was no evidence that anthropomorphic language decreased factual learning. However, children given anthropomorphic information about a fossa were more likely to generalize anthropomorphic traits, such as emotions, intentions, and preferences, to other fossas, and this was consistent with the adult comparison group. We discuss considerations for parents and educators regarding the appropriateness of fantastical language about animals in experiences specifically designed to support biological learning.

Application of Biological Domain Knowledge Based Feature Selection on Gene Expression Data.

In the last two decades, there have been massive advancements in high throughput technologies, which resulted in the exponential growth of public repositories of gene expression datasets for various phenotypes. It is possible to unravel biomarkers by comparing the gene expression levels under different conditions, such as disease vs. control, treated vs. not treated, drug A vs. drug B, etc. This problem refers to a well-studied problem in the machine learning domain, i.e., the feature selection problem. In biological data analysis, most of the computational feature selection methodologies were taken from other fields, without considering the nature of the biological data. Thus, integrative approaches that utilize the biological knowledge while performing feature selection are necessary for this kind of data. The main idea behind the integrative gene selection process is to generate a ranked list of genes considering both the statistical metrics that are applied to the gene expression data, and the biological background information which is provided as external datasets. One of the main goals of this review is to explore the existing methods that integrate different types of information in order to improve the identification of the biomolecular signatures of diseases and the discovery of new potential targets for treatment. These integrative approaches are expected to aid the prediction, diagnosis, and treatment of diseases, as well as to enlighten us on disease state dynamics, mechanisms of their onset and progression. The integration of various types of biological information will necessitate the development of novel techniques for integration and data analysis. Another aim of this review is to boost the bioinformatics community to develop new approaches for searching and determining significant groups/clusters of features based on one or more biological grouping functions.

DynOVis: a web tool to study dynamic perturbations for capturing dose-over-time effects in biological networks.

BACKGROUND: The development of high throughput sequencing techniques provides us with the possibilities to obtain large data sets, which capture the effect of dynamic perturbations on cellular processes. However, because of the dynamic nature of these processes, the analysis of the results is challenging. Therefore, there is a great need for bioinformatics tools that address this problem. RESULTS: Here we present DynOVis, a network visualization tool that can capture dynamic dose-over-time effects in biological networks. DynOVis is an integrated work frame of R packages and JavaScript libraries and offers a force-directed graph network style, involving multiple network analysis methods such as degree threshold, but more importantly, it allows for node expression animations as well as a frame-by-frame view of the dynamic exposure. Valuable biological information can be highlighted on the nodes in the network, by the integration of various databases within DynOVis. This information includes pathway-to-gene associations from ConsensusPathDB, disease-to-gene associations from the Comparative Toxicogenomics databases, as well as Entrez gene ID, gene symbol, gene synonyms and gene type from the NCBI database. CONCLUSIONS: DynOVis could be a useful tool to analyse biological networks which have a dynamic nature. It can visualize the dynamic perturbations in biological networks and allows the user to investigate the changes over time. The integrated data from various online databases makes it easy to identify the biological relevance of nodes in the network. With DynOVis we offer a service that is easy to use and does not require any bioinformatics skills to visualize a network.

CODA-ML: context-specific biological knowledge representation for systemic physiology analysis.

BACKGROUND: Computational analysis of complex diseases involving multiple organs requires the integration of multiple different models into a unified model. Different models are often constructed in heterogeneous formats. Thus, the integration of the models requires a standard language format that can effectively represent essential biological information. However, the previously introduced formats have limitations that prevent from adequately representing essential biological information, particularly specifications of bio-molecules and biological contexts. RESULTS: We defined an XML-based markup language called context-oriented directed association markup language (CODA-ML), which better represents essential biological information. The CODA-ML has two major strengths in designating molecular specifications and biological contexts. It can cover heterogeneous entity types involved in biological events (e.g. gene/protein, compound, cellular function, disease). Molecular types of entities can have molecular specifications which include detailed information of a molecule from isoforms to modifications, enabling high-resolution representation of molecules. In addition, it can distinguish biological events that vary depending on different biological contexts such as cell types or disease conditions. Especially representation of inter-cellular events as well as intra-cellular events is available. These two major strengths can resolve contradictory associations when different models are integrated into one unified model, which improves the accuracy of the model. CONCLUSIONS: With the CODA-ML, diverse models such as signaling pathways, metabolic pathways, and gene regulatory pathways can be represented in a unified language format. Heterogeneous entity types can be covered by the CODA-ML, thus it enables detailed description for the mechanisms of diseases or drugs from multiple perspectives (e.g., molecule, function or disease). The CODA-ML is expected to help integrate different models into one systemic model in an efficient and effective. The unified model can be used to perform computational analysis not only for cancer but also for other complex diseases involving multiple organs beyond a single cell.

BLASSO: integration of biological knowledge into a regularized linear model.

BACKGROUND: In RNA-Seq gene expression analysis, a genetic signature or biomarker is defined as a subset of genes that is probably involved in a given complex human trait and usually provide predictive capabilities for that trait. The discovery of new genetic signatures is challenging, as it entails the analysis of complex-nature information encoded at gene level. Moreover, biomarkers selection becomes unstable, since high correlation among the thousands of genes included in each sample usually exists, thus obtaining very low overlapping rates between the genetic signatures proposed by different authors. In this sense, this paper proposes BLASSO, a simple and highly interpretable linear model with l1-regularization that incorporates prior biological knowledge to the prediction of breast cancer outcomes. Two different approaches to integrate biological knowledge in BLASSO, Gene-specific and Gene-disease, are proposed to test their predictive performance and biomarker stability on a public RNA-Seq gene expression dataset for breast cancer. The relevance of the genetic signature for the model is inspected by a functional analysis. RESULTS: BLASSO has been compared with a baseline LASSO model. Using 10-fold cross-validation with 100 repetitions for models' assessment, average AUC values of 0.7 and 0.69 were obtained for the Gene-specific and the Gene-disease approaches, respectively. These efficacy rates outperform the average AUC of 0.65 obtained with the LASSO. With respect to the stability of the genetic signatures found, BLASSO outperformed the baseline model in terms of the robustness index (RI). The Gene-specific approach gave RI of 0.15±0.03, compared to RI of 0.09±0.03 given by LASSO, thus being 66% times more robust. The functional analysis performed to the genetic signature obtained with the Gene-disease approach showed a significant presence of genes related with cancer, as well as one gene (IFNK) and one pseudogene (PCNAP1) which a priori had not been described to be related with cancer. CONCLUSIONS: BLASSO has been shown as a good choice both in terms of predictive efficacy and biomarker stability, when compared to other similar approaches. Further functional analyses of the genetic signatures obtained with BLASSO has not only revealed genes with important roles in cancer, but also genes that should play an unknown or collateral role in the studied disease.

A multi-objective gene clustering algorithm guided by apriori biological knowledge with intensification and diversification strategies.

BACKGROUND: Biologists aim to understand the genetic background of diseases, metabolic disorders or any other genetic condition. Microarrays are one of the main high-throughput technologies for collecting information about the behaviour of genetic information on different conditions. In order to analyse this data, clustering arises as one of the main techniques used, and it aims at finding groups of genes that have some criterion in common, like similar expression profile. However, the problem of finding groups is normally multi dimensional, making necessary to approach the clustering as a multi-objective problem where various cluster validity indexes are simultaneously optimised. They are usually based on criteria like compactness and separation, which may not be sufficient since they can not guarantee the generation of clusters that have both similar expression patterns and biological coherence. METHOD: We propose a Multi-Objective Clustering algorithm Guided by a-Priori Biological Knowledge (MOC-GaPBK) to find clusters of genes with high levels of co-expression, biological coherence, and also good compactness and separation. Cluster quality indexes are used to optimise simultaneously gene relationships at expression level and biological functionality. Our proposal also includes intensification and diversification strategies to improve the search process. RESULTS: The effectiveness of the proposed algorithm is demonstrated on four publicly available datasets. Comparative studies of the use of different objective functions and other widely used microarray clustering techniques are reported. Statistical, visual and biological significance tests are carried out to show the superiority of the proposed algorithm. CONCLUSIONS: Integrating a-priori biological knowledge into a multi-objective approach and using intensification and diversification strategies allow the proposed algorithm to find solutions with higher quality than other microarray clustering techniques available in the literature in terms of co-expression, biological coherence, compactness and separation.

Towards FAIRer Biological Knowledge Networks Using a Hybrid Linked Data and Graph Database Approach.

The speed and accuracy of new scientific discoveries - be it by humans or artificial intelligence - depends on the quality of the underlying data and on the technology to connect, search and share the data efficiently. In recent years, we have seen the rise of graph databases and semi-formal data models such as knowledge graphs to facilitate software approaches to scientific discovery. These approaches extend work based on formalised models, such as the Semantic Web. In this paper, we present our developments to connect, search and share data about genome-scale knowledge networks (GSKN). We have developed a simple application ontology based on OWL/RDF with mappings to standard schemas. We are employing the ontology to power data access services like resolvable URIs, SPARQL endpoints, JSON-LD web APIs and Neo4j-based knowledge graphs. We demonstrate how the proposed ontology and graph databases considerably improve search and access to interoperable and reusable biological knowledge (i.e. the FAIRness data principles).

A method combining a random forest-based technique with the modeling of linkage disequilibrium through latent variables, to run multilocus genome-wide association studies.

BACKGROUND: Genome-wide association studies (GWASs) have been widely used to discover the genetic basis of complex phenotypes. However, standard single-SNP GWASs suffer from lack of power. In particular, they do not directly account for linkage disequilibrium, that is the dependences between SNPs (Single Nucleotide Polymorphisms). RESULTS: We present the comparative study of two multilocus GWAS strategies, in the random forest-based framework. The first method, T-Trees, was designed by Botta and collaborators (Botta et al., PLoS ONE 9(4):e93379, 2014). We designed the other method, which is an innovative hybrid method combining T-Trees with the modeling of linkage disequilibrium. Linkage disequilibrium is modeled through a collection of tree-shaped Bayesian networks with latent variables, following our former works (Mourad et al., BMC Bioinformatics 12(1):16, 2011). We compared the two methods, both on simulated and real data. For dominant and additive genetic models, in either of the conditions simulated, the hybrid approach always slightly performs better than T-Trees. We assessed predictive powers through the standard ROC technique on 14 real datasets. For 10 of the 14 datasets analyzed, the already high predicted power observed for T-Trees (0.910-0.946) can still be increased by up to 0.030. We also assessed whether the distributions of SNPs' scores obtained from T-Trees and the hybrid approach differed. Finally, we thoroughly analyzed the intersections of top 100 SNPs output by any two or the three methods amongst T-Trees, the hybrid approach, and the single-SNP method. CONCLUSIONS: The sophistication of T-Trees through finer linkage disequilibrium modeling is shown beneficial. The distributions of SNPs' scores generated by T-Trees and the hybrid approach are shown statistically different, which suggests complementary of the methods. In particular, for 12 of the 14 real datasets, the distribution tail of highest SNPs' scores shows larger values for the hybrid approach. Thus are pinpointed more interesting SNPs than by T-Trees, to be provided as a short list of prioritized SNPs, for a further analysis by biologists. Finally, among the 211 top 100 SNPs jointly detected by the single-SNP method, T-Trees and the hybrid approach over the 14 datasets, we identified 72 and 38 SNPs respectively present in the top25s and top10s for each method.

Methods to analyze big data in pharmacogenomics research.

The scale and scope of pharmacogenomics research continues to expand as the cost and efficiency of molecular data generation techniques advance. These new technologies give rise to enormous opportunity for the identification of important genetic and genomic factors important for drug treatment response. With this opportunity come significant challenges. Most of these can be categorized as 'big data' issues, facing not only pharmacogenomics, but other fields in the life sciences as well. In this review, we describe some of the analysis techniques and tools being implemented for genetic/genomic discovery in pharmacogenomics.

Incorporating prior biological knowledge for network-based differential gene expression analysis using differentially weighted graphical LASSO.

BACKGROUND: Conventional differential gene expression analysis by methods such as student's t-test, SAM, and Empirical Bayes often searches for statistically significant genes without considering the interactions among them. Network-based approaches provide a natural way to study these interactions and to investigate the rewiring interactions in disease versus control groups. In this paper, we apply weighted graphical LASSO (wgLASSO) algorithm to integrate a data-driven network model with prior biological knowledge (i.e., protein-protein interactions) for biological network inference. We propose a novel differentially weighted graphical LASSO (dwgLASSO) algorithm that builds group-specific networks and perform network-based differential gene expression analysis to select biomarker candidates by considering their topological differences between the groups. RESULTS: Through simulation, we showed that wgLASSO can achieve better performance in building biologically relevant networks than purely data-driven models (e.g., neighbor selection, graphical LASSO), even when only a moderate level of information is available as prior biological knowledge. We evaluated the performance of dwgLASSO for survival time prediction using two microarray breast cancer datasets previously reported by Bild et al. and van de Vijver et al. Compared with the top 10 significant genes selected by conventional differential gene expression analysis method, the top 10 significant genes selected by dwgLASSO in the dataset from Bild et al. led to a significantly improved survival time prediction in the independent dataset from van de Vijver et al. Among the 10 genes selected by dwgLASSO, UBE2S, SALL2, XBP1 and KIAA0922 have been confirmed by literature survey to be highly relevant in breast cancer biomarker discovery study. Additionally, we tested dwgLASSO on TCGA RNA-seq data acquired from patients with hepatocellular carcinoma (HCC) on tumors samples and their corresponding non-tumorous liver tissues. Improved sensitivity, specificity and area under curve (AUC) were observed when comparing dwgLASSO with conventional differential gene expression analysis method. CONCLUSIONS: The proposed network-based differential gene expression analysis algorithm dwgLASSO can achieve better performance than conventional differential gene expression analysis methods by integrating information at both gene expression and network topology levels. The incorporation of prior biological knowledge can lead to the identification of biologically meaningful genes in cancer biomarker studies.

MEvoLib v1.0: the first molecular evolution library for Python.

BACKGROUND: Molecular evolution studies involve many different hard computational problems solved, in most cases, with heuristic algorithms that provide a nearly optimal solution. Hence, diverse software tools exist for the different stages involved in a molecular evolution workflow. RESULTS: We present MEvoLib, the first molecular evolution library for Python, providing a framework to work with different tools and methods involved in the common tasks of molecular evolution workflows. In contrast with already existing bioinformatics libraries, MEvoLib is focused on the stages involved in molecular evolution studies, enclosing the set of tools with a common purpose in a single high-level interface with fast access to their frequent parameterizations. The gene clustering from partial or complete sequences has been improved with a new method that integrates accessible external information (e.g. GenBank's features data). Moreover, MEvoLib adjusts the fetching process from NCBI databases to optimize the download bandwidth usage. In addition, it has been implemented using parallelization techniques to cope with even large-case scenarios. CONCLUSIONS: MEvoLib is the first library for Python designed to facilitate molecular evolution researches both for expert and novel users. Its unique interface for each common task comprises several tools with their most used parameterizations. It has also included a method to take advantage of biological knowledge to improve the gene partition of sequence datasets. Additionally, its implementation incorporates parallelization techniques to enhance computational costs when handling very large input datasets.

Functional networks inference from rule-based machine learning models.

BACKGROUND: Functional networks play an important role in the analysis of biological processes and systems. The inference of these networks from high-throughput (-omics) data is an area of intense research. So far, the similarity-based inference paradigm (e.g. gene co-expression) has been the most popular approach. It assumes a functional relationship between genes which are expressed at similar levels across different samples. An alternative to this paradigm is the inference of relationships from the structure of machine learning models. These models are able to capture complex relationships between variables, that often are different/complementary to the similarity-based methods. RESULTS: We propose a protocol to infer functional networks from machine learning models, called FuNeL. It assumes, that genes used together within a rule-based machine learning model to classify the samples, might also be functionally related at a biological level. The protocol is first tested on synthetic datasets and then evaluated on a test suite of 8 real-world datasets related to human cancer. The networks inferred from the real-world data are compared against gene co-expression networks of equal size, generated with 3 different methods. The comparison is performed from two different points of view. We analyse the enriched biological terms in the set of network nodes and the relationships between known disease-associated genes in a context of the network topology. The comparison confirms both the biological relevance and the complementary character of the knowledge captured by the FuNeL networks in relation to similarity-based methods and demonstrates its potential to identify known disease associations as core elements of the network. Finally, using a prostate cancer dataset as a case study, we confirm that the biological knowledge captured by our method is relevant to the disease and consistent with the specialised literature and with an independent dataset not used in the inference process. AVAILABILITY: The implementation of our network inference protocol is available at: http://ico2s.org/software/funel.html.

A pedagogical walkthrough of computational modeling and simulation of Wnt signaling pathway using static causal models in MATLAB.

Simulation study in systems biology involving computational experiments dealing with Wnt signaling pathways abound in literature but often lack a pedagogical perspective that might ease the understanding of beginner students and researchers in transition, who intend to work on the modeling of the pathway. This paucity might happen due to restrictive business policies which enforce an unwanted embargo on the sharing of important scientific knowledge. A tutorial introduction to computational modeling of Wnt signaling pathway in a human colorectal cancer dataset using static Bayesian network models is provided. The walkthrough might aid biologists/informaticians in understanding the design of computational experiments that is interleaved with exposition of the Matlab code and causal models from Bayesian network toolbox. The manuscript elucidates the coding contents of the advance article by Sinha (Integr. Biol. 6:1034-1048, 2014) and takes the reader in a step-by-step process of how (a) the collection and the transformation of the available biological information from literature is done, (b) the integration of the heterogeneous data and prior biological knowledge in the network is achieved, (c) the simulation study is designed, (d) the hypothesis regarding a biological phenomena is transformed into computational framework, and (e) results and inferences drawn using d-connectivity/separability are reported. The manuscript finally ends with a programming assignment to help the readers get hands-on experience of a perturbation project. Description of Matlab files is made available under GNU GPL v3 license at the Google code project on https://code.google.com/p/static-bn-for-wnt-signaling-pathway and https: //sites.google.com/site/shriprakashsinha/shriprakashsinha/projects/static-bn-for-wnt-signaling-pathway. Latest updates can be found in the latter website.

Teaching and learning in the Biosciences: the development of an educational programme to assist student nurses in their assessment and management of patients with wounds.

AIMS AND OBJECTIVES: The aim of this project was to develop an educational package for undergraduate student nurses that would provide them with the theoretical knowledge and clinical judgement skills to care for a patient with a wound. BACKGROUND: Internationally there is concern over the adequacy of preparation of undergraduate nurses for the clinical skill of wound care. Deficits have also been identified in the underpinning biological sciences needed for this skill. Expectations associated with wound management have altered significantly in the last two decades with decision making around wound care coming under the scope of practice of nurses. The treatment and care options for patients with wounds must be based on a sound knowledge of how wounds are formed and healed. If nurses do not have the evidence-based knowledge, it can affect wound healing adversely leading to increased patient suffering, pain and delayed healing. From an organisational perspective, delayed healing will increase the cost of care. DESIGN: This project used constructivism learning theory to provide a framework for the development of a wound care educational package for undergraduate Irish nurses in their penultimate year of training. METHODS: Collaboration was formed with key stake holders. Pertinent curriculum content was mapped. Learning strategies to suit the incoming student learning styles were incorporated into newly developed theoretical content and practical skill sessions. CONCLUSION: The developed educational programme will assist student nurses in their care of patients with wounds. RELEVANCE TO CLINICAL PRACTICE: This study provides a model that can be followed to develop small units of the study to keep abreast of changes in health care delivery and the changing scope of practice of nurses. It also contributes to the debate on the teaching and learning of biosciences as it highlights the depth of biological knowledge required as a basis for good evidence-based nursing care.