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Physics-informed neural networks (PINNs) represent a significant advancement at the intersection of machine learning and physical sciences, offering a powerful framework for solving complex problems governed by physical laws. This survey provides a comprehensive review of the current state of research on PINNs, highlighting their unique methodologies, applications, challenges, and future directions. We begin by introducing the fundamental concepts underlying neural networks and the motivation for integrating physics-based constraints. We then explore various PINN architectures and techniques for incorporating physical laws into neural network training, including approaches to solving partial differential equations (PDEs) and ordinary differential equations (ODEs). Additionally, we discuss the primary challenges faced in developing and applying PINNs, such as computational complexity, data scarcity, and the integration of complex physical laws. Finally, we identify promising future research directions. Overall, this survey seeks to provide a foundational understanding of PINNs within this rapidly evolving field.

Null hypothesis significance testing (NHST) is among the most prominent and widely used methods for analyzing data. At the same time, NHST has been criticized since many years because of misuses and misconceptions that can be found extensively in the scholarly literature. Furthermore, in recent years, NHST has been identified as one reason for the replication crisis because many studies place too much emphasis on statistical significance for drawing conclusions. As a response to those problems, calls for actions have been raised, among others by the American Statistical Association (ASA), to rectify these issues, for instance, by modifying or even abandoning NHST. In this paper, we study the reaction of the community on these discussions. Specifically, we conduct a scientometric analysis of bibliographic records to investigate the publication behavior about the usage of NHST. We conduct a trend analysis for the general community, for specific subject areas and for individual journals. Furthermore, we conduct a change-point analysis to investigate if there are continued movements or actual changes. As a result, we find that for the general community NHST is more popular than ever, however, for particular subject-areas and journals there is a clear heterogeneity and no uniform publication behavior is observable.

Abstract The success of the conversational AI system ChatGPT has triggered an avalanche of studies that explore its applications in research and education. There are also high hopes that, in addition to such particular usages, it could lead to artificial general intelligence (AGI) that means to human-level intelligence. Such aspirations, however, need to be grounded by actual scientific means to ensure faithful statements and evaluations of the current situation. The purpose of this article is to put ChatGPT into perspective and to outline a way forward that might instead lead to an artificial special intelligence (ASI), a notion we introduce. The underlying idea of ASI is based on an environment that consists only of text. We will show that this avoids the problem of embodiment of an agent and leads to a system with restricted capabilities compared to AGI. Furthermore, we discuss gated actions as a means of large language models to moderate ethical concerns.

Scientific machine learning and physics-informed neural networks are novel conceptual approaches that integrate scientific knowledge with methods from data science and deep learning. This emerging field has garnered increasing interest due to its unique features and potential applications. However, key topics and subject-specific applications remain under explored. To address this gap, we conducted a scientometric analysis using large-scale bibliographic and citation data from Scopus. Our study provides a global overview of publication and citation trends, explores the co-occurrence of subject areas to uncover multidisciplinary relationships, and identifies the most collaborative fields. Additionally, we employ a Latent Dirichlet Allocation (LDA) model for topic modeling, introducing a novel information-theoretic approach to determine the optimal number of topics. Furthermore, we conduct a trend analysis based on the convergence behavior of entropy and an interpretation grounded in statistical physics, revealing a consolidation process of research directions indicated as an equilibrium state. Lastly, by analyzing Dirichlet distributions from LDA, we estimate the dimension of the transdisciplinarity of scientific machine learning, offering insights into the primary coherent research areas within this field.

The COVID-19 pandemic presented an unparalleled challenge to global healthcare systems. A central issue revolves around the urgent need to swiftly amass critical biological and medical knowledge concerning the disease, its treatment, and containment. Remarkably, text data remains an underutilized resource in this context. In this paper, we delve into the extraction of COVID-related relations using transformer-based language models, including Bidirectional Encoder Representations from Transformers (BERT) and DistilBERT. Our analysis scrutinizes the performance of five language models, comparing information from both PubMed and Reddit, and assessing their ability to make novel predictions, including the detection of “misinformation.” Key findings reveal that, despite inherent differences, both PubMed and Reddit data contain remarkably similar information, suggesting that Reddit can serve as a valuable resource for rapidly acquiring information during times of crisis. Furthermore, our results demonstrate that language models can unveil previously unseen entities and relations, a crucial aspect in identifying instances of misinformation.

The concept of a digital twin is intriguing as it presents an innovative approach to solving numerous real-world challenges. Initially emerging from the domains of manufacturing and engineering, digital twin research has transcended its origins and now finds applications across a wide range of disciplines. This multidisciplinary expansion has impressively demonstrated the potential of digital twin research. While the simulation aspect of a digital twin is often emphasized, the role of artificial intelligence (AI) and machine learning (ML) is severely understudied. For this reason, in this paper, we highlight the pivotal role of AI and ML for digital twin research. By recognizing that a digital twin is a component of a broader Digital Twin System (DTS), we can fully grasp the diverse applications of AI and ML. In this paper, we explore six AI techniques—(1) optimization (model creation), (2) optimization (model updating), (3) generative modeling, (4) data analytics, (5) predictive analytics and (6) decision making—and their potential to advance applications in health, climate science, and sustainability.

The concept of a digital twin (DT) has gained significant attention in academia and industry because of its perceived potential to address critical global challenges, such as climate change, healthcare, and economic crises. Originally introduced in manufacturing, many attempts have been made to present proper definitions of this concept. Unfortunately, there remains a great deal of confusion surrounding the underlying concept, with many scientists still uncertain about the distinction between a simulation, a mathematical model and a DT. The aim of this paper is to propose a formal definition of a digital twin. To achieve this goal, we utilize a data science framework that facilitates a functional representation of a DT and other components that can be combined together to form a larger entity we refer to as a digital twin system (DTS). In our framework, a DT is an open dynamical system with an updating mechanism, also referred to as complex adaptive system (CAS). Its primary function is to generate data via simulations, ideally, indistinguishable from its physical counterpart. On the other hand, a DTS provides techniques for analyzing data and decision-making based on the generated data. Interestingly, we find that a DTS shares similarities to the principles of general systems theory. This multi-faceted view of a DTS explains its versatility in adapting to a wide range of problems in various application domains such as engineering, manufacturing, urban planning, and personalized medicine.

Text data in the form of natural language is a valuable resource that contains domain-specific information applicable to various applications. An example are electronic health records (eHR) offering comprehensive insights into patients’ health histories, enabling knowledge extraction for clinical diagnosis and treatment. In this paper, we study multi-label text classification (MLTC) of eHR data by introducing two novel MLTC methods based on a threshold-learned convolutional neural network (CNN). We conduct comprehensive comparisons with other multi-label models and binary relevance (BR). Importantly, we do not only optimize the architecture of multi-label classifiers but also of the baseline BR model. As a result, our findings indicate that the adaptive-threshold CNN (AT-CNN) and implicit-threshold CNN (IT-CNN) provide a favorable approximation of a binary CNN (B-CNN) with the added benefit of improved runtime efficiency. The latter is crucial when the number of classes grows larger because the runtime of classifiers based on one-vs-rest mappings becomes increasingly prohibitive for such configurations.

Currently, studies involving a digital twin are gaining widespread interest. While the first fields adopting such a concept were in manufacturing and engineering, lately, interest extends also beyond these fields across all academic disciplines. Given the inviting idea behind a digital twin which allows the efficient exploitation and utilization of simulations such a trend is understandable. The purpose of this paper is to use a scientometrics approach to study the early publication history of the digital twin across academia. Our analysis is based on large-scale bibliographic and citation data from Scopus that provides authoritative information about high-quality publications in essentially all fields of science, engineering and humanities. This paper has four major objectives. First, we obtain a global overview of all publications related to a digital twin across all major subject areas. This analysis provides insights into the structure of the entire publication corpus. Second, we investigate the co-occurrence of subject areas appearing together on publications. This reveals interdisciplinary relations of the publications and identifies the most collaborative fields. Third, we conduct a trend and keyword analysis to gain insights into the evolution of the concept and the importance of keywords. Fourth, based on results from topic modeling using a Latent Dirichlet Allocation (LDA) model we introduce the definition of a scientometric dimension (SD) of digital twin research that allows to summarize an important aspect of the bound diversity of the academic literature.

Abstract High-throughput omics experiments provide a wealth of data for exploring biomedical questions and for advancing translational research. However, despite this great potential, results that enter the clinical practice are scarce even twenty years after the completion of the human genome project. For this reason in this paper, we revisit problems with scientific discovery commonly summarized under the term reproducibility crisis. We will argue that the major problem that hampers progress in translational research is threefold. First, in order to establish biological foundations of disorders or general complex phenotypes, one needs to embrace emergence. Second, there seems to be confusion about the underlying hypotheses tested by omics studies. Third, most contemporary omics studies are designed to perform what can be seen as incremental corroborations of a hypothesis. In order to improve upon these shortcomings, we define a severe testing framework (STF) that can be applied to a large number of omics studies for enhancing scientific discovery in the biomedical sciences. Briefly, STF provides systematic means to trim wild-grown omics studies in a constructive way.

Abstract In recent years there is a data surge of industrial and business data. This posses opportunities and challenges at the same time because the wealth of information is usually buried in complex and frequently disconnected data sets. Predictive maintenance utilizes such data for developing prognostic and diagnostic models that allow the optimization of the life cycle of machine components. In this paper, we address the modeling of the prognostics of machine components from mobile work equipment. Specifically, we are estimating survival curves and hazard rates using parametric and non-parametric models to characterize time dependent failure probabilities of machine components. As a result, we find the presence of different types of censoring masking the presence of different populations that can cause severe problems for statistical estimators and the interpretations of results. Furthermore, we show that the obtained hazard functions for different machine components are complex and versatile and are best modeled via non-parametric estimators. However, notable exceptions for individual machine components can be found amenable for a Generalized-gamma and Weibull model.

Biomedical Named-Entity Recognition (BioNER) has become an essential part of text mining due to the continuously increasing digital archives of biological and medical articles. While there are many well-performing BioNER tools for entities such as genes, proteins, diseases or species, there is very little research into food and dietary constituent named-entity recognition. For this reason, in this paper, we study seven BioNER models for food and dietary constituents recognition. Specifically, we study a dictionary-based model, a conditional random fields (CRF) model and a new hybrid model, called FooDCoNER (Food and Dietary Constituents Named-Entity Recognition), which we introduce combining the former two models. In addition, we study deep language models including BERT, BioBERT, RoBERTa and ELECTRA. As a result, we find that FooDCoNER does not only lead to the overall best results, comparable with the deep language models, but FooDCoNER is also much more efficient with respect to run time and sample size requirements of the training data. The latter has been identified via the study of learning curves. Overall, our results not only provide a new tool for food and dietary constituent NER but also shed light on the difference between classical machine learning models and recent deep language models.

In this article, we introduce a new counting polynomial, namely the orbit polynomial. It is well-known that this polynomial has a unique positive zero δ in the interval [0, 1]. The aim of this paper is to study the specific properties of this polynomial and then determine the location of this root for several classes of complex networks to compare with other graphical measures. Additionally, we compare the unique positive zero measure with several well-known centrality graph measures.

Technological progress has led to powerful computers and communication technologies that penetrate nowadays all areas of science, industry and our private lives. As a consequence, all these areas are generating digital traces of data amounting to big data resources. This opens unprecedented opportunities but also challenges toward the analysis, management, interpretation and responsible usage of such data. In this paper, we discuss these developments and the fields that have been particularly effected by the digital revolution. Our discussion is AI-centered showing domain-specific prospects but also intricacies for the method development in artificial intelligence. For instance, we discuss recent breakthroughs in deep learning algorithms and artificial intelligence as well as advances in text mining and natural language processing, e.g., word-embedding methods that enable the processing of large amounts of text data from diverse sources such as governmental reports, blog entries in social media or clinical health records of patients. Furthermore, we discuss the necessity of further improving general artificial intelligence approaches and for utilizing advanced learning paradigms. This leads to arguments for the establishment of statistical artificial intelligence. Finally, we provide an outlook on important aspects of future challenges that are of crucial importance for the development of all fields, including ethical AI and the influence of bias on AI systems. As potential end-point of this development, we define digital society as the asymptotic limiting state of digital economy that emerges from fully connected information and communication technologies enabling the pervasiveness of AI. Overall, our discussion provides a perspective on the elaborate relatedness of digital data and AI systems.

Abstract The identification of prognostic biomarkers for predicting cancer progression is an important problem for two reasons. First, such biomarkers find practical application in a clinical context for the treatment of patients. Second, interrogation of the biomarkers themselves is assumed to lead to novel insights of disease mechanisms and the underlying molecular processes that cause the pathological behavior. For breast cancer, many signatures based on gene expression values have been reported to be associated with overall survival. Consequently, such signatures have been used for suggesting biological explanations of breast cancer and drug mechanisms. In this paper, we demonstrate for a large number of breast cancer signatures that such an implication is not justified. Our approach eliminates systematically all traces of biological meaning of signature genes and shows that among the remaining genes, surrogate gene sets can be formed with indistinguishable prognostic prediction capabilities and opposite biological meaning. Hence, our results demonstrate that none of the studied signatures has a sensible biological interpretation or meaning with respect to disease etiology. Overall, this shows that prognostic signatures are black-box models with sensible predictions of breast cancer outcome but no value for revealing causal connections. Furthermore, we show that the number of such surrogate gene sets is not small but very large.

Research on the structural complexity of networks has produced many useful results in graph theory and applied disciplines such as engineering and data analysis. This paper is intended as a further contribution to this area of research. Here we focus on measures designed to compare graphs with respect to symmetry. We do this by means of a novel characteristic of a graph G, namely an “orbit polynomial.”A typical term of this univariate polynomial is of the form czn, where c is the number of orbits of size n of the automorphism group of G. Subtracting the orbit polynomial from 1 results in another polynomial that has a unique positive root, which can serve as a relative measure of the symmetry of a graph. The magnitude of this root is indicative of symmetry and can thus be used to compare graphs with respect to that property. In what follows, we will prove several inequalities on the unique positive roots of orbit polynomials corresponding to different graphs, thus showing differences in symmetry. In addition, we present numerical results relating to several classes of graphs for the purpose of comparing the new symmetry measure with existing ones. Finally, it is applied to a set of isomers of the chemical compound adamantane C10H16. We believe that the measure can be quite useful for tackling applications in chemistry, bioinformatics, and structure-oriented drug design.

This article investigates circular formation control problems for a group of anonymous mobile robots in the plane, where all robots can converge asymptotically to a predefined circular orbit around a fixed target point without collision, and maintain any desired relative distances from their neighbors. Given the limited resources for communication and computation of robots, a distributed event-triggered method is firstly designed to reduce dependence on resources in multi-robot systems, where the controller’s action is determined by whether the norm of the event-trigger function exceeds zero through continuous sampling. And then, to further minimize communications costs, a self-triggered strategy is proposed, which only uses discrete states sampled and sent by neighboring robots at their event instants. Furthermore, for the two proposed control laws, a Lyapunov functional is constructed, which allows sufficient stability conditions to be obtained on the circular formation for multi-robot systems. And at the same time, the controllers are proved to exclude Zeno behavior. At last, numerical simulation of controlling uniform and non-uniform circular formations by two control methods are conducted. Simulation results show that the designed controller can control all mobile robots to form either a uniform circular formation or a non-uniform circular formation while maintaining any desired relative distances between robots and guaranteeing that there is no collision during the whole evolution. One of the essential features of the proposed control methods is that they reduce the update rates of controllers and the communication frequency between robots. And also, the spatial order of robots is also preserved throughout the evaluation of the system without collision.

Abstract Background Deciphering the meaning of the human DNA is an outstanding goal which would revolutionize medicine and our way for treating diseases. In recent years, non-coding RNAs have attracted much attention and shown to be functional in part. Yet the importance of these RNAs especially for higher biological functions remains under investigation. Methods In this paper, we analyze RNA-seq data, including non-coding and protein coding RNAs, from lung adenocarcinoma patients, a histologic subtype of non-small-cell lung cancer, with deep learning neural networks and other state-of-the-art classification methods. The purpose of our paper is three-fold. First, we compare the classification performance of different versions of deep belief networks with SVMs, decision trees and random forests. Second, we compare the classification capabilities of protein coding and non-coding RNAs. Third, we study the influence of feature selection on the classification performance. Results As a result, we find that deep belief networks perform at least competitively to other state-of-the-art classifiers. Second, data from non-coding RNAs perform better than coding RNAs across a number of different classification methods. This demonstrates the equivalence of predictive information as captured by non-coding RNAs compared to protein coding RNAs, conventionally used in computational diagnostics tasks. Third, we find that feature selection has in general a negative effect on the classification performance which means that unfiltered data with all features give the best classification results. Conclusions Our study is the first to use ncRNAs beyond miRNAs for the computational classification of cancer and for performing a direct comparison of the classification capabilities of protein coding RNAs and non-coding RNAs.

The idea of a digital twin has recently gained widespread attention. While, so far, it has been used predominantly for problems in engineering and manufacturing, it is believed that a digital twin also holds great promise for applications in medicine and health. However, a problem that severely hampers progress in these fields is the lack of a solid definition of the concept behind a digital twin that would be directly amenable for such big data-driven fields requiring a statistical data analysis. In this paper, we address this problem. We will see that the term ’digital twin’, as used in the literature, is like a Matryoshka doll. For this reason, we unstack the concept via a data-centric machine learning perspective, allowing us to define its main components. As a consequence, we suggest to use the term Digital Twin System instead of digital twin because this highlights its complex interconnected substructure. In addition, we address ethical concerns that result from treatment suggestions for patients based on simulated data and a possible lack of explainability of the underling models.

High-throughput technologies do not only provide novel means for basic biological research but also for clinical applications in hospitals. For instance, the usage of gene expression profiles as prognostic biomarkers for predicting cancer progression has found widespread interest. Aside from predicting the progression of patients, it is generally believed that such prognostic biomarkers also provide valuable information about disease mechanisms and the underlying molecular processes that are causal for a disorder. However, the latter assumption has been challenged. In this paper, we study this problem for prostate cancer. Specifically, we investigate a large number of previously published prognostic signatures of prostate cancer based on gene expression profiles and show that none of these can provide unique information about the underlying disease etiology of prostate cancer. Hence, our analysis reveals that none of the studied signatures has a sensible biological meaning. Overall, this shows that all studied prognostic signatures are merely black-box models allowing sensible predictions of prostate cancer outcome but are not capable of providing causal explanations to enhance the understanding of prostate cancer.

The Cross-Industry Standard Process for Data Mining (CRISP-DM) is a widely accepted framework in production and manufacturing. This data-driven knowledge discovery framework provides an orderly partition of the often complex data mining processes to ensure a practical implementation of data analytics and machine learning models. However, the practical application of robust industry-specific data-driven knowledge discovery models faces multiple data- and model development-related issues. These issues need to be carefully addressed by allowing a flexible, customized and industry-specific knowledge discovery framework. For this reason, extensions of CRISP-DM are needed. In this paper, we provide a detailed review of CRISP-DM and summarize extensions of this model into a novel framework we call Generalized Cross-Industry Standard Process for Data Science (GCRISP-DS). This framework is designed to allow dynamic interactions between different phases to adequately address data- and model-related issues for achieving robustness. Furthermore, it emphasizes also the need for a detailed business understanding and the interdependencies with the developed models and data quality for fulfilling higher business objectives. Overall, such a customizable GCRISP-DS framework provides an enhancement for model improvements and reusability by minimizing robustness-issues.

Genomics data provide great opportunities for translational research and the clinical practice, for example, for predicting disease stages. However, the classification of such data is a challenging task due to their high dimensionality, noise, and heterogeneity. In recent years, deep learning classifiers generated much interest, but due to their complexity, so far, little is known about the utility of this method for genomics. In this paper, we address this problem by studying a computational diagnostics task by classification of breast cancer and inflammatory bowel disease patients based on high‐dimensional gene expression data. We provide a comprehensive analysis of the classification performance of deep belief networks (DBNs) in dependence on its multiple model parameters and in comparison with support vector machines (SVMs). Furthermore, we investigate combined classifiers that integrate DBNs with SVMs. Such a classifier utilizes a DBN as representation learner forming the input for a SVM. Overall, our results provide guidelines for the complex usage of DBN for classifying gene expression data from complex diseases.

The ultimate goal of the social sciences is to find a general social theory encompassing all aspects of social and collective phenomena. The traditional approach to this is very stringent by trying to find causal explanations and models. However, this approach has been recently criticized for preventing progress due to neglecting prediction abilities of models that support more problem-oriented approaches. The latter models would be enabled by the surge of big Web-data currently available. Interestingly, this problem cannot be overcome with methods from computational social science (CSS) alone because this field is dominated by simulation-based approaches and descriptive models. In this article, we address this issue and argue that the combination of big social data with social networks is needed for creating prediction models. We will argue that this alliance has the potential for gradually establishing a causal social theory. In order to emphasize the importance of integrating big social data with social networks, we call this approach data-driven computational social network science (DD-CSNS).

At the beginning of 2020, the COVID-19 pandemic was able to spread quickly in Wuhan and in the province of Hubei due to a lack of experience with this novel virus. Additionally, authories had no proven experience with applying insufficient medical, communication and crisis management tools. For a considerable period of time, the actual number of people infected was unknown. There were great uncertainties regarding the dynamics and spread of the Covid-19 virus infection. In this paper, we develop a system dynamics model for the three connected regions (Wuhan, Hubei excl. Wuhan, China excl. Hubei) to understand the infection and spread dynamics of the virus and provide a more accurate estimate of the number of infected people in Wuhan and discuss the necessity and effectivity of protective measures against this epidemic, such as the quarantines imposed throughout China. We use the statistics of confirmed cases of China excl. Hubei. Also the daily data on travel activity within China was utilized, in order to determine the actual numerical development of the infected people in Wuhan City and Hubei Province. We used a multivariate Monte Carlo optimization to parameterize the model to match the official statistics. In particular, we used the model to calculate the infections, which had already broken out, but were not diagnosed for various reasons.

The field artificial intelligence (AI) was founded over 65 years ago. Starting with great hopes and ambitious goals the field progressed through various stages of popularity and has recently undergone a revival through the introduction of deep neural networks. Some problems of AI are that, so far, neither the “intelligence” nor the goals of AI are formally defined causing confusion when comparing AI to other fields. In this paper, we present a perspective on the desired and current status of AI in relation to machine learning and statistics and clarify common misconceptions and myths. Our discussion is intended to lift the veil of vagueness surrounding AI to reveal its true countenance.

The number of scientific publications in the literature is steadily growing, containing our knowledge in the biomedical, health, and clinical sciences. Since there is currently no automatic archiving of the obtained results, much of this information remains buried in textual details not readily available for further usage or analysis. For this reason, natural language processing (NLP) and text mining methods are used for information extraction from such publications. In this paper, we review practices for Named Entity Recognition (NER) and Relation Detection (RD), allowing, e.g., to identify interactions between proteins and drugs or genes and diseases. This information can be integrated into networks to summarize large-scale details on a particular biomedical or clinical problem, which is then amenable for easy data management and further analysis. Furthermore, we survey novel deep learning methods that have recently been introduced for such tasks.

Deep learning models stand for a new learning paradigm in artificial intelligence (AI) and machine learning. Recent breakthrough results in image analysis and speech recognition have generated a massive interest in this field because also applications in many other domains providing big data seem possible. On a downside, the mathematical and computational methodology underlying deep learning models is very challenging, especially for interdisciplinary scientists. For this reason, we present in this paper an introductory review of deep learning approaches including Deep Feedforward Neural Networks (D-FFNN), Convolutional Neural Networks (CNNs), Deep Belief Networks (DBNs), Autoencoders (AEs), and Long Short-Term Memory (LSTM) networks. These models form the major core architectures of deep learning models currently used and should belong in any data scientist's toolbox. Importantly, those core architectural building blocks can be composed flexibly—in an almost Lego-like manner—to build new application-specific network architectures. Hence, a basic understanding of these network architectures is important to be prepared for future developments in AI.

Modern molecular high-throughput devices, e.g., next-generation sequencing, have transformed medical research. Resulting data sets are usually high-dimensional on a genomic-scale providing multi-factorial information from intertwined molecular and cellular activities of genes and their products. This genomics-revolution installed precision medicine offering breathtaking opportunities for patient's diagnosis and treatment. However, due to the speed of these developments the quality standards of the involved data analyses are lacking behind, as exemplified by the infamous Duke Saga. In this paper, we argue in favor of a two-stage cooperative serve model that couples data generation and data analysis in the most beneficial way from the perspective of a patient to ensure data analysis quality standards including reproducible research.

Abstract Background sgnesR (Stochastic Gene Network Expression Simulator in R) is an R package that provides an interface to simulate gene expression data from a given gene network using the stochastic simulation algorithm (SSA). The package allows various options for delay parameters and can easily included in reactions for promoter delay, RNA delay and Protein delay. A user can tune these parameters to model various types of reactions within a cell. As examples, we present two network models to generate expression profiles. We also demonstrated the inference of networks and the evaluation of association measure of edge and non-edge components from the generated expression profiles. Results The purpose of sgnesR is to enable an easy to use and a quick implementation for generating realistic gene expression data from biologically relevant networks that can be user selected. Conclusions sgnesR is freely available for academic use. The R package has been tested for R 3.2.0 under Linux, Windows and Mac OS X.

Social media data, for instance from Twitter or Facebook, provide a new type of data that consist of a mixture of text, image and video information. From a scientific point of view, the capabilities of this type of data from such microblogs are not well explored and to date it is largely unknown what principal knowledge can be extracted thereof. In this paper, we present a discussion of the capabilities of data from microblogs for performing a psychoanalysis. This could allow an analysis of the human personality of individual users. Such prospects raises serious concerns regarding the privacy of users of social media platforms.

The LINCS L1000 data repository contains almost two million gene expression profiles for thousands of small molecules and drugs. However, due to the complexity and the size of the data repository and a lack of an interoperable interface, the creation of pharmacologically meaningful workflows utilizing these data is severely hampered. In order to overcome this limitation, we developed the L1000 Viewer, a search engine and graphical web interface for the LINCS data repository. The web interface serves as an interactive platform allowing the user to select different forms of perturbation profiles, e.g., for specific cell lines, drugs, dosages, time points and combinations thereof. At its core, our method has a database we created from inferring and utilizing the intricate dependency graph structure among the data files. The L1000 Viewer is accessible via http://L1000viewer.bio-complexity.com/.

Glioblastoma (GBM) is the most common type of malignant brain tumor in adults. We show here that small molecule 2-[(3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl]phenol (THTMP), a potential anticancer agent, increases the human glioblastoma cell death. Its mechanism of action and the interaction of selective signaling pathways remain elusive. Three structurally related phenolic compounds were tested in multiple glioma cell lines in which the potential activity of the compound, THTMP, was further validated and characterized. Upon prolonged exposer to THTMP, all glioma cell lines undergo p53 and cyclin-dependent kinase mediated cell death with the IC50 concentration of 26.5 and 75.4 μM in LN229 and Snb19, respectively. We found that THTMP strongly inhibited cell growth in a dose and in time dependent manner. THTMP treatment led to G1/S cell cycle arrest and apoptosis induction of glioma cell lines. Furthermore, we identified 3,714 genes with significant changes at the transcriptional level in response to THTMP. Further, a transcriptional analysis (RNA-seq) revealed that THTMP targeted the p53 signaling pathway specific genes causing DNA damage and cell cycle arrest at G1/S phase explained by the decrease of cyclin-dependent kinase 1, cyclin A2, cyclin E1 and E2 in glioma cells. Consistently, THTMP induced the apoptosis by regulating the expression of Bcl-2 family genes and reactive oxygen species while it also changed the expression of several anti-apoptotic genes. These observations suggest that THTMP exerts proliferation activity inhibition and pro-apoptosis effects in glioma through affecting cell cycle arrest and intrinsic apoptosis signaling. Importantly, THTMP has more potential at inhibiting GBM cell proliferation compared to TMZ, the current chemotherapy treatment administered to GBM patients; thus, we propose that THTMP may be an alternative therapeutic option for glioblastoma.

High-dimensional data from molecular biology possess an intricate correlation structure that is imposed by the molecular interactions between genes and their products forming various different types of gene networks. This fact is particularly well-known for gene expression data, because there is a sufficient number of large-scale data sets available that are amenable for a sensible statistical analysis confirming this assertion. The purpose of this paper is two fold. First, we investigate three methods for generating constrained covariance matrices with a biologically realistic structure. Such covariance matrices are playing a pivotal role in designing novel statistical methods for high-dimensional biological data, because they allow to define Gaussian graphical models (GGM) for the simulation of realistic data; including their correlation structure. We study local and global characteristics of these covariance matrices, and derived concentration/partial correlation matrices. Second, we connect these results, obtained from a probabilistic perspective, to statistical results of studies aiming to estimate gene regulatory networks from biological data. This connection allows to shed light on the well-known heterogeneity of statistical estimation methods for inferring gene regulatory networks and provides an explanation for the difficulties inferring molecular interactions between highly connected genes.

Prostate cancer is the most common cancer type in men in Finland and second worldwide. In this paper, we analyze almost 150, 000 published papers about prostate cancer, authored by ten thousands of scientists worldwide, with an integrated text mining and computational network theory approach. We demonstrate how to integrate text mining with network analysis investigating research contributions of countries and collaborations within and between countries. Furthermore, we study the time evolution of individually and collectively studied genes. Finally, we investigate a collaboration network of Finland and compare studied genes with globally studied genes in prostate cancer genetics. Overall, our results provide a global overview of prostate cancer research in genetics. In addition, we present a specific discussion for Finland. Our results shed light on trends within the last 30 years and are useful for translational researchers within the full range from genetics to public health management and health policy.

Gene set analysis (GSA) has become the common methodology for analyzing transcriptomics data. However, self-contained GSA techniques are rarely, if ever, used for proteomics data analysis. Here we present a self-contained proteome level GSA of four consensus molecular subtypes (CMSs) previously established by transcriptome dissection of colon carcinoma specimens. Despite notable difference in structure of proteomics and transcriptomics data, many pathway-wide characteristic features of CMSs found at the mRNA level were reproduced at the protein level. In particular, CMS1 features show heavy involvement of immune system as well as the pathways related to mismatch repair, DNA replication and functioning of proteasome, while CMS4 tumors upregulate complement pathway and proteins participating in epithelial-to-mesenchymal transition (EMT). In addition, protein level GSA yielded a set of novel observations visible at the proteome, but not at the transcriptome level, including possible involvement of major histocompatibility complex II (MHC-II) antigens in the known immunogenicity of CMS1 and a connection between cholesterol trafficking and the regulation of Integrin-linked kinase (ILK) in CMS3. Overall, this study proves utility of self-contained GSA approaches as a critical tool for analyzing proteomics data in general and dissecting protein-level molecular portraits of human tumors in particular.

In this paper, we define novel graph measures for directed networks. The measures are based on graph polynomials utilizing the out- and in-degrees of directed graphs. Based on these polynomial, we define another polynomial and use their positive zeros as graph measures. The measures have meaningful properties that we investigate based on analytical and numerical results. As the computational complexity to compute the measures is polynomial, our approach is efficient and can be applied to large networks. We emphasize that our approach clearly complements the literature in this field as, to the best of our knowledge, existing complexity measures for directed graphs have never been applied on a large scale.

The size of the orbits or similar vertices of a network provides important information regarding each individual component of the network. In this paper, we investigate the entropy or information content and the symmetry index for several classes of graphs and compare the values of this measure with that of the symmetry index of certain graphs.

This paper considers commuting graphs over the semidihedral group SD8n. We compute their eigenvalues and obtain that these commuting graphs are not hyperenergetic for odd n≥15 or even n≥2. We further compute the Laplacian spectrum, the Laplacian energy and the number of spanning trees of the commuting graphs over SD8n. We also discuss vertex connectivity, planarity, and minimum disconnecting sets of these graphs and prove that these commuting graphs are not Hamiltonian.

If G is a graph and P is a partition of V(G), then the partition distance of G is the sum of the distances between all pairs of vertices that lie in the same part of P. A colored distance is the dual concept of the partition distance. These notions are motivated by a problem in the facility location network and applied to several well-known distance-based graph invariants. In this paper, we apply an extended cut method to induce the partition and color distances to some subsets of vertices which are not necessary a partition of V(G). Then, we define a two-dimensional weighted graph and an operator to prove that the induced partition and colored distances of a graph can be obtained from the weighted Wiener index of a two-dimensional weighted quotient graph induced by the transitive closure of the Djoković–Winkler relation as well as by any partition that is coarser. Finally, we utilize our main results to find some upper bounds for the modified Wiener index and the number of orbits of partial cube graphs under the action of automorphism group of graphs.

The orbit polynomial is a new graph counting polynomial which is defined as OG(x)=∑i=1rx|Oi|, where O1, …, Or are all vertex orbits of the graph G. In this article, we investigate the structural properties of the automorphism group of a graph by using several novel counting polynomials. Besides, we explore the orbit polynomial of a graph operation. Indeed, we compare the degeneracy of the orbit polynomial with a new graph polynomial based on both eigenvalues of a graph and the size of orbits.

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Symmetry is an important visual feature for humans and its application in architecture is completely evident. This paper aims to investigate the role of symmetry in the aesthetics judgment of residential building façades and study the pattern of eye movement based on the expertise of subjects in architecture. In order to implement this in the present paper, we have created images in two categories: symmetrical and asymmetrical façade images. The experiment design allows us to investigate the preference of subjects and their reaction time to decide about presented images as well as record their eye movements. It was inferred that the aesthetic experience of a building façade is influenced by the expertise of the subjects. There is a significant difference between experts and non-experts in all conditions, and symmetrical façades are in line with the taste of non-expert subjects. Moreover, the patterns of fixational eye movements indicate that the horizontal or vertical symmetry (mirror symmetry) has a profound influence on the observer’s attention, but there is a difference in the points watched and their fixation duration. Thus, although symmetry may attract the same attention during eye movements on façade images, it does not necessarily lead to the same preference between the expert and non-expert groups.

A fullerene is a cubic three-connected graph whose faces are entirely composed of pentagons and hexagons. Entropy applied to graphs is one of the significant approaches to measuring the complexity of relational structures. Recently, the research on complex networks has received great attention, because many complex systems can be modelled as networks consisting of components as well as relations among these components. Information—theoretic measures have been used to analyze chemical structures possessing bond types and hetero-atoms. In the present article, we reviewed various entropy-based measures on fullerene graphs. In particular, we surveyed results on the topological information content of a graph, namely the orbit-entropy Ia(G), the symmetry index, a degree-based entropy measure Iλ(G), the eccentric-entropy Ifσ(G) and the Hosoya entropy H(G).

Cancer stem cells (CSCs), a small subpopulation of cells existing in the tumor microenvironment promoting cell proliferation and growth. Targeting the stemness of the CSC population would offer a vital therapeutic opportunity. 3,4-Dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol (THTMP), a small synthetic phenol compound, is proposed to play a significant role in controlling the CSC proliferation and survival. We assessed the potential therapeutic effects of THTMP on glioblastoma multiforme (GBM) and its underlying mechanism in various signaling pathways. To fully comprehend the effect of THTMP on the CSCs, CD133+ GBM stem cell (GSC) and CD133- GBM Non-stem cancer cells (NSCC) population from LN229 and SNB19 cell lines was used. Cell cycle arrest, apoptosis assay and transcriptome analysis were performed for individual cell population. THTMP strongly inhibited NSCC and in a subtle way for GSC in a time-dependent manner and inhibit the resistance variants better than that of temozolomide (TMZ). THTMP arrest the CSC cell population at both G1/S and G2/M phase and induce ROS-mediated apoptosis. Gene expression profiling characterize THTMP as an inhibitor of the p53 signaling pathway causing DNA damage and cell cycle arrest in CSC population. We show that the THTMP majorly affects the EGFR and CSC signaling pathways. Specifically, modulation of key genes involved in Wnt, Notch and Hedgehog, revealed the significant role of THTMP in disrupting the CSCs’ stemness and functions. Moreover, THTMP inhibited cell growth, proliferation and metastasis of multiple mesenchymal patient-tissue derived GBM-cell lines. THTMP arrests GBM stem cell cycle through the modulation of EGFR and CSC signaling pathways.