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The ratio of protein to creatinine (PCR) in urine is a measure of kidney health of a human body. We report the development of a point-of-care (POC) kidney function test (KFT) kit, which is composed of a paper-based PCR sensor, an opto-electrochemical measurement unit, a display, and a facility to transfer data to a smartphone. For the total protein sensor, the pieces of filter papers were coated with a mixture of alcoholic bromophenol blue and citric buffer leading to a chrome-yellow coloration. While for the creatinine sensor the papers were coated with alkaline picrate solution leading to a lemon-yellow coloration of the surface. Dispensing protein (creatinine) solution of known concentration on the respective sensors led to the conversion of chrome-yellow to bluish-green coloration (lemon-yellow to orange coloration) for the total protein (creatinine) sensor. The intensity of such colorations varied with the concentration of the analytes in the solutions. The variations in the intensities of colors with analyte concentration were quantified by integrating a light emitting diode (LED) at one side of each sensor and a light intensity sensor (LIS) on the other side. The intensity of the transmitted rays, passing through the sensors, was found to vary the electrical output of the LIS monotonically with the loading of the total protein or creatinine in the analyte. This helped in obtaining the calibration plots for the PCR sensors. Further, the sensors were employed for the on-spot detection of the unknown PCR in the real human urine samples. [ABSTRACT FROM AUTHOR]

Network alignment is a critical task in a wide variety of fields. Many existing works leverage on representation learning to accomplish this task without eliminating domain representation bias induced by domain-dependent features, which yield inferior alignment performance. This paper proposes a unified deep architecture (DANA) to obtain a domain-invariant representation for network alignment via an adversarial domain classifier. Specifically, we employ the graph convolutional networks to perform network embedding under the domain adversarial principle, given a small set of observed anchors. Then, the semi-supervised learning framework is optimized by maximizing a posterior probability distribution of observed anchors and the loss of a domain classifier simultaneously. We also develop a few variants of our model, such as, direction-aware network alignment, weight-sharing for directed networks and simplification of parameter space. Experiments on three real-world social network datasets demonstrate that our proposed approaches achieve state-of-the-art alignment results. [ABSTRACT FROM AUTHOR]

Network embedding has been widely employed in networked data mining applications as it can learn low-dimensional and dense node representations from the high-dimensional and sparse network structure. While most existing network embedding methods only model the proximity between two nodes regardless of the order of the proximity, this paper proposes to explicitly model multi-node proximities which can be widely observed in practice, e.g., multiple researchers coauthor a paper, and multiple genes co-express a protein. Explicitly modeling multi-node proximities is important because some two-node interactions may not come into existence without a third node. By proving that LINE(1st), a recent network embedding method, is equivalent to kernelized matrix factorization, this paper proposes coupled kernelized multi-dimensional array factorization (Cetera) which jointly factorizes multiple multi-dimensional arrays by enforcing a consensus representation for each node. In this way, node representations can be more comprehensive and effective, which is demonstrated on three real-world networks through link prediction and multi-label classification. [ABSTRACT FROM AUTHOR]

Ulcers and chronic wounds are a large and expensive problem, costing billions of pounds a year and affecting millions of people. Electrical stimulation has been known to have a positive effect on wound healing since the 1960s and this has been confirmed in numerous studies, reducing the time to heal, and the incidence of adverse events such as infections. However, because each study used different parameters for the treatment, inclusion criteria and metrics for quantifying the success, it is currently hard to combine them statistically and gain a true picture of its efficacy. As such, electrical stimulation has not been universally adopted as a recommended treatment for various types of wound. This paper summarises the biological basis for electrical simulation treatment and reviews the clinical evidence for its effectiveness. Notable is the lack of research focused on the electrodes used to deliver electrostimulation treatment. However, a significant amount of work has been conducted on electrodes for other medical applications in the field of e-textiles. This e-textile work is reviewed with a focus on its potential in electrostimulation and proposals are made for future developments to improve future studies and applications for wound healing via electrical stimulation. [ABSTRACT FROM AUTHOR]

Molecular communication is an emerging communication paradigm for biological nanomachines. It allows biological nanomachines to communicate through exchanging molecules in an aqueous environment and to perform collaborative tasks through integrating functionalities of individual biological nanomachines. This paper develops the layered architecture of molecular communication and describes research issues that molecular communication faces at each layer of the architecture. Specifically, this paper applies a layered architecture approach, traditionally used in communication networks, to molecular communication, decomposes complex molecular communication functionality into a set of manageable layers, identifies basic functionalities of each layer, and develops a descriptive model consisting of key components of the layer for each layer. This paper also discusses open research issues that need to be addressed at each layer. In addition, this paper provides an example design of targeted drug delivery, a nanomedical application, to illustrate how the layered architecture helps design an application of molecular communication. The primary contribution of this paper is to provide an in-depth architectural view of molecular communication. Establishing a layered architecture of molecular communication helps organize various research issues and design concerns into layers that are relatively independent of each other, and thus accelerates research in each layer and facilitates the design and development of applications of molecular communication. [ABSTRACT FROM PUBLISHER]

How do alliances lead to knowledge growth and learning for parent firms? Prior research focuses on knowledge inflows from a partner when a firm enters into an alliance. In this paper, we examine factors that enable firms to make better use of their own knowledge and capabilities as a consequence of alliances. To demonstrate the latter dimension of knowledge growth, we depart from prior research that has focused on cross citations of patents between partners, and instead a study self-citation activity. We examine the effect of four factors on self-citations, each of which reflects distinct learning mechanisms and cooperative dynamics, namely knowledge inflows from the alliance partner, knowledge outflows to the alliance partner, partner characteristics, and alliance governance. Results suggest that knowledge inflows from the partner were positively associated with changes in self-citations in alliance domains, whereas knowledge outflows to the partner had a positive impact on changes in self-citations for the smaller firm in the alliance. In contrast, firm specific knowledge possessed by the partner and equity governance had a negative impact on changes in self-citations in alliance domains. This paper develops a fuller understanding of the learning effects of alliances by highlighting that apart from better utilization of the partner's capabilities, alliances also lead to enhanced utilization of the firm's own knowledge and capabilities in further innovative activity. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) epidemic continues to spread rapidly around the world and nearly 20 millions people are infected. This paper utilises both single-locus analysis and joint-SNPs analysis for detection of significant single nucleotide polymorphisms (SNPs) in the phenotypes of symptomatic versus asymptomatic, the early collection time versus the late collection time, the old versus the young, and the male versus the female. Also, this paper analyses the relationship between any two SNPs via linkage disequilibrium analysis, and visualises the patterns of cumulative mutations of SNPs over collection time. The results are in three folds. First, the SNP which locates at the nucleotide position 4321 is found to be an independent significant locus associated with all the first three phenotypes. Moreover, 12 significant SNPs are found in the first two studies. Second, gene orf1ab containing SNP-4321 is detected to be significantly associated with the first three phenotypes, and the three genes S, ORF3a, and N, are detected to be significant in the first two phenotypes. Third, some of the detected genes or SNPs are related to the SARS-COV-2 as supported by literature survey, which indicates that the results here may be helpful for further investigation. [ABSTRACT FROM AUTHOR]

In general, flexible ligand docking is used for docking simulations under the premise that the position of the binding site is already known, and meanwhile it can also be used without prior knowledge of the binding site. However, most of the optimization search algorithms used in popular docking software are far from being ideal in the first case, and they can hardly be directly utilized for the latter case due to the relatively large search area. In order to design an algorithm that can flexibly adapt to different sizes of the search area, we propose an effective swarm intelligence optimization algorithm in this paper, called diversity-controlled Lamarckian quantum particle swarm optimization (DCL-QPSO). The highlights of the algorithm are a diversity-controlled strategy and a modified local search method. Integrated with the docking environment of Autodock, the DCL-QPSO is compared with Autodock Vina, Glide and other two Autodock-based search algorithms for flexible ligand docking. Experimental results revealed that the proposed algorithm has a performance comparable to those of Autodock Vina and Glide for dockings within a certain area around the binding sites, and is a more effective solver than all the compared methods for dockings without prior knowledge of the binding sites. [ABSTRACT FROM AUTHOR]

This paper explores the use of variants of tf-idf-based descriptors, namely length-normalized-tf-idf and log-normalized-tf-idf, combined with a segmentation technique, for efficient modeling of variable-length protein sequences. The proposed solution, ProtVecGen-Ensemble, is an ensemble of three models trained on differently segmented datasets constructed from an input dataset containing complete protein sequences. Evaluations using biological process (BP) and molecular function (MF) datasets demonstrate that the proposed feature set is not only superior to its contemporaries but also produces more consistent results with respect to variation in sequence lengths. Improvements of +6.07% (BP) and +7.56% (MF) over state-of-the-art tf-idf-based MLDA feature set were obtained. The best results were achieved when ProtVecGen-Ensemble was combined with ProtVecGen-Plus — the state-of-the-art method for protein function prediction — resulting in improvements of +8.90% (BP) and +11.28% (MF) over MLDA and +1.49% (BP) and +2.07% (MF) over ProtVecGen-Plus+MLDA. To capture the performance consistency with respect to sequence lengths, we have defined a variance-based metric, with lower values indicating better performance. On this metric, the proposed ProtVecGen-Ensemble+ProtVecGen-Plus framework resulted in reductions of 56.85 percent (BP) and 56.08 percent (MF) over MLDA and 10.37 percent (BP) and 26.48 percent (MF) over ProtVecGenPlus+MLDA. [ABSTRACT FROM AUTHOR]

Eukaryotic initiation factor 2 (eIF2) is a central controller of the eukaryotic translational machinery. To sustain the on-going translation activity, eIF2 cycles between its GTP and GDP bound states. However, in response to cellular stresses, the phosphorylation of eIF2 takes place, which acts as an inhibitor of the guanine nucleotide exchange factor eIF2B and switches the translation activity on physiological timescales. The main objective of this paper is to investigate the stability of the regulatory system under nominal conditions, parametric fluctuations, and structural damages. In this paper, a mathematical model of eIF2-dependent regulatory system is used to identify the stability-conferring features within the system with the help of direct and indirect methods of Lyapunov stability theory. To investigate the impact of intrinsic fluctuations and structural damages on the stability of regulatory system, the mathematical model has been linearized around feasible equilibrium point and the variation of system poles has been observed. The investigations have revealed that the regulatory model is stable and able to tolerate the intrinsic stressors but becomes unstable when particular complex is targeted to override the undesirable interaction. Our analyses indicate that, the stability is a collective property and damage in the structure of the system changes the stability of the system. [ABSTRACT FROM AUTHOR]

This paper deals with an abstraction of a unified problem of drug discovery and pathogen identification. Pathogen identification involves the identification of disease-causing biomolecules. Drug discovery involves finding chemical compounds, called lead compounds, that bind to pathogenic proteins and eventually inhibit the function of the protein. In this paper, the lead compounds are abstracted as inhibitors, pathogenic proteins as defectives, and the mixture of “ineffective” chemical compounds and non-pathogenic proteins as normal items. A defective could be immune to the presence of an inhibitor in a test. So, a test containing a defective is positive if it does not contain its “associated” inhibitor. The goal of this paper is to identify the defectives, inhibitors, and their “associations” with high probability, or in other words, learn the immune defectives graph (IDG) efficiently through group tests. We propose a probabilistic non-adaptive pooling design, a probabilistic two-stage adaptive pooling design, and decoding algorithms for learning the IDG. For the two-stage adaptive-pooling design, we show that the sample complexity of the number of tests required to guarantee recovery of the inhibitors, defectives, and their associations with high probability, i.e., the upper bound, exceeds the proposed lower bound by a logarithmic multiplicative factor in the number of items. To be precise, lower and upper bounds of $\Omega ((r+d)\log n + rd)$ and O(rd \log n)$ tests, respectively, are identified for classifying r$ inhibitors and d$ defectives amongst n tests) exceeds the proposed lower bound (given by \max \{\Omega ((r+d)\log n + rd),\Omega (({r^{2}}/{\log r})\log n),\Omega (d^{2})\} tests) by at most a logarithmic multiplicative factor in the number of items. [ABSTRACT FROM AUTHOR]

For the past decades, computational methods have been developed to predict various interactions in biological problems. Usually these methods treated the predicting problems as semi-supervised problem or positive-unlabeled(PU) learning problem. Researchers focused on the prediction of unlabeled samples and hoped to find novel interactions in the datasets they collected. However, most of the computational methods could only predict a small proportion of undiscovered interactions and the total number was unknown. In this paper, we developed an estimation method with deep learning to calculate the number of undiscovered interactions in the unlabeled samples, derived its asymptotic interval estimation, and applied it to the compound synergism dataset, drug-target interaction(DTI) dataset and MicroRNA-disease interaction dataset successfully. Moreover, this method could reveal which dataset contained more undiscovered interactions and would be a guidance for the experimental validation. Furthermore, we compared our method with some mixture proportion estimators and demonstarted the efficacy of our method. Finally, we proved that AUC and AUPR were related with the number of undiscovered interactions, which was regarded as another evaluation indicator for the computational methods. [ABSTRACT FROM AUTHOR]

Over the past decade, the demand for automated protein function prediction has increased due to the volume of newly sequenced proteins. In this paper, we address the function prediction task by developing an ensemble system automatically assigning Gene Ontology (GO) terms to the given input protein sequence. We develop an ensemble system which combines the GO predictions made by random forest (RF) and neural network (NN) classifiers. Both RF and NN models rely on features derived from BLAST sequence alignments, taxonomy and protein signature analysis tools. In addition, we report on experiments with a NN model that directly analyzes the amino acid sequence as its sole input, using a convolutional layer. The Swiss-Prot database is used as the training and evaluation data. In the CAFA3 evaluation, which relies on experimental verification of the functional predictions, our submitted ensemble model demonstrates competitive performance ranking among top-10 best-performing systems out of over 100 submitted systems. In this paper, we evaluate and further improve the CAFA3-submitted system. Our machine learning models together with the data pre-processing and feature generation tools are publicly available as an open source software at https://github.com/TurkuNLP/CAFA3. [ABSTRACT FROM AUTHOR]

This article is concerned with the problem of finite-time $\mathcal {H}_{\infty }$ H ∞ state estimation for switched genetic regulatory networks with randomly occurring uncertainties. The persistent dwell-time switching rule, as a more versatile class of switching rules, is considered in this paper. Besides, several random variables that obey the Bernoulli distribution are used to represent randomly occurring uncertainties. The overriding purpose of this article is to design an estimator to ensure that the estimation error system is stochastically finite-time bounded and satisfies the $\mathcal {H}_{\infty }$ H ∞ performance. Based on this, sufficient conditions for the explicit form of the estimator gains can be obtained by the Lyapunov method. Finally, a numerical example is given to verify the correctness and feasibility of the proposed method. [ABSTRACT FROM AUTHOR]

Identifying functional modules in protein-protein interaction (PPI) networks elucidates cellular organization and mechanism. Various methods have been proposed to identify the functional modules in PPI networks, but most of these methods do not consider the noisy links in PPI networks. They achieve a competitive performance on the PPI networks without noisy links, but the performance of these methods considerably deteriorates in the noisy PPI networks. Furthermore, the noisy links are inevitable in the PPI networks. In this paper, we propose a novel link-driven label propagation algorithm (LLPA) to identify functional modules in PPI networks. The LLPA first find link clusters in PPI networks, and then the functional modules are identified from the link clusters. Two strategies aimed to ensure the robustness of LLPA are proposed. One strategy involves the proposed LLPA updating the link labels in accordance with the designed weight of the link, which can reduce the incidence of noisy links. The other strategy involves the filtration of some noisy labels from the link clusters to further reduce the influence of noisy links. The performance evaluation on three real PPI networks shows that LLPA outperforms other eight state-of-the-art detection algorithms in terms of accuracy and robustness. [ABSTRACT FROM AUTHOR]

The identification of drug side-effects is considered to be an important step in drug design, which could not only shorten the time but also reduce the cost of drug development. In this paper, we investigate the relationship between the potential side-effects of drug candidates and their chemical structures. The preliminary Regularized Regression (RR) model for drug side-effects prediction has promising features in the efficiency of model training and the existence of a closed form solution. It performs better than other state-of-the-art methods, in terms of minimum accuracy and average accuracy. In order to dig inside how drug structure will associate with side effect, we further propose weighted GTS (Generalized T-Student Kernel: WGTS) SVM model from a structural risk minimization perspective. The SVM model proposed in this paper provides a better understanding of drug side-effects in the process of drug development. The usefulness of the WGTS model lies in the superior performance in a cross validation setting on 888 approved drugs with 1385 side-effects profiling from SIDER database. This work is expected to shed light on intriguing studies that predict potential un-identifying side-effects and suggest how we can avoid drug side-effects by the removal of some distinguished chemical structures. [ABSTRACT FROM AUTHOR]

Motivation: To minimize the accelerating amount of time invested on the biomedical literature search, numerous approaches for automated knowledge extraction have been proposed. Relation extraction is one such task where semantic relations between the entities are identified from the free text. In the biomedical domain, extraction of regulatory pathways, metabolic processes, adverse drug reaction or disease models necessitates knowledge from the individual relations, for example, physical or regulatory interactions between genes, proteins, drugs, chemical, disease or phenotype. Results: In this paper, we study the relation extraction task from three major biomedical and clinical tasks, namely drug-drug interaction, protein-protein interaction, and medical concept relation extraction. Towards this, we model the relation extraction problem in a multi-task learning (MTL)framework, and introduce for the first time the concept of structured self-attentive network complemented with the adversarial learning approach for the prediction of relationships from the biomedical and clinical text. The fundamental notion of MTL is to simultaneously learn multiple problems together by utilizing the concepts of the shared representation. Additionally, we also generate the highly efficient single task model which exploits the shortest dependency path embedding learned over the attentive gated recurrent unit to compare our proposed MTL models. The framework we propose significantly improves over all the baselines (deep learning techniques)and single-task models for predicting the relationships, without compromising on the performance of all the tasks. [ABSTRACT FROM AUTHOR]

RNA-binding proteins (RBPs) have a significant role in various regulatory tasks. However, the mechanism by which RBPs identify the subsequence target RNAs is still not clear. In recent years, several machine and deep learning-based computational models have been proposed for understanding the binding preferences of RBPs. These methods required integrating multiple features with raw RNA sequences such as secondary structure and their performances can be further improved. In this paper, we propose an efficient and simple convolution neural network, RBPCNN, that relies on the combination of the raw RNA sequence and evolutionary information. We show that conservation scores (evolutionary information) for the RNA sequences can significantly improve the overall performance of the proposed predictor. In addition, the automatic extraction of the binding sequence motifs can enhance our understanding of the binding specificities of RBPs. The experimental results show that RBPCNN outperforms significantly the current state-of-the-art methods. More specifically, the average area under the receiver operator curve was improved by 2.67 percent and the mean average precision was improved by 8.03 percent. The datasets and results can be downloaded from https://home.jbnu.ac.kr/NSCL/RBPCNN.htm. [ABSTRACT FROM AUTHOR]

Extra-cellular molecules trigger a response inside the cell by initiating a signal at special membrane receptors (i.e.,sources), which is then transmitted to reporters (i.e., targets) through various chains of interactions among proteins. Understanding whether such a signal can reach from membrane receptors to reporters is essential in studying the cell response to extra-cellular events. This problem is drastically complicated due to the unreliability of the interaction data. In this paper, we develop a novel method, called PReach (Probabilistic Reachability), that precisely computes the probability that a signal can reach from a given collection of receptors to a given collection of reporters when the underlying signaling network is uncertain. This is a very difficult computational problem with no known polynomial-time solution. PReach represents each uncertain interaction as a bi-variate polynomial.It transforms the reachability problem to a polynomial multiplication problem. We introduce novel polynomial collapsing operators that associate polynomial terms with possible paths between sources and targets as well as the cuts that separate sources from targets. These operators significantly shrink the number of polynomial terms and thus the running time. PReach has much better timecomplexity than the recent solutions for this problem. Our experimental results on real data sets demonstrate that this improvement leads to orders of magnitude of reduction in the running time over the most recent methods. Availability: All the data sets used, the software implemented and the alignments found in this paper are available at http://bioinformatics.cise.ufl.edu/PReach/. [ABSTRACT FROM PUBLISHER]

A transistor-based biosensor with high sensitivity is demonstrated in this paper. The sensor is composed of a reusable In–Ga–ZnO (IGZO)-thin-film transistor (TFT) array wire connected to an external sensing pool. The TFT acts as an electrical charge transducer as well as the signal readout device. Contrast to typical approachesofemploying parameters, such as transconductance, threshold voltage, or current change as the benchmark for sensitivity, we develop a model to extract the corresponding electrical changes after introducing analytes so as tomitigate device-to-device sensing variations. Using Epstein–Barr nuclear antigen-1 (EBNA-1) antibody as the example of target analyte, the IGZO-TFT biosensors are able to selectively detect 10 pg/mL of EBNA-1 antibody in the phosphate-buffered saline solution. The measurement results were cross verifiedwith conventional enzyme-linked immunosorbent assay (ELISA). Our approach is four orders of magnitude better than the ELISA. [ABSTRACT FROM AUTHOR]

Molecular motor networks (MMNs) are networks constructed from molecular motors to enable nanomachines to perform coordinated tasks of sensing, computing, and actuation at the nano- and micro- scales. Living cells are naturally enabled with this same mechanism to establish point-to-point communication between different locations inside the cell. Similar to a railway system, the cytoplasm contains an intricate infrastructure of tracks, named microtubules, interconnecting different internal components of the cell. Motor proteins, such as kinesin and dynein, are able to travel along these tracks directionally, carrying with them large molecules that would otherwise be unreliably transported across the cytoplasm using free diffusion. Molecular communication has been previously proposed for the design and study of MMNs. However, the topological aspects of MMNs, including the effects of branches, have been ignored in the existing studies. In this paper, a physical end-to-end model for MMNs is developed, considering the location of the transmitter node, the network topology, and the receiver nodes. The end-to-end gain and group delay are considered as the performance measures, and analytical expressions for them are derived. The analytical model is validated by Monte-Carlo simulations and the performance of MMNs is analyzed numerically. It is shown that, depending on their nature and position, MMN nodes create impedance effects that are critical for the overall performance. This model could be applied to assist the design of artificial MMNs and to study cargo transport in neurofilaments to elucidate brain diseases related to microtubule jamming. [ABSTRACT FROM PUBLISHER]

Structural flexibility plays an essential role in many biological processes. B-factor is an important indicator to measure the flexibility of protein or RNA structures. Many methods were developed to predict protein B-factors, but few studies have been done for RNA B-factor prediction. In this paper, we proposed a new method RNAbval to predict RNA B-factors using random forest. The method was developed using a comprehensive set of features, including the sequence profile and predicted solvent accessibility. RNAbval achieved an improvement of 9.2-20.5 percent over the state-of-the-art method on two benchmark test datasets. The proposed method is available at http://yanglab.nankai.edu.cn/RNAbval/. [ABSTRACT FROM AUTHOR]

Next-generation sequencing techniques provide us with an opportunity for generating sequenced proteins and identifying the biological families and functions of these proteins. However, compared with identified proteins, uncharacterized proteins consist of a notable percentage of the overall proteins in the bioinformatics research field. Traditional family classification methods often devote themselves to extracting N-Gram features from sequences while ignoring motif information as well as affinity information between motifs and adjacent amino acids. Previous clustering-based algorithms have typically been used to define protein features with domain knowledge and annotate protein families based on extensive data samples. In this paper, we apply CNN based amino acid representation learning with limited characterized proteins to explore the performances of annotated protein families by taking into account the amino acid location information. Additionally, we apply the method to all reviewed protein sequences with their families retrieved from the UniProt database to evaluate our approach. Last but not least, we verify our model using those unreviewed protein records, which is typically ignored by other methods. [ABSTRACT FROM AUTHOR]

With its potential of single cell specificity, optogenetics has made the investigation into the brain circuits more controllable. Closed loop optogenetic brain stimulation enhances the efficacy of the stimulation by adjusting the stimulation parameters based on direct feedback from the target area of the brain. It combines the principles of genetics, physiology, electrical engineering, optics, signal processing and control theory to create an efficient brain stimulation system. To read the underlying neuronal condition from the electrical activity of neurons, a sensor, sensor interface circuit, and signal conditioning are needed. Also, efficient feature extraction, classification, and control algorithms should be in place to interpret and use the sensed data for closing the feedback loop. Finally, a stimulation circuitry is required to effectively control a light source to deliver light based stimulation according to the feedback signal. Thus, the backbone to a functioning closed loop optogenetic brain stimulation device is a well-built electronic circuitry for sensing and processing of brain signals, running efficient signal processing and control algorithm, and delivering timed light stimulations. This paper presents a review of electronic and software concepts and components used in recent closed-loop optogenetic devices based on neuro-electrophysiological reading and an outlook on the future design possibilities with the aim of providing a compact and easy reference for developing closed loop optogenetic brain stimulation devices. [ABSTRACT FROM AUTHOR]

In this paper, we study the acceleration of applications that identify all the occurrences of thousands of string-patterns in an input data-stream using the Automata Processor (AP). For this evaluation, we use two applications from two fields, namely, cybersecurity and bioinformatics. The first application, called Fast-SNAP, scans network data for 4312 signatures of intrusion derived from the popular open-source Snort database. Using the resources of a single AP-board, Fast-SNAP can scan for all these signatures at 1 Gbps. The second application, called PROTOMATA, looks for all the occurrences of 1,309 motifs from the PROSITE database in protein sequences. PROTOMATA is up to 68 times faster than the state-of-the-art CPU implementation. As a comparison, we emulate the execution of the same NFAs by programming FPGAs using state-of-the-art techniques. We find that the performance derived by using the resources of a single AP-board, which houses 32 AP-chips, is comparable to that of the resources of five to six large FPGAs. The design techniques used in this paper are generic and may be applicable to the development of similar applications on the AP. [ABSTRACT FROM AUTHOR]

The prediction of Drug-Target Interaction (DTI) is an important research direction in bioinformatics as it greatly shortens the development cycle of new drugs. State-of-the-art computational methods for DTI prediction adopt a binary classification framework. The supervision is incomplete, i.e. only a small amount of DTIs are known and treated as positive instances, while the rest are unknown and treated as negative. Two severe problems occur in such a framework: (1) the number of negative samples is overwhelming and (2) a negative label cannot rule out the possibility of a positive drug-target interaction. In this paper, we address the problem of learning from incomplete labels in DTI prediction. The key assumption here is that labels are missing not at random. For example, negative DTI labels are more likely to be missing because biomedical researchers prioritize to study DTIs that are more likely to be positive. We introduce a novel probabilistic model, factorization with non-random missing labels (FNML). It models the generative process for the DTI labels (i.e. the labels are positive or negative) and responses (i.e. the labels are observed or missing). In particular, the probability of observing or missing a label is associated with the sign of the label. In order to further reduce prediction variance and improve prediction accuracy on highly imbalanced DTI datasets, we present FNML-EN, an ensemble scheme which is designed specifically for FNML model. We conduct comprehensive experiments on the latest DTI database, demonstrating the superior and robust performance of the proposed models. [ABSTRACT FROM AUTHOR]

Among the different scientific domains where metaheuristics find applicability, bioinformatics represents a particularly challenging field due to the multiple complexity factors involved in the processing of biological data. In this context, the exploration of protein sequence data is remarkably increasing the temporal demands of such biological problems, thus motivating the interest in investigating new approaches that effectively combine bioinspired metaheuristics and parallelism. This paper addresses the reconstruction of ancestral relationships from amino acid sequences by using a multiobjective approach based on the shuffled frog-leaping optimization technique. Due to the inherent parallel nature of this approach, we define different parallel schemes aimed at exploiting the computing capabilities of modern cluster platforms. The experiments performed in five real datasets give account of the relevance of using parallelism-aware metaheuristic designs, as well as the need to consider both parallel performance and solution quality when tackling such difficult optimization scenarios. [ABSTRACT FROM AUTHOR]

The outbreak of the Ebola virus in recent years has resulted in numerous research initiatives to seek new solutions to contain the virus. A number of approaches that have been investigated include new vaccines to boost the immune system. An alternative post-exposure treatment is presented in this paper. The proposed approach for clearing the Ebola virus can be developed through a microfluidic attenuator, which contains the engineered bacteria that traps Ebola flowing through the blood onto its membrane. The paper presents the analysis of the chemical binding force between the virus and a genetically engineered bacterium considering the opposing forces acting on the attachment point, including hydrodynamic tension and drag force. To test the efficacy of the technique, simulations of bacterial motility within a confined area to trap the virus were performed. More than 60 percent of the displaced virus could be collected within 15 minutes. While the proposed approach currently focuses on in vitro environments for trapping the virus, the system can be further developed into a future treatment system whereby blood can be cycled out of the body into a microfluidic device that contains the engineered bacteria to trap viruses. [ABSTRACT FROM AUTHOR]

Diverse applications involving complicated data objects such as proteins and images are solved by applying multi-instance learning (MIL) algorithms. However, few MIL algorithms can deal with problems in an open and dynamic environment, where new categories of samples emerge. In this type of emerging novel class setting, algorithms should be able to not only classify the samples from the observed classes accurately, but also recognize the samples from the novel class. In this paper, we focus on the Multi-Instance learning with Emerging Novel class (MIEN) problem, and formulate MIEN from a metric learning perspective. We extract key instances to form the “super-bag” for each observed class, and non-key instances from all the observed classes to form a “meta super-bag”. Based on these super-bags, we propose the MIEN-metric method to learn discriminative metrics for classifying MIL bags from the observed classes and recognizing bags from the novel class. Experimental results of diverse domains, e.g., biological function annotation, text categorization, and object-centric/scene-centric image classification, show MIEN-metric outperforms other baseline methods significantly when the novel class emerges. Meanwhile, MIEN-metric is comparable with state-of-the-art MIL algorithms for binary classification in the traditional MIL setting. [ABSTRACT FROM AUTHOR]

In conventional molecular communication (MC) systems, the signaling molecules used for information transmission are stored, released, and then replenished by a transmitter (TX). However, the replenishment of signaling molecules at the TX is challenging in practice. Furthermore, in most envisioned MC applications, e.g., in the medical field, it is not desirable to insert the TX into the MC system, as this might impair natural biological processes. In this paper, we propose the concept of media modulation based MC where the TX is placed outside the channel and utilizes signaling molecules already present inside the system. The signaling molecules can assume different states which can be switched by external stimuli. Hence, in media modulation based MC, the TX modulates information into the state of the signaling molecules. In particular, we exploit the group of photochromic molecules, which undergo light-induced reversible state transitions, for media modulation. We study the usage of these molecules for information transmission in a three-dimensional duct system, which contains an eraser, a TX, and a receiver for erasing, writing, and reading of information via external light, respectively. We develop a statistical model for the received signal which accounts for the distribution of the signaling molecules in the system, the initial states of the signaling molecules, the reliability of the state control mechanism, the randomness of irrepressible, spontaneous state switching, and the randomness of molecule propagation. We adopt a maximum likelihood detector and show that it can be reduced to a threshold based detector. Furthermore, we derive analytical expressions for the optimal threshold value and the resulting bit error rate (BER), respectively. Both the statistical model and BER results are verified by computer simulations. Our results reveal that media modulation enables reliable information transmission, validating it as a promising alternative to MC based on molecule emitting TXs. [ABSTRACT FROM AUTHOR]

Artificial gene regulatory networks (GRNs) are biologically inspired dynamical systems used to control various kinds of agents, from the cells in developmental models to embodied robot swarms. Most recent work uses a genetic algorithm (GA) or an evolution strategy in order to optimize the network for a specific task. However, the empirical performances of these algorithms are unsatisfactory. This paper presents an algorithm that primarily exploits a network distance metric, which allows genetic similarity to be used for speciation and variation of GRNs. This algorithm, inspired by the successful neuroevolution of augmenting topologies algorithm’s use in evolving neural networks and compositional pattern-producing networks, is based on a specific initialization method, a crossover operator based on gene alignment, and speciation based upon GRN structures. We demonstrate the effectiveness of this new algorithm by comparing our approach both to a standard GA and to evolutionary programming on four different experiments from three distinct problem domains, where the proposed algorithm excels on all experiments. [ABSTRACT FROM AUTHOR]

Compression schemes for advanced data structures have become a central modern challenge. Information theory has traditionally dealt with conventional data such as text, images, or video. In contrast, most data available today is multitype and context-dependent. To meet this challenge, we have recently initiated a systematic study of advanced data structures such as unlabeled graphs. In this paper, we continue this program by considering trees with statistically correlated vertex names. Trees come in many forms, but here we deal with binary plane trees (where order of subtrees matters) and their non-plane version (where order of subtrees doesn’t matter). Furthermore, we assume that each name is generated by a known memoryless source (horizontal independence), but a symbol of a vertex name depends in a Markovian sense on the corresponding symbol of the parent vertex name (vertical Markovian dependency). Such a model is closely connected to models of phylogenetic trees. While in general, the problem of multimodal compression and associated analysis can be extremely complicated, we find that in this natural setting, both the entropy analysis and optimal compression are analytically tractable. We evaluate the entropy for both types of trees. For the plane case, with or without vertex names, we find that a simple two-stage compression scheme is both efficient and optimal. We then present efficient and optimal compression algorithms for the more complicated non-plane case. [ABSTRACT FROM AUTHOR]

This paper presents a systematic study of bovine serum albumin (BSA) conjugation on the amine-functionalized magnetic nanoparticles (MNPs) and the effects of various experimental parameters on the conjugation process. The amine-functionalized Fe2O3 NPs with silica shell were synthesized through surface modification. The BSA conjugation on the amine-functionalized Fe2O3 NPs was achieved through covalent binding via carbodiimide activation. Morphology and magnetic properties of the nanoparticles were investigated. The influence of reaction time, the initial protein concentration, and the temperature on BSA conjugation was studied. The increased reaction time promoted the conjugation of BSA on the Fe2O3 NPs and finally reached the saturation at 43.4 mg/g. The initial BSA concentration can increase the amount of conjugated BSA. The temperature exhibited no significant effect on the conjugation process. The results are useful for designing effective fabrication strategy for protein-conjugated nanomaterials. [ABSTRACT FROM AUTHOR]

An in-depth exploration of gene prognosis using different methodologies aids in understanding various biological regulations of genes in disease pathobiology and molecular functions. Interpreting gene functions at biological and molecular levels remains a daunting yet crucial task in domains such as drug design, personalized medicine, and next-generation diagnostics. Recent advancements in omics technologies have produced diverse heterogeneous genomic datasets like micro-array gene expression, miRNA expression, DNA sequence, 3D structures, which are significant resources for understanding the gene functions. In this paper, we propose a novel self-attention based deep multi-modal model, named DeePROG, for the prognosis of disease affected genes based on heterogeneous omics data. We use three NCBI datasets covering three modalities, namely gene expression profile, the underlying DNA sequence, and the 3D protein structures. To extract useful features from each modality, we develop several context-specific deep learning models. Besides, we develop three attention-based deep bi-modal architectures along with DeePROG to leverage the prognosis of the underlying biomedical data. We assess the performance of the models’ in terms of computational assessment of function annotation (CAFA2) metrics. Moreover, we analyze the results in terms of receiver operating characteristics (ROC) curve in high-class imbalance data setting and perform statistical significance tests in terms of Welch's t-test. Experiment results show that DeePROG significantly outperforms baseline models across in terms of performance metrics. The source code and all preprocessed datasets used in this study are available at https://github.com/duttaprat/DeePROG. [ABSTRACT FROM AUTHOR]

Event sequences are central to the analysis of data in domains that range from biology and health, to logfile analysis and people's everyday behavior. Many visualization tools have been created for such data, but people are error-prone when asked to judge the similarity of event sequences with basic presentation methods. This article describes an experiment that investigates whether local and global alignment techniques improve people's performance when judging sequence similarity. Participants were divided into three groups (basic versus local versus global alignment), and each participant judged the similarity of 180 sets of pseudo-randomly generated sequences. Each set comprised a target, a correct choice and a wrong choice. After training, the global alignment group was more accurate than the local alignment group (98 versus 93 percent correct), with the basic group getting 95 percent correct. Participants’ response times were primarily affected by the number of event types, the similarity of sequences (measured by the Levenshtein distance) and the edit types (nine combinations of deletion, insertion and substitution). In summary, global alignment is superior and people's performance could be further improved by choosing alignment parameters that explicitly penalize sequence mismatches. [ABSTRACT FROM AUTHOR]

Objective: To develop a new class of emulsions using a protein-based emulsifier as the coupling fluid for microwave imaging systems. Methods: In this paper, we provide a theoretical basis for engineering shelf-stable dielectric fluids, a step-by-step formulation method, and measurements of complex dielectric properties in the frequency range of 0.5-3 GHz, which can be applicable for many of the recent microwave imaging systems. Results: This medium was primarily designed for long-term stability while providing a controllable range of complex dielectric permittivities given different fractions of its constituents. Consequently, this emulsion shows dielectric stability in open air throughout a 7-day experiment and temperature insensitivity over the range of 0 ${\,^\circ }$ C to 60 ${^\circ }$. Conclusions: This control over dielectric permittivity enables formulations that tune the background-to-target contrast to the linearizable regime of iterative inverse scattering algorithms. Accordingly, the emulsion conductivity can also be controlled and reduced to maintain the required signal-to-noise ratio within the dynamic range of the imaging system. The new formulation overcomes the practical challenges of engineering coupling fluids for microwave imaging systems, e.g., temporal stability, non-toxic, low sensitivity to temperature variation, and easy formulation from readily available and inexpensive materials. Significance: The achieved properties associated with this new fluid are of particular benefit to microwave imaging systems used in thermal therapy monitoring. [ABSTRACT FROM AUTHOR]

Protein-protein interaction (PPI) is an important field in bioinformatics which helps in understanding diseases and devising therapy. PPI aims at estimating the similarity of protein sequences and their common regions. STRIKE was introduced as a PPI algorithm which was able to achieve reasonable improvement over existing PPI prediction methods. Although it consumes a lower execution time than most of other state-of the-art PPI prediction methods, its compute-intensive nature and the large volume of protein sequences in protein databases necessitate further time acceleration. In this paper, we develop hardware accelerator designs for the STRIKE algorithm. Results indicate that the weighted STRIKE accelerator execution times are about 10x longer than the unweighted STRIKE accelerator execution times. To further accelerate the performance of the weighted STRIKE, a parallel module accelerator organization duplicating the weighted STRIKE modules is introduced, achieving near linear speedups for long sequences of 100 or more characters. As demonstrated by Verilog simulations and FPGA runs, the weighted STRIKE module accelerator exhibits three orders of magnitude speed improvement over multi-core and cluster computers. Much higher speedups are possible with the parallel module accelerator. [ABSTRACT FROM AUTHOR]

Alternative splicing enables a gene translating into different isoforms and into the corresponding proteoforms, which actually accomplish various biological functions of a living body. Isoform-isoform interactions (IIIs) provide a higher resolution interactome to explore the cellular processes and disease mechanisms than the canonically studied protein-protein interactions (PPIs), which are often recorded at the coarse gene level. The knowledge of IIIs is critical to map pathways, understand protein complexity and functional diversity, but the known IIIs are very scanty. In this paper, we propose a deep learning based method called DeepIII to systematically predict genome-wide IIIs by integrating diverse data sources, including RNA-seq datasets of different human tissues, exon array data, domain-domain interactions (DDIs) of proteins, nucleotide sequences and amino acid sequences. Particularly, DeepIII fuses these data to learn the representation of isoform pairs with a four-layer deep neural networks, and then performs binary classification on the learnt representation to achieve the prediction of IIIs. Experimental results show that DeepIII achieves a superior prediction performance to the state-of-the-art solutions and the III network constructed by DeepIII gives more accurate isoform function prediction. Case studies further confirm that DeepIII can differentiate the individual interaction partners of different isoforms spliced from the same gene. The code and datasets of DeepIII are available at http://mlda.swu.edu.cn/codes.php?name=DeepIII. [ABSTRACT FROM AUTHOR]

In real-world graphs such as social networks, Semantic Web and biological networks, each vertex usually contains rich information, which can be modeled by a set of tokens or elements. In this paper, we study a subgraph matching with set similarity (SMS$^2$ ) query over a large graph database, which retrieves subgraphs that are structurally isomorphic to the query graph, and meanwhile satisfy the condition of vertex pair matching with the (dynamic) weighted set similarity. To efficiently process the SMS $^2$ query, this paper designs a novel lattice-based index for data graph, and lightweight signatures for both query vertices and data vertices. Based on the index and signatures, we propose an efficient two-phase pruning strategy including set similarity pruning and structure-based pruning, which exploits the unique features of both (dynamic) weighted set similarity and graph topology. We also propose an efficient dominating-set-based subgraph matching algorithm guided by a dominating set selection algorithm to achieve better query performance. Extensive experiments on both real and synthetic datasets demonstrate that our method outperforms state-of-the-art methods by an order of magnitude. [ABSTRACT FROM AUTHOR]

Protein tertiary structure prediction is an important open challenge in bioinformatics and requires effective methods to accurately evaluate the quality of protein 3-D models generated computationally. Many quality assessment (QA) methods have been proposed over the past three decades. However, the accuracy or robustness is unsatisfactory for practical applications. In this paper, two new heuristic QA methods are proposed: MUfoldQA_S and MUfoldQA_C. The MUfoldQA_S is a quasi-single-model QA method that assesses the model quality based on the known protein structures with similar sequences. This algorithm can be directly applied to protein fragments without the necessity of building a full structural model. A BLOSUM-based heuristic is also introduced to help differentiate accurate templates from poor ones. In MUfoldQA_C, the ideas from MUfoldQA_S were combined with the consensus approach to create a multi-model QA method that could also utilize information from existing reference models and have demonstrated improved performance. Extensive experimental results of these two methods have shown significant improvement over existing methods. In addition, both methods have been blindly tested in the CASP12 world-wide competition in the protein structure prediction field and ranked as top performers in their respective categories. [ABSTRACT FROM AUTHOR]

The three-dimensional structures populated by a protein molecule determine to a great extent its biological activities. The rich information encoded by protein structure on protein function continues to motivate the development of computational approaches for determining functionally-relevant structures. The majority of structures generated in silico are not relevant. Discriminating relevant/native protein structures from non-native ones is an outstanding challenge in computational structural biology. Inherently, this is a recognition problem that can be addressed under the umbrella of machine learning. In this paper, based on the premise that near-native structures are effectively anomalies, we build on the concept of anomaly detection in machine learning. We propose methods that automatically select relevant subsets, as well as methods that select a single structure to offer as prediction. Evaluations are carried out on benchmark datasets and demonstrate that the proposed methods advance the state of the art. The presented results motivate further building on and adapting concepts and techniques from machine learning to improve recognition of near-native structures in protein structure prediction. [ABSTRACT FROM AUTHOR]

This article considers implementation of artificial neural networks (ANNs) using molecular computing and DNA based on fractional coding. Prior work had addressed molecular two-layer ANNs with binary inputs and arbitrary weights. In prior work using fractional coding, a simple molecular perceptron that computes sigmoid of scaled weighted sum of the inputs was presented where the inputs and the weights lie between $[-1,1]$. Even for computing the perceptron, the prior approach suffers from two major limitations. First, it cannot compute the sigmoid of the weighted sum, but only the sigmoid of the scaled weighted sum. Second, many machine learning applications require the coefficients to be arbitrarily positive and negative numbers that are not bounded between $[-1,1]$ ; such numbers cannot be handled by the prior perceptron using fractional coding. This paper makes four contributions. First molecular perceptrons that can handle arbitrary weights and can compute sigmoid of the weighted sums are presented. Thus, these molecular perceptrons are ideal for regression applications and multi-layer ANNs. A new molecular divider is introduced and is used to compute $sigmoid(ax)$ where $a>1$. Second, based on fractional coding, a molecular artificial neural network (ANN) with one hidden layer is presented. Third, a trained ANN classifier with one hidden layer from seizure prediction application from electroencephalogram is mapped to molecular reactions and DNA and their performances are presented. Fourth, molecular activation functions for rectified linear unit (ReLU) and softmax are also presented. [ABSTRACT FROM AUTHOR]