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Abstract Autism Spectrum Disorder (ASD) is a chronic condition characterised by impairments in social interaction and communication. Early detection of ASD is desired, and there exists a demand for the development of diagnostic aids to facilitate this. A lightweight Involutional Neural Network (INN) architecture has been developed to diagnose ASD. The model follows a simpler architectural design and has less number of parameters than the state‐of‐the‐art (SOTA) image classification models, requiring lower computational resources. The proposed model is trained to detect ASD from eye‐tracking scanpath (SP), heatmap (HM), and fixation map (FM) images. Monte Carlo Dropout has been applied to the model to perform an uncertainty analysis and ensure the effectiveness of the output provided by the proposed INN model. The model has been trained and evaluated using two publicly accessible datasets. From the experiment, it is seen that the model has achieved 98.12% accuracy, 96.83% accuracy, and 97.61% accuracy on SP, FM, and HM, respectively, which outperforms the current SOTA image classification models and other existing works conducted on this topic.

Sleep apnea (SA) is one of the most prevalent sleep-related problems, impacting more than 100 million people worldwide. A full-night Polysomnography (PSG) is an effective SA diagnosis strategy. However, it requires multiple wearable devices and the patient staying overnight to collect the findings, rendering it both a time-consuming and costly option. Research attempts to develop non-invasive, sensor-based, or automated solutions for diagnosing SA are also made in recent years. In this study, we analyzed a total of 85 papers, shortlisted from an initial collection of 954 articles published in reputable scientific repositories, e.g., IEEE Xplore, PubMed Central (PMC), Springer, Elsevier etc., where each chosen study was thoroughly examined to determine its contribution and performance. A detailed analysis of data preprocessing, feature extraction and classification algorithm is also addressed. It is found that most of the studies are based on signal analysis for identifying sleep apnea, which yields results with substantial reliability, while contemporary research emphases have been on heart rate variability and pulse oximetry outcomes.

Stock price prediction is challenging in financial investment, with the AI boom leading to increased interest from researchers. Despite these recent advances, many studies are limited to capturing the time series characteristics of price movement via recurrent neural networks (RNNs) but neglect other critical relevant factors, such as industry, shareholders, and news. On the other hand, graph neural networks have been applied to a broad range of tasks due to their superior performance in capturing complex relations among entities and representation learning. This paper investigates the effectiveness of using graph neural networks for stock price movement prediction. Inspired by a recent study, we capture the complex group-level information (co-movement of similar companies) via hypergraphs. Unlike other hypergraph studies, we also use a graph model to learn pairwise relations. Moreover, we are the first to demonstrate that this simple graph model should be applied before using RNNs, rather than later, as prior research suggested. In this paper, the long-term dependencies of similar companies can be learnt by the next RNNs, which augments their predictability. We also apply adversarial training to capture the stochastic nature of the financial market and enhance the generalisation of the proposed model. Hence, we contribute with a novel ensemble learning framework to predict stock price movement, named MONEY. It is comprised of (a) a Graph Convolution Network (GCN), representing pairwise industry and price information and (b) a hypergraph convolution network for group-oriented information transmission via hyperedges with adversarial training by adding perturbations on inputs before the last prediction layer. Real-world data experiments demonstrate that MONEY significantly outperforms, on average, the state-of-the-art methods and performs particularly well in the bear market.

Abstract Background Not being well controlled by therapy with inhaled corticosteroids and long‐acting β2 agonist bronchodilators is a major concern for severe‐asthma patients. The current treatment option for these patients is the use of biologicals such as anti‐IgE treatment, omalizumab, as an add‐on therapy. Despite the accepted use of omalizumab, patients do not always benefit from it. Therefore, there is a need to identify reliable biomarkers as predictors of omalizumab response. Methods Two novel computational algorithms, machine‐learning based Recursive Ensemble Feature Selection (REFS) and rule‐based algorithm Logic Explainable Networks (LEN), were used on open accessible mRNA expression data from moderate‐to‐severe asthma patients to identify genes as predictors of omalizumab response. Results With REFS, the number of features was reduced from 28,402 genes to 5 genes while obtaining a cross‐validated accuracy of 0.975. The 5 responsiveness predictive genes encode the following proteins: Coiled‐coil domain‐ containing protein 113 (CCDC113), Solute Carrier Family 26 Member 8 (SLC26A), Protein Phosphatase 1 Regulatory Subunit 3D (PPP1R3D), C‐Type lectin Domain Family 4 member C (CLEC4C) and LOC100131780 (not annotated). The LEN algorithm found 4 identical genes with REFS: CCDC113, SLC26A8 PPP1R3D and LOC100131780. Literature research showed that the 4 identified responsiveness predicting genes are associated with mucosal immunity, cell metabolism, and airway remodeling. Conclusion and clinical relevance Both computational methods show 4 identical genes as predictors of omalizumab response in moderate‐to‐severe asthma patients. The obtained high accuracy indicates that our approach has potential in clinical settings. Future studies in relevant cohort data should validate our computational approach.

Predicting fetal brain abnormalities (FBAs) is an urgent global problem, as nearly three of every thousand women are pregnant with neurological abnormalities. Therefore, early detection of FBAs using deep learning (DL) can help to enhance the planning and quality of diagnosis and treatment for pregnant women. Most of the research papers focused on brain abnormalities of newborns and premature infants, but fewer studies concentrated on fetuses. This study proposed a deep learning-CNN-based framework named StackFBAs that utilized the stacking strategy to classify fetus brain abnormalities more accurately using MRI images at an early stage. We considered the Greedy-based Neural architecture search (NAS) method to identify the best CNN architectures to solve this problem utilizing brain MRI images. A total of 94 CNN architectures were generated from the NAS method, and the best 5 CNN models were selected to build the baseline models. Subsequently, the probabilistic scores of these baseline models were combined to construct the final meta-model (KNN) utilizing the stacking strategy. The experimental results demonstrated that StackFBAs outperform pre-trained CNN Models (e.g., VGG16, VGG19, ResNet50, DenseNet121, and ResNet152) with transfer learning (TL) and existing models with the 5-fold cross-validation tests. StackFBAs achieved an overall accuracy of 80%, an F1-score of 78%, 76% sensitivity, and a specificity of 78%. Moreover, we employed the federated learning technique that protects sensitive fetal MRI data, combines results, and finds common patterns from many users, making the model more robust for the privacy and security of user-sensitive data. We believe that our novel framework could be used as a helpful tool for detecting brain abnormalities at an early stage.

Abstract Progesterone receptors (PRs) are implicated in various cancers since their presence/absence can determine clinical outcomes. The overstimulation of progesterone can facilitate oncogenesis and thus, its modulation through PR inhibition is urgently needed. To address this issue, a novel stacked ensemble learning approach (termed StackPR) is presented for fast, accurate, and large-scale identification of PR antagonists using only SMILES notation without the need for 3D structural information. We employed six popular machine learning (ML) algorithms (i.e., logistic regression, partial least squares, k-nearest neighbor, support vector machine, extremely randomized trees, and random forest) coupled with twelve conventional molecular descriptors to create 72 baseline models. Then, a genetic algorithm in conjunction with the self-assessment-report approach was utilized to determine m out of the 72 baseline models as means of developing the final meta-predictor using the stacking strategy and tenfold cross-validation test. Experimental results on the independent test dataset show that StackPR achieved impressive predictive performance with an accuracy of 0.966 and Matthew’s coefficient correlation of 0.925. In addition, analysis based on the SHapley Additive exPlanation algorithm and molecular docking indicates that aliphatic hydrocarbons and nitrogen-containing substructures were the most important features for having PR antagonist activity. Finally, we implemented an online webserver using StackPR, which is freely accessible at http://pmlabstack.pythonanywhere.com/StackPR . StackPR is anticipated to be a powerful computational tool for the large-scale identification of unknown PR antagonist candidates for follow-up experimental validation.

Abstract Amyloid proteins have the ability to form insoluble fibril aggregates that have important pathogenic effects in many tissues. Such amyloidoses are prominently associated with common diseases such as type 2 diabetes, Alzheimer's disease, and Parkinson's disease. There are many types of amyloid proteins, and some proteins that form amyloid aggregates when in a misfolded state. It is difficult to identify such amyloid proteins and their pathogenic properties, but a new and effective approach is by developing effective bioinformatics tools. While several machine learning (ML)-based models for in silico identification of amyloid proteins have been proposed, their predictive performance is limited. In this study, we present AMYPred-FRL, a novel meta-predictor that uses a feature representation learning approach to achieve more accurate amyloid protein identification. AMYPred-FRL combined six well-known ML algorithms (extremely randomized tree, extreme gradient boosting, k-nearest neighbor, logistic regression, random forest, and support vector machine) with ten different sequence-based feature descriptors to generate 60 probabilistic features (PFs), as opposed to state-of-the-art methods developed by a single feature-based approach. A logistic regression recursive feature elimination (LR-RFE) method was used to find the optimal m number of 60 PFs in order to improve the predictive performance. Finally, using the meta-predictor approach, the 20 selected PFs were fed into a logistic regression method to create the final hybrid model (AMYPred-FRL). Both cross-validation and independent tests showed that AMYPred-FRL achieved superior predictive performance than its constituent baseline models. In an extensive independent test, AMYPred-FRL outperformed the existing methods by 5.5% and 16.1%, respectively, with accuracy and MCC of 0.873 and 0.710. To expedite high-throughput prediction, a user-friendly web server of AMYPred-FRL is freely available at http://pmlabstack.pythonanywhere.com/AMYPred-FRL . It is anticipated that AMYPred-FRL will be a useful tool in helping researchers to identify new amyloid proteins.

Abstract Fast and accurate identification of phage virion proteins (PVPs) would greatly aid facilitation of antibacterial drug discovery and development. Although, several research efforts based on machine learning (ML) methods have been made for in silico identification of PVPs, these methods have certain limitations. Therefore, in this study, we propose a new computational approach, termed SCORPION, (StaCking-based Predictior fOR Phage VIrion PrOteiNs), to accurately identify PVPs using only protein primary sequences. Specifically, we explored comprehensive 13 different feature descriptors from different aspects (i.e., compositional information, composition-transition-distribution information, position-specific information and physicochemical properties) with 10 popular ML algorithms to construct a pool of optimal baseline models. These optimal baseline models were then used to generate probabilistic features (PFs) and considered as a new feature vector. Finally, we utilized a two-step feature selection strategy to determine the optimal PF feature vector and used this feature vector to develop a stacked model (SCORPION). Both tenfold cross-validation and independent test results indicate that SCORPION achieves superior predictive performance than its constitute baseline models and existing methods. We anticipate SCORPION will serve as a useful tool for the cost-effective and large-scale screening of new PVPs. The source codes and datasets for this work are available for downloading in the GitHub repository ( https://github.com/saeed344/SCORPION ).

Abstract Machine learning (ML), one aspect of artificial intelligence (AI), involves computer algorithms that train themselves. They have been widely applied in the healthcare domain. However, many trained ML algorithms operate as ‘black boxes’, producing a prediction from input data without a clear explanation of their workings. Non-transparent predictions are of limited utility in many clinical domains, where decisions must be justifiable. Here, we apply class-contrastive counterfactual reasoning to ML to demonstrate how specific changes in inputs lead to different predictions of mortality in people with severe mental illness (SMI), a major public health challenge. We produce predictions accompanied by visual and textual explanations as to how the prediction would have differed given specific changes to the input. We apply it to routinely collected data from a mental health secondary care provider in patients with schizophrenia. Using a data structuring framework informed by clinical knowledge, we captured information on physical health, mental health, and social predisposing factors. We then trained an ML algorithm and other statistical learning techniques to predict the risk of death. The ML algorithm predicted mortality with an area under receiver operating characteristic curve (AUROC) of 0.80 (95% confidence intervals [0.78, 0.82]). We used class-contrastive analysis to produce explanations for the model predictions. We outline the scenarios in which class-contrastive analysis is likely to be successful in producing explanations for model predictions. Our aim is not to advocate for a particular model but show an application of the class-contrastive analysis technique to electronic healthcare record data for a disease of public health significance. In patients with schizophrenia, our work suggests that use or prescription of medications like antidepressants was associated with lower risk of death. Abuse of alcohol/drugs and a diagnosis of delirium were associated with higher risk of death. Our ML models highlight the role of co-morbidities in determining mortality in patients with schizophrenia and the need to manage co-morbidities in these patients. We hope that some of these bio-social factors can be targeted therapeutically by either patient-level or service-level interventions. Our approach combines clinical knowledge, health data, and statistical learning, to make predictions interpretable to clinicians using class-contrastive reasoning. This is a step towards interpretable AI in the management of patients with schizophrenia and potentially other diseases.

Summary: Discovery of potential drugs requires rapid and precise identification of drug targets. Although traditional experimental methodologies can accurately identify drug targets, they are time-consuming and inappropriate for high-throughput screening. Computational approaches based on machine learning (ML) algorithms can expedite the prediction of druggable proteins; however, the performance of the existing computational methods remains unsatisfactory. This study proposes a computational tool, SPIDER, to enhance the accurate prediction of druggable proteins. SPIDER employs various feature descriptors pertaining to several aspects, including physicochemical properties, compositional information, and composition-transition-distribution information, coupled with well-known ML algorithms to facilitate the construction of the final meta-predictor. The experimental results showed that SPIDER enabled more precise and robust prediction of druggable proteins than the baseline models and current existing methods in terms of the independent test dataset. An online web server was established and made freely available online.

Recently, electroencephalogram-based emotion recognition has become crucial in enabling the Human-Computer Interaction (HCI) system to become more intelligent. Due to the outstanding applications of emotion recognition, e.g., person-based decision making, mind-machine interfacing, cognitive interaction, affect detection, feeling detection, etc., emotion recognition has become successful in attracting the recent hype of AI-empowered research. Therefore, numerous studies have been conducted driven by a range of approaches, which demand a systematic review of methodologies used for this task with their feature sets and techniques. It will facilitate the beginners as guidance towards composing an effective emotion recognition system. In this article, we have conducted a rigorous review on the state-of-the-art emotion recognition systems, published in recent literature, and summarized some of the common emotion recognition steps with relevant definitions, theories, and analyses to provide key knowledge to develop a proper framework. Moreover, studies included here were dichotomized based on two categories: i) deep learning-based, and ii) shallow machine learning-based emotion recognition systems. The reviewed systems were compared based on methods, classifier, the number of classified emotions, accuracy, and dataset used. An informative comparison, recent research trends, and some recommendations are also provided for future research directions.

Topic detection technology can automatically discover new topics on the Internet. This paper investigates domain-oriented feature extraction methods, and proposes a keyword feature extraction method ITFIDF-LP, a subject word feature extraction method LDA-SLP and a topic clustering model based on vector product similarity. A novel Domain-oriented Topic Discovery based on Features Extraction and Topic Clustering (DTD-FETC) model is proposed to analyze open source web of a domain and identify emerging topics in the domain in real time. This article describes a DTD-FETC system built for cyber security domain. It filters and aggregates web for specical security threat topics such as vulnerability and malware, and helps security staff respond quickly and defends against the emerging cyber threats as early as possible. The recall rate, accuracy and F1 value results of the DTD-FETC method applied to the cyber security dataset are all above 0.99.

In the traditional cloud architecture, data needs to be uploaded to the cloud for processing, bringing delays in transmission and response. Edge network emerges as the times require. Data processing on the edge nodes can reduce the delay of data transmission and improve the response speed. In recent years, the need for artificial intelligence of edge network has been proposed. However, the data of a single, individual edge node is limited and does not satisfy the conditions of machine learning. Therefore, performing edge network machine learning under the premise of data confidentiality became a research hotspot. This paper proposes a Privacy-Preserving Asynchronous Federated Learning Mechanism for Edge Network Computing (PAFLM), which can allow multiple edge nodes to achieve more efficient federated learning without sharing their private data. Compared with the traditional distributed learning, the proposed method compresses the communications between nodes and parameter server during the training process without affecting the accuracy. Moreover, it allows the node to join or quit in any process of learning, which can be suitable to the scene with highly mobile edge devices.

Abstract Background Breast cancer is one of the most common diseases in women worldwide. Many studies have been conducted to predict the survival indicators, however most of these analyses were predominantly performed using basic statistical methods. As an alternative, this study used machine learning techniques to build models for detecting and visualising significant prognostic indicators of breast cancer survival rate. Methods A large hospital-based breast cancer dataset retrieved from the University Malaya Medical Centre, Kuala Lumpur, Malaysia (n = 8066) with diagnosis information between 1993 and 2016 was used in this study. The dataset contained 23 predictor variables and one dependent variable, which referred to the survival status of the patients (alive or dead). In determining the significant prognostic factors of breast cancer survival rate, prediction models were built using decision tree, random forest, neural networks, extreme boost, logistic regression, and support vector machine. Next, the dataset was clustered based on the receptor status of breast cancer patients identified via immunohistochemistry to perform advanced modelling using random forest. Subsequently, the important variables were ranked via variable selection methods in random forest. Finally, decision trees were built and validation was performed using survival analysis. Results In terms of both model accuracy and calibration measure, all algorithms produced close outcomes, with the lowest obtained from decision tree (accuracy = 79.8%) and the highest from random forest (accuracy = 82.7%). The important variables identified in this study were cancer stage classification, tumour size, number of total axillary lymph nodes removed, number of positive lymph nodes, types of primary treatment, and methods of diagnosis. Conclusion Interestingly the various machine learning algorithms used in this study yielded close accuracy hence these methods could be used as alternative predictive tools in the breast cancer survival studies, particularly in the Asian region. The important prognostic factors influencing survival rate of breast cancer identified in this study, which were validated by survival curves, are useful and could be translated into decision support tools in the medical domain.

Almost all recent deep reinforcement learning algorithms use four consecutive frames as the state space to retain the dynamic information. If the training state data constitute an image, the state space is used as the input of the neural network for training. As an AI-assisted decision-making technology, a dynamic influence map can describe dynamic information. In this paper, we propose the use of a frame image superimposed with an influence map as the state space to express dynamic information. Herein, we optimize Ape-x as a distributed reinforcement learning algorithm. Sparse reward is an issue that must be solved in refined intelligent decision making. The use of an influence map is proposed to generate the intrinsic reward when there is no external reward. The experiments conducted in this study prove that the combination of a dynamic influence map and deep reinforcement learning is effective. Compared with the traditional method that uses four consecutive frames to represent dynamic information, the score of the proposed method is increased by 11–13%, the training speed is increased by 59%, the video memory consumption is reduced by 30%, and the memory consumption is reduced by 50%. The proposed method is compared with the Ape-x algorithm without an influence map, DQN, N-Step DQN, QR-DQN, Dueling DQN, and C51. The experimental results show that the final score of the proposed method is higher than that of the compared baseline methods. In addition, the influence map is used to generate an intrinsic reward to effectively resolve the sparse reward problem.

The practice of medical decision making is changing rapidly with the development of innovative computing technologies. The growing interest of data analysis with improvements in big data computer processing methods raises the question of whether machine learning can be integrated with conventional statistics in health research. To help address this knowledge gap, this paper presents a review on the conceptual integration between conventional statistics and machine learning, focusing on the health research. The similarities and differences between the two are compared using mathematical concepts and algorithms. The comparison between conventional statistics and machine learning methods indicates that conventional statistics are the fundamental basis of machine learning, where the black box algorithms are derived from basic mathematics, but are advanced in terms of automated analysis, handling big data and providing interactive visualizations. While the nature of both these methods are different, they are conceptually similar. Based on our review, we conclude that conventional statistics and machine learning are best to be integrated to develop automated data analysis tools. We also strongly believe that machine learning could be explored by health researchers to enhance conventional statistics in decision making for added reliable validation measures.

Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disabilities that are not curable but may be ameliorated by early interventions. We gathered early-detected ASD datasets relating to toddlers, children, adolescents and adults, and applied several feature transformation methods, including log, Z-score and sine functions to these datasets. Various classification techniques were then implemented with these transformed ASD datasets and assessed for their performance. We found SVM showed the best performance for the toddler dataset, while Adaboost gave the best results for the children dataset, Glmboost for the adolescent and Adaboost for the adult datasets. The feature transformations resulting in the best classifications was sine function for toddler and Z-score for children and adolescent datasets. After these analyses, several feature selection techniques were used with these Z-score-transformed datasets to identify the significant ASD risk factors for the toddler, child, adolescent and adult subjects. The results of these analytical approaches indicate that, when appropriately optimised, machine learning methods can provide good predictions of ASD status. This suggests that it may possible to apply these models for the detection of ASD in its early stages.

Neurodegenerative diseases such as Alzheimer's and Parkinson's impact millions of people worldwide. Early diagnosis has proven to greatly increase the chances of slowing down the diseases' progression. Correct diagnosis often relies on the analysis of large amounts of patient data, and thus lends itself well to support from machine learning algorithms, which are able to learn from past diagnosis and see clearly through the complex interactions of a patient's symptoms and data. Unfortunately, many contemporary machine learning techniques fail to reveal details about how they reach their conclusions, a property considered fundamental when providing a diagnosis. Here we introduce our Personalisable Clinical Decision Support System (PECLIDES), an algorithmic process formulated to address this specific fault in diagnosis detection. PECLIDES provides a clear insight into the decision-making process leading to a diagnosis, making it a gray box model. Our algorithm enriches the fundamental work of Masheyekhi and Gras in data integration, personal medicine, usability, visualization, and interactivity.Our decision support system is an operation of translational medicine. It is based on random forests, is personalisable and allows a clear insight into the decision-making process. A well-structured rule set is created and every rule of the decision-making process can be observed by the user (physician). Furthermore, the user has an impact on the creation of the final rule set and the algorithm allows the comparison of different diseases as well as regional differences in the same disease. The algorithm is applicable to various decision problems. In this paper we will evaluate it on diagnosing neurological diseases and therefore refer to the algorithm as PECLIDES Neuro1.

Accurate and actionable biomarkers that integrate diverse molecular, functional and clinical information hold great promise in precision medicine. Here, the authors develop SIMMS, a method for pathway-based cross-disease biomarker discovery.

Abstract Background Inflammation is a core element of many different, systemic and chronic diseases that usually involve an important autoimmune component. The clinical phase of inflammatory diseases is often the culmination of a long series of pathologic events that started years before. The systemic characteristics and related mechanisms could be investigated through the multi–omic comparative analysis of many inflammatory diseases. Therefore, it is important to use molecular data to study the genesis of the diseases. Here we propose a new methodology to study the relationships between inflammatory diseases and signalling molecules whose dysregulation at molecular levels could lead to systemic pathological events observed in inflammatory diseases. Results We first perform an exploratory analysis of gene expression data of a number of diseases that involve a strong inflammatory component. The comparison of gene expression between disease and healthy samples reveals the importance of members of gene families coding for signalling factors. Next, we focus on interested signalling gene families and a subset of inflammation related diseases with multi–omic features including both gene expression and DNA methylation. We introduce a phylogenetic–based multi–omic method to study the relationships between multi–omic features of inflammation related diseases by integrating gene expression, DNA methylation through sequence based phylogeny of the signalling gene families. The models of adaptations between gene expression and DNA methylation can be inferred from pre–estimated evolutionary relationship of a gene family. Members of the gene family whose expression or methylation levels significantly deviate from the model are considered as the potential disease associated genes. Conclusions Applying the methodology to four gene families (the chemokine receptor family, the TNF receptor family, the TGF– β gene family, the IL–17 gene family) in nine inflammation related diseases, we identify disease associated genes which exhibit significant dysregulation in gene expression or DNA methylation in the inflammation related diseases, which provides clues for functional associations between the diseases.

Tumor-homing peptides (THPs) are small peptides that can recognize and bind cancer cells specifically. To gain a better understanding of THPs’ functional mechanisms, the accurate identification and characterization of THPs is required. Although some computational methods for in silico THP identification have been proposed, a major drawback is their lack of model interpretability. In this study, we propose a new, simple and easily interpretable computational approach (called SCMTHP) for identifying and analyzing tumor-homing activities of peptides via the use of a scoring card method (SCM). To improve the predictability and interpretability of our predictor, we generated propensity scores of 20 amino acids as THPs. Finally, informative physicochemical properties were used for providing insights on characteristics giving rise to the bioactivity of THPs via the use of SCMTHP-derived propensity scores. Benchmarking experiments from independent test indicated that SCMTHP could achieve comparable performance to state-of-the-art method with accuracies of 0.827 and 0.798, respectively, when evaluated on two benchmark datasets consisting of Main and Small datasets. Furthermore, SCMTHP was found to outperform several well-known machine learning-based classifiers (e.g., decision tree, k-nearest neighbor, multi-layer perceptron, naive Bayes and partial least squares regression) as indicated by both 10-fold cross-validation and independent tests. Finally, the SCMTHP web server was established and made freely available online. SCMTHP is expected to be a useful tool for rapid and accurate identification of THPs and for providing better understanding on THP biophysical and biochemical properties.

In this study, Portable Document Format (PDF), Word, Excel, Rich Test format (RTF) and image documents are taken as the research objects to study a static and fast method by which to detect malicious documents. Malicious PDF and Word document features are abstracted and extended, which can be used to detect other types of documents. A universal static detection framework for malicious documents based on feature generalization is then proposed. The generalized features include specification check errors, the structure path, code keywords, and the number of objects. The proposed method is verified on two datasets, and is compared with Kaspersky, NOD32, and McAfee antivirus software. The experimental results demonstrate that the proposed method achieves good performance in terms of the detection accuracy, runtime, and scalability. The average F1-score of all types of documents is found to be 0.99, and the average detection time of a document is 0.5926 s, which is at the same level as the compared antivirus software.

Traditionally marker-based approaches are used to define haematopoietic cell type or state. Here, the authors use single-cell RNA-seq to establish a cellular hierarchy of lineage development in zebrafish haematopoiesis, and propose a refined model of developmental progression of haematopoietic cells.

Abstract Background Human embryonic stem cells (hESCs) potentially offer new routes to study, on the basis of the Developmental Origins of Health and Disease (DOHaD) concept, how the maternal environment during pregnancy influences the offspring’s health and can predispose to chronic disease in later life. Reactive oxygen species (ROS), antioxidant defences and cellular redox status play a key function in gene expression regulation and are involved in diabetes and metabolic syndromes as in ageing. Methods We have, therefore, designed an in vitro cell model of oxidative stress by exposing hESCs to hydrogen peroxide (H2O2) during 72 h, in order to resemble the period of preimplantation embryonic development. Results We have analysed the global gene expression profiles of hESCs (HUES3) exposed to non-cytotoxic H2O2 concentrations, using Illumina microarray HT-12 v4, and we found the differential expression of 569 upregulated and 485 downregulated genes. The most affected gene ontology categories were those related with RNA processing and splicing, oxidation reduction and sterol metabolic processes. We compared our findings with a published RNA-seq profiling dataset of human embryos developed in vitro, thereupon exposed to oxidative stress, and we observed that one of the common downregulated genes between this publication and our data, NEDD1, is involved in centrosome structure and function. Conclusions Therefore, we assessed the presence of supernumerary centrosomes and showed that the percentage of cells with more than two centrosomes increased acutely with H2O2 treatment in hESCs (HUES3 and 7) and in a control somatic cell line (Hs27), inducing a premature entry into senescence.

A significant seasonal variation in tuberculosis (TB) is observed in north India during 2006–2011, particularly in states like Himachal Pradesh, Haryana and Rajasthan. To quantify the seasonal variation, we measure average amplitude (peak to trough distance) across seasons in smear positive cases of TB and observe that it is maximum for Himachal Pradesh (40.01%) and minimum for Maharashtra (3.87%). In north India, smear positive cases peak in second quarter (April–June) and reach a trough in fourth quarter (October–December), however low seasonal variation is observed in southern region of the country. The significant correlations as 0.64 (p-value < 0.001), 0.54 (p-value < 0.01) and 0.42 (p-value < 0.05) are observed between minimum temperature and seasonality of TB at lag-1 in north, central and northeast India respectively. However, in south India, this correlation is not significant.

Background & objectives: Malaria and dengue fever are the most common mosquito-borne diseases in the Southeast Asia region (SEAR). We analysed a temporal record of annual cases of malaria and dengue fever from 1985-2009 in SEAR. Methods: Data of dengue and malaria cases were obtained from WHO website for the period from 1985-2009. El-Nino Southern Oscillation (ENSO) fluctuation data were obtained from NOAA Climate Prediction Centre, Maryland. The wavelet analysis was conducted to analyse the data. Results: Results showed that multiyear cycles of malaria outbreaks appeared in 1986 and 1996, concomitant with the timing of dengue cases at one year lag. The dynamics of both cases pronounce a regime shift in the 1999, when the coupling between dengue and ENSO is also stronger. The statistical significance of this coupling is evident from wavelet band-averaged cross power in 2-4 yr scale (95% confidence level). Interpretation & conclusion: The present analysis suggests that the dengue incidence patterns in SEAR are periodic. There is not much evidence of malaria and ENSO having periodic association in the region; however, dengue fever and ENSO shows statistical significant cross-coherence in the 2-4 yr wavelet band and the results are statistically significant in the last decade. This study also provides statistical evidence of geographical clustering which quantitatively demonstrate the cross-country and cross-epidemic situations that exist across SEAR.

Salmonella enterica are a threat to public health. Current vaccines are not fully effective. The ability to grow in infected tissues within phagocytes is required for S. enterica virulence in systemic disease. As the infection progresses the bacteria are exposed to a complex host immune response. Consequently, in order to continue growing in the tissues, S. enterica requires the coordinated regulation of fitness genes. Bacterial gene regulation has so far been investigated largely using exposure to artificial environmental conditions or to in vitro cultured cells, and little information is available on how S. enterica adapts in vivo to sustain cell division and survival. We have studied the transcriptome, proteome and metabolic flux of Salmonella, and the transcriptome of the host during infection of wild type C57BL/6 and immune-deficient gp91-/-phox mice. Our analyses advance the understanding of how S. enterica and the host behaves during infection to a more sophisticated level than has previously been reported.

Abstract A prime goal in systems biology is the comprehensive use of existing high‐throughput genomic datasets to gain a better understanding of chromatin organization and genome function. In this report, we use chromatin immunoprecipitation (ChIP) data that map protein‐binding sites on the genome, and Hi‐C data that map interactions between DNA fragments in the genome in an integrative approach. We first reanalyzed the contact map of the human genome as determined with Hi‐C and found that long‐range interactions are highly nonrandom; the same DNA fragments are often found interacting together. We then show using ChIP data that these interactions can be explained by the action of the CCCTC‐binding factor (CTCF). These CTCF‐mediated interactions are found both within chromosomes and in between different chromosomes. This makes CTCF a major organizer of both the structure of the chromosomal fiber within each individual chromosome and of the chromosome territories within the cell nucleus.

A directional communication scheme, TRAC, is proposed in this paper to deal with issues in mobile directional communications. Directional communication can bring benefits in terms of spatial reuse, power consumption, and security. Using direction antennas implies that the transmitters must know the direction or location of the receiver. It is necessary to predict the receiver's location to keep the transmitter's antenna pointing in the right direction if nodes travel always. TRAC is composed of the location prediction and antenna adjustment. It predicts a possible circular region where the moving receiver may enter into in the near future. The transmitter points its antenna at the predicted circular region and adjusts the beam-width of its directional antenna to cover the predicted region. The authors validated the TRAC algorithm on some vehicles traces. The validation indicated that the algorithm efficiency of TRAC is larger than 96%. TRAC can be employed in mobile communications without nodes' history movement traces.

Cellular network data traffic can be offload onto opportunistic networks. This paper proposes a Distance-based Opportunistic Publish/Subscribe (DOPS) content dissemination model, which is composed of three layers: application layer, decision-making layer and network layer. When a user wants new content, he/she subscribes on a subscribing server. Users having the contents decide whether to deliver the contents to the subscriber based on the distance information. If in the meantime a content owner has traveled further in the immediate past time than the distance between the owner and the subscriber, the content owner will send the content to the subscriber through opportunistic routing. Simulations provide an evaluation of the data traffic offloading efficiency of DOPS.

The output of state-of-the-art reverse-engineering methods for biological networks is often based on the fitting of a mathematical model to the data. Typically, different datasets do not give single consistent network predictions but rather an ensemble of inconsistent networks inferred under the same reverse-engineering method that are only consistent with the specific experimentally measured data. Here, we focus on an alternative approach for combining the information contained within such an ensemble of inconsistent gene networks called meta-analysis, to make more accurate predictions and to estimate the reliability of these predictions. We review two existing meta-analysis approaches; the Fisher transformation combined coefficient test (FTCCT) and Fisher's inverse combined probability test (FICPT); and compare their performance with five well-known methods, ARACNe, Context Likelihood or Relatedness network (CLR), Maximum Relevance Minimum Redundancy (MRNET), Relevance Network (RN) and Bayesian Network (BN). We conducted in-depth numerical ensemble simulations and demonstrated for biological expression data that the meta-analysis approaches consistently outperformed the best gene regulatory network inference (GRNI) methods in the literature. Furthermore, the meta-analysis approaches have a low computational complexity. We conclude that the meta-analysis approaches are a powerful tool for integrating different datasets to give more accurate and reliable predictions for biological networks.

In a hostile environment, it is important for a transmitter to make its wireless transmission invisible to adversaries because an adversary can detect the transmitter if the received power at its antennas is strong enough. This paper defines a detection probability model to compute the level of a transmitter being detected by a detection system at arbitrary location around the transmitter. Our study proves that the probability of detecting a directional antenna is much lower than that of detecting an omnidirectional antenna if both the directional and omnidirectional antennas provide the same Effective Isotropic Radiated Power (EIRP) in the direction of the receiver. We propose a Minimizing Detection Probability (MinDP) routing algorithm to find a secure routing path in ad hoc networks where nodes employ directional antennas to transmit data to decrease the probability of being detected by adversaries. Our study shows that the MinDP routing algorithm can reduce the total detection probability of deliveries from the source to the destination by over 74%.

Recent analyses of human genome sequences have given rise to impressive advances in identifying non-synonymous single nucleotide polymorphisms (nsSNPs). By contrast, the annotation of nsSNPs and their links to diseases are progressing at a much slower pace. Many of the current approaches to analysing disease-associated nsSNPs use primarily sequence and evolutionary information, while structural information is relatively less exploited. In order to explore the potential of such information, we developed a structure-based approach, Bongo (Bonds ON Graph), to predict structural effects of nsSNPs. Bongo considers protein structures as residue-residue interaction networks and applies graph theoretical measures to identify the residues that are critical for maintaining structural stability by assessing the consequences on the interaction network of single point mutations. Our results show that Bongo is able to identify mutations that cause both local and global structural effects, with a remarkably low false positive rate. Application of the Bongo method to the prediction of 506 disease-associated nsSNPs resulted in a performance (positive predictive value, PPV, 78.5%) similar to that of PolyPhen (PPV, 77.2%) and PANTHER (PPV, 72.2%). As the Bongo method is solely structure-based, our results indicate that the structural changes resulting from nsSNPs are closely associated to their pathological consequences.