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Furthermore, in terms of protein identification, Xu et al. concentrated on the study of antioxidant protein identification; they proposed a machine learning method, SeqSVM, to predict antioxidant proteins through extracted sequence features [[10]]. The identification of special protein or RNA molecules via computational methods is of great importance in understanding their biological functions and developing new treatments for diseases. Seven papers focus on describing protein function prediction or protein identification, which include the prediction of signal peptides in proteins, protein hydroxylation site prediction, protein-protein interaction (PPI) prediction, and protein identification. [Extracted from the article]

Aiming at the melt splashing behavior in the smelting process of an oxygen-enriched side-blowing furnace, the volume of fluid model and the realizable k − ε turbulence model are coupled and simulated. The effects of different operating parameters (injection velocity, immersion depth, liquid level) on splash height are explored, and the simulation results are verified by water model experiments. The results show that the bubbles with residual kinetic energy escape to the slag surface and cause slag splashing. The slag splashing height gradually increases with the increase in injection velocity, and the time-averaged splashing height reaches 1.01 m when the injection speed is 160 m/s. Increasing the immersion depth of the lance, and the slag splashing height gradually decreases. When the immersion depth is 0.12 m, the time-averaged splashing height is 0.85 m. Increasing the liquid level is beneficial to reduce the splash height, when the liquid level is 2.7 m, the splash height reduces to 0.77 m. With the increase in the liquid level, the slag splashing height gradually decreases, and the time-averaged splashing height is 0.77 m when the initial liquid level is 2.7 m. [ABSTRACT FROM AUTHOR]

Computational identification of special protein molecules is a key issue in understanding protein function. It can guide molecular experiments and help to save costs. I assessed 18 papers published in the special issue of Int. J. Mol. Sci., and also discussed the related works. The computational methods employed in this special issue focused on machine learning, network analysis, and molecular docking. New methods and new topics were also proposed. There were in addition several wet experiments, with proven results showing promise. I hope our special issue will help in protein molecules identification researches. [ABSTRACT FROM AUTHOR]

By integrating biological and bioinformatics data, Turek et al. (2023) [[21]] performed a genome assembly on the B10v3 cucumber genome and presented a well-organized and annotated reference genome of cucumber, contributing to better understanding of the cucumber genome. Using genome-wide classification and functional annotation, Cenci et al. (2022) [[18]] effectively characterized a large gene family across multiple species and established a classification framework for gene functional transfer, enabling a better understanding of the evolutionary history of one gene. In addition, several papers explored functional genomics of plant genomes, such as gene functional annotation and the development of functional genomics tools. Comparative genomics and functional genomics are two basic branches of plant genomics. [Extracted from the article]

Simple Summary: Pholcus is the most diverse spider genus in Pholcidae, and is widely distributed in the Palaearctic, Indo-Malayan, Afrotropical, and Australasian Regions. Previously, the Pholcus spiders have not been recorded from the Lüliang Mountains of North China. We undertook an expedition there for the first time. Phylogenetic analyses of DNA sequence data from four gene fragments (COI, H3, wnt, 28S) suggested that Pholcus from the Lüliang Mountains were grouped into nine well-supported clades. We adopted an integrative approach, including morphology and four methods of molecular species delimitation (ABGD, GMYC, bPTP, and BPP), to investigate species boundaries. Such analyses identified the nine clades as nine separate species, of which eight are new to science. All of them belong to the P. phungiformes species group. Spiders of the genus Pholcus were collected for the first time during an expedition to the Lüliang Mountains in Shanxi Province, North China. Phylogenetic analyses of DNA sequence data from COI, H3, wnt, and 28S genes allowed us to group them into nine well-supported clades. We used morphology and four methods of molecular species delimitation, namely Automatic Barcode Gap Discovery (ABGD), the Generalized Mixed Yule Coalescent (GMYC), Bayesian Poisson Tree Processes (bPTP), and Bayesian Phylogenetics and Phylogeography (BPP), to investigate species boundaries. These integrative taxonomic analyses identified the nine clades as nine distinct species, comprising Pholcus luya Peng & Zhang, 2013 and eight other species new to science: Pholcus jiaocheng sp. nov., Pholcus linfen sp. nov., Pholcus lishi sp. nov., Pholcus luliang sp. nov., Pholcus wenshui sp. nov., Pholcus xiangfen sp. nov., Pholcus xuanzhong sp. nov., and Pholcus zhongyang sp. nov. The species occur in geographic proximity and show many morphological similarities. All of them belong to the P. phungiformes species group. The records from the Lüliang Mountains represent the westernmost distribution limit of this species group. [ABSTRACT FROM AUTHOR]

Biocomputing and synthetic biology have been two of the most exciting emerging fields in recent years. A gene co-expression network is constructed by using the differentially expressed genes of each cell subpopulation, identified via the use of spectral clustering. Then, in the constructed gene co-expression network, the dense subgraphs are learnt to detect the interactive gene groups. A real cancer scRNA-seq dataset is used for testing the proposed framework to detect interactive gene groups of different cancer subtypes, and results show that different gene co-expression networks and interactive gene groups with different functional enrichment are presented in different subtypes. [Extracted from the article]

Recent advances in single-cell sequencing assays for the transposase-accessibility chromatin (scATAC-seq) technique have provided cell-specific chromatin accessibility landscapes of cis-regulatory elements, providing deeper insights into cellular states and dynamics. However, few research efforts have been dedicated to modeling the relationship between regulatory grammars and single-cell chromatin accessibility and incorporating different analysis scenarios of scATAC-seq data into the general framework. To this end, we propose a unified deep learning framework based on the ProdDep Transformer Encoder, dubbed PROTRAIT, for scATAC-seq data analysis. Specifically motivated by the deep language model, PROTRAIT leverages the ProdDep Transformer Encoder to capture the syntax of transcription factor (TF)-DNA binding motifs from scATAC-seq peaks for predicting single-cell chromatin accessibility and learning single-cell embedding. Based on cell embedding, PROTRAIT annotates cell types using the Louvain algorithm. Furthermore, according to the identified likely noises of raw scATAC-seq data, PROTRAIT denoises these values based on predated chromatin accessibility. In addition, PROTRAIT employs differential accessibility analysis to infer TF activity at single-cell and single-nucleotide resolution. Extensive experiments based on the Buenrostro2018 dataset validate the effeteness of PROTRAIT for chromatin accessibility prediction, cell type annotation, and scATAC-seq data denoising, therein outperforming current approaches in terms of different evaluation metrics. Besides, we confirm the consistency between the inferred TF activity and the literature review. We also demonstrate the scalability of PROTRAIT to analyze datasets containing over one million cells. [ABSTRACT FROM AUTHOR]

Regulators in gene regulatory networks (GRNs) are crucial for identifying cell states. However, GRN inference based on scRNA-seq data has several problems, including high dimensionality and sparsity, and requires more label data. Therefore, we propose a meta-learning GRN inference framework to identify regulatory factors. Specifically, meta-learning solves the parameter optimization problem caused by high-dimensional sparse data features. In addition, a few-shot solution was used to solve the problem of lack of label data. A structural equation model (SEM) was embedded in the model to identify important regulators. We integrated the parameter optimization strategy into the bi-level optimization to extract the feature consistent with GRN reasoning. This unique design makes our model robust to small-scale data. By studying the GRN inference task, we confirmed that the selected regulators were closely related to gene expression specificity. We further analyzed the GRN inferred to find the important regulators in cell type identification. Extensive experimental results showed that our model effectively captured the regulator in single-cell GRN inference. Finally, the visualization results verified the importance of the selected regulators for cell type recognition. [ABSTRACT FROM AUTHOR]

Low complexity regions (LCRs) in proteins are characterized by amino acid frequencies that differ from the average. These regions evolve faster and tend to be less conserved between homologs than globular domains. They are not common in bacteria, as compared to their prevalence in eukaryotes. Studying their conservation could help provide hypotheses about their function. To obtain the appropriate evolutionary focus for this rapidly evolving feature, here we study the conservation of LCRs in bacterial strains and compare their high variability to the closeness of the strains. For this, we selected 20 taxonomically diverse bacterial species and obtained the completely sequenced proteomes of two strains per species. We calculated all orthologous pairs for each of the 20 strain pairs. Per orthologous pair, we computed the conservation of two types of LCRs: compositionally biased regions (CBRs) and homorepeats (polyX). Our results show that, in bacteria, Q-rich CBRs are the most conserved, while A-rich CBRs and polyA are the most variable. LCRs have generally higher conservation when comparing pathogenic strains. However, this result depends on protein subcellular location: LCRs accumulate in extracellular and outer membrane proteins, with conservation increased in the extracellular proteins of pathogens, and decreased for polyX in the outer membrane proteins of pathogens. We conclude that these dependencies support the functional importance of LCRs in host–pathogen interactions. [ABSTRACT FROM AUTHOR]

Some drugs can be used to treat multiple diseases, suggesting potential patterns in drug treatment. Determination of drug treatment patterns can improve our understanding of the mechanisms of drug action, enabling drug repurposing. A drug can be associated with a multilayer tissue-specific protein–protein interaction (TSPPI) network for the diseases it is used to treat. Proteins usually interact with other proteins to achieve functions that cause diseases. Hence, studying drug treatment patterns is similar to studying common module structures in multilayer TSPPI networks. Therefore, we propose a network-based model to study the treatment patterns of drugs. The method was designated SDTP (studying drug treatment pattern) and was based on drug effects and a multilayer network model. To demonstrate the application of the SDTP method, we focused on analysis of trichostatin A (TSA) in leukemia, breast cancer, and prostate cancer. We constructed a TSPPI multilayer network and obtained candidate drug-target modules from the network. Gene ontology analysis provided insights into the significance of the drug-target modules and co-expression networks. Finally, two modules were obtained as potential treatment patterns for TSA. Through analysis of the significance, composition, and functions of the selected drug-target modules, we validated the feasibility and rationality of our proposed SDTP method for identifying drug treatment patterns. In summary, our novel approach used a multilayer network model to overcome the shortcomings of single-layer networks and combined the network with information on drug activity. Based on the discovered drug treatment patterns, we can predict the potential diseases that the drug can treat. That is, if a disease-related protein module has a similar structure, then the drug is likely to be a potential drug for the treatment of the disease. [ABSTRACT FROM AUTHOR]

Gene fusion structure is a class of common somatic mutational events in cancer genomes, which are often formed by chromosomal mutations. Identifying the driver gene(s) in a fusion structure is important for many downstream analyses and it contributes to clinical practices. Existing computational approaches have prioritized the importance of oncogenes by incorporating prior knowledge from gene networks. However, different methods sometimes suffer different weaknesses when handling gene fusion data due to multiple issues such as fusion gene representation, network integration, and the effectiveness of the evaluation algorithms. In this paper, Synstable Fusion (SYN), an algorithm for computationally evaluating the fusion genes, is proposed. This algorithm uses network-based strategy by incorporating gene networks as prior information, but estimates the driver genes according to the destructiveness hypothesis. This hypothesis balances the two popular evaluation strategies in the existing studies, thereby providing more comprehensive results. A machine learning framework is introduced to integrate multiple networks and further solve the conflicting results from different networks. In addition, a synchronous stability model is established to reduce the computational complexity of the evaluation algorithm. To evaluate the proposed algorithm, we conduct a series of experiments on both artificial and real datasets. The results demonstrate that the proposed algorithm performs well on different configurations and is robust when altering the internal parameter settings. [ABSTRACT FROM AUTHOR]

P-glycoprotein (P-gp), a membrane-bound transporter, can eliminate xenobiotics by transporting them out of the cells or blood–brain barrier (BBB) at the expense of ATP hydrolysis. Thus, P-gp mediated efflux plays a pivotal role in altering the absorption and disposition of a wide range of substrates. Nevertheless, the mechanism of P-gp substrate efflux is rather complex since it can take place through active transport and passive permeability in addition to multiple P-gp substrate binding sites. A nonlinear quantitative structure–activity relationship (QSAR) model was developed in this study using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to explore the perplexing relationships between descriptors and efflux ratio. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 50, r2 = 0.96, q CV 2 = 0.94, RMSE = 0.10, s = 0.10) and test set (n = 13, q2 = 0.80–0.87, RMSE = 0.21, s = 0.22). When subjected to a variety of statistical validations, the developed HSVR model consistently met the most stringent criteria. A mock test also asserted the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development. [ABSTRACT FROM AUTHOR]

Discovering the common modules that are co-expressed across various stages can lead to an improved understanding of the underlying molecular mechanisms of cancers. There is a shortage of efficient tools for integrative analysis of gene expression and protein interaction networks for discovering common modules associated with cancer progression. To address this issue, we propose a novel regularized multi-view subspace clustering (rMV-spc) algorithm to obtain a representation matrix for each stage and a joint representation matrix that balances the agreement across various stages. To avoid the heterogeneity of data, the protein interaction network is incorporated into the objective of rMV-spc via regularization. Based on the interior point algorithm, we solve the optimization problem to obtain the common modules. By using artificial networks, we demonstrate that the proposed algorithm outperforms state-of-the-art methods in terms of accuracy. Furthermore, the rMV-spc discovers common modules in breast cancer networks based on the breast data, and these modules serve as biomarkers to predict stages of breast cancer. The proposed model and algorithm effectively integrate heterogeneous data for dynamic modules. [ABSTRACT FROM AUTHOR]

The MADS-box gene family is one of the largest families in plants and plays an important roles in floral development. The MADS-box family includes the SRF-like domain and K-box domain. It is considered that the MADS-box gene family encodes a DNA-binding domain that is generally related to transcription factors, and plays important roles in regulating floral development. Our study identified 211 MADS-box protein sequences in the Zea mays proteome and renamed all the genes based on the gene annotations. All the 211 MADS-box protein sequences were coded by 98 expressed genes. Phylogenetic analysis of the MADS-box genes showed that all the family members were categorized into five subfamilies: MIKC-type, Mα, Mβ, Mγ, and Mδ. Gene duplications are regarded as products of several types of errors during the period of DNA replication and reconstruction; in our study all the 98 MADS-box genes contained 22 pairs of segmentally duplicated events which were distributed on 10 chromosomes. We compared expression data in different tissues from the female spikelet, silk, pericarp aleurone, ear primordium, leaf zone, vegetative meristem, internode, endosperm crown, mature pollen, embryo, root cortex, secondary root, germination kernels, primary root, root elongation zone, and root meristem. According to analysis of gene ontology pathways, we found a total of 41 pathways in which MADS-box genes in maize are involved. All the studies we conducted provided an overview of MADS-box gene family members in maize and showed multiple functions as transcription factors. The related research of MADS-box domains has provided the theoretical basis of MADS-box domains for agricultural applications. [ABSTRACT FROM AUTHOR]

Transcriptomic studies of mental disorders using the human brain tissues have been limited, and gene expression signatures in schizophrenia (SCZ) remain elusive. In this study, we applied three differential co-expression methods to analyze five transcriptomic datasets (three RNA-Seq and two microarray datasets) derived from SCZ and matched normal postmortem brain samples. We aimed to uncover biological pathways where internal correlation structure was rewired or inter-coordination was disrupted in SCZ. In total, we identified 60 rewired pathways, many of which were related to neurotransmitter, synapse, immune, and cell adhesion. We found the hub genes, which were on the center of rewired pathways, were highly mutually consistent among the five datasets. The combinatory list of 92 hub genes was generally multi-functional, suggesting their complex and dynamic roles in SCZ pathophysiology. In our constructed pathway crosstalk network, we found "Clostridium neurotoxicity" and "signaling events mediated by focal adhesion kinase" had the highest interactions. We further identified disconnected gene links underlying the disrupted pathway crosstalk. Among them, four gene pairs (PAK1:SYT1, PAK1:RFC5, DCTN1:STX1A, and GRIA1:MAP2K4) were normally correlated in universal contexts. In summary, we systematically identified rewired pathways, disrupted pathway crosstalk circuits, and critical genes and gene links in schizophrenia transcriptomes. [ABSTRACT FROM AUTHOR]

tRNA methyltransferase 5 (Trm5) enzyme is an S-adenosyl methionine (AdoMet)-dependent methyltransferase which methylates the G37 nucleotide at the N1 atom of the tRNA. The free form of Trm5 enzyme has three intrinsically disordered regions, which are highly flexible and lack stable three-dimensional structures. These regions gain ordered structures upon the complex formation with tRNA, also called disorder-to-order transition (DOT) regions. In this study, we performed molecular dynamics (MD) simulations of archaeal Trm5 in free and complex forms and observed that the DOT residues are highly flexible in free proteins and become stable in complex structures. The energetic contributions show that DOT residues are important for stabilising the complex. The DOT1 and DOT2 are mainly observed to be important for stabilising the complex, while DOT3 is present near the active site to coordinate the interactions between methyl-donating ligands and G37 nucleotides. In addition, mutational studies on the Trm5 complex showed that the wild type is more stable than the G37A tRNA mutant complex. The loss of productive interactions upon G37A mutation drives the AdoMet ligand away from the 37th nucleotide, and Arg145 in DOT3 plays a crucial role in stabilising the ligand, as well as the G37 nucleotide, in the wild-type complex. Further, the overall energetic contribution calculated using MMPBSA corroborates that the wild-type complex has a better affinity between Trm5 and tRNA. Overall, our study reveals that targeting DOT regions for binding could improve the inhibition of Trm5. [ABSTRACT FROM AUTHOR]

The lysin motif (LysM) family comprise a number of defense proteins that play important roles in plant immunity. The LysM family includes LysM-containing receptor-like proteins (LYP) and LysM-containing receptor-like kinase (LYK). LysM generally recognizes the chitin and peptidoglycan derived from bacteria and fungi. Approximately 4000 proteins with the lysin motif (Pfam PF01476) are found in prokaryotes and eukaryotes. Our study identified 57 LysM genes and 60 LysM proteins in wheat and renamed these genes and proteins based on chromosome distribution. According to the phylogenetic and gene structure of intron–exon distribution analysis, the 60 LysM proteins were classified into seven groups. Gene duplication events had occurred among the LysM family members during the evolution process, resulting in an increase in the LysM gene family. Synteny analysis suggested the characteristics of evolution of the LysM family in wheat and other species. Systematic analysis of these species provided a foundation of LysM genes in crop defense. A comprehensive analysis of the expression and cis-elements of LysM gene family members suggested that they play an essential role in defending against plant pathogens. The present study provides an overview of the LysM family in the wheat genome as well as information on systematic, phylogenetic, gene duplication, and intron–exon distribution analyses that will be helpful for future functional analysis of this important protein family, especially in Gramineae species. [ABSTRACT FROM AUTHOR]

Identifying disease-associated microRNAs (disease miRNAs) contributes to the understanding of disease pathogenesis. Most previous computational biology studies focused on multiple kinds of connecting edges of miRNAs and diseases, including miRNA–miRNA similarities, disease–disease similarities, and miRNA–disease associations. Few methods exploited the node attribute information related to miRNA family and cluster. The previous methods do not completely consider the sparsity of node attributes. Additionally, it is challenging to deeply integrate the node attributes of miRNAs and the similarities and associations related to miRNAs and diseases. In the present study, we propose a novel method, known as MDAPred, based on nonnegative matrix factorization to predict candidate disease miRNAs. MDAPred integrates the node attributes of miRNAs and the related similarities and associations of miRNAs and diseases. Since a miRNA is typically subordinate to a family or a cluster, the node attributes of miRNAs are sparse. Similarly, the data for miRNA and disease similarities are sparse. Projecting the miRNA and disease similarities and miRNA node attributes into a common low-dimensional space contributes to estimating miRNA-disease associations. Simultaneously, the possibility that a miRNA is associated with a disease depends on the miRNA's neighbour information. Therefore, MDAPred deeply integrates projections of multiple kinds of connecting edges, projections of miRNAs node attributes, and neighbour information of miRNAs. The cross-validation results showed that MDAPred achieved superior performance compared to other state-of-the-art methods for predicting disease-miRNA associations. MDAPred can also retrieve more actual miRNA-disease associations at the top of prediction results, which is very important for biologists. Additionally, case studies of breast, lung, and pancreatic cancers further confirmed the ability of MDAPred to discover potential miRNA–disease associations. [ABSTRACT FROM AUTHOR]

Predicting novel uses for drugs using their chemical, pharmacological, and indication information contributes to minimizing costs and development periods. Most previous prediction methods focused on integrating the similarity and association information of drugs and diseases. However, they tended to construct shallow prediction models to predict drug-associated diseases, which make deeply integrating the information difficult. Further, path information between drugs and diseases is important auxiliary information for association prediction, while it is not deeply integrated. We present a deep learning-based method, CGARDP, for predicting drug-related candidate disease indications. CGARDP establishes a feature matrix by exploiting a variety of biological premises related to drugs and diseases. A novel model based on convolutional neural network (CNN) and gated recurrent unit (GRU) is constructed to learn the local and path representations for a drug-disease pair. The CNN-based framework on the left of the model learns the local representation of the drug-disease pair from their feature matrix. As the different paths have discriminative contributions to the drug-disease association prediction, we construct an attention mechanism at the path level to learn the informative paths. In the right part, a GRU-based framework learns the path representation based on path information between the drug and the disease. Cross-validation results indicate that CGARDP performs better than several state-of-the-art methods. Further, CGARDP retrieves more real drug-disease associations in the top part of the prediction result that are of concern to biologists. Case studies on five drugs demonstrate that CGARDP can discover potential drug-related disease indications. [ABSTRACT FROM AUTHOR]

Molecular computing and bioinformatics are two important interdisciplinary sciences that study molecules and computers. Molecular computing is a branch of computing that uses DNA, biochemistry, and molecular biology hardware, instead of traditional silicon-based computer technologies. Research and development in this area concerns theory, experiments, and applications of molecular computing. The core advantage of molecular computing is its potential to pack vastly more circuitry onto a microchip than silicon will ever be capable of—and to do it cheaply. Molecules are only a few nanometers in size, making it possible to manufacture chips that contain billions—even trillions—of switches and components. To develop molecular computers, computer scientists must draw on expertise in subjects not usually associated with their field, including organic chemistry, molecular biology, bioengineering, and smart materials. Bioinformatics works on the contrary; bioinformatics researchers develop novel algorithms or software tools for computing or predicting the molecular structure or function. Molecular computing and bioinformatics pay attention to the same object, and have close relationships, but work toward different orientations. [ABSTRACT FROM AUTHOR]

A reaction system is a modeling framework for investigating the functioning of the living cell, focused on capturing cause–effect relationships in biochemical environments. Biochemical processes in this framework are seen to interact with each other by producing the ingredients enabling and/or inhibiting other reactions. They can also be influenced by the environment seen as a systematic driver of the processes through the ingredients brought into the cellular environment. In this paper, the first attempt is made to implement reaction systems in the hardware. We first show a tight relation between reaction systems and synchronous digital circuits, generally used for digital electronics design. We describe the algorithms allowing us to translate one model to the other one, while keeping the same behavior and similar size. We also develop a compiler translating a reaction systems description into hardware circuit description using field-programming gate arrays (FPGA) technology, leading to high performance, hardware-based simulations of reaction systems. This work also opens a novel interesting perspective of analyzing the behavior of biological systems using established industrial tools from electronic circuits design. [ABSTRACT FROM AUTHOR]

The human KRAS (Kirsten rat sarcoma) is an oncogene, involved in the regulation of cell growth and division. The mutations in the KRAS gene have the potential to cause normal cells to become cancerous in human lungs. In the present study, we focus on non-synonymous single nucleotide polymorphisms (nsSNPs), which are point mutations in the DNA sequence leading to the amino acid variants in the encoded protein. To begin with, we developed a pipeline to utilize a set of computational tools in order to obtain the most deleterious nsSNPs (Q22K, Q61P, and Q61R) associated with lung cancer in the human KRAS gene. Furthermore, molecular dynamics simulation and structural analyses of the 3D structures of native and mutant proteins confirmed the impact of these nsSNPs on the stability of the protein. Finally, the experimental results demonstrated that the structural stability of the mutant proteins was worse than that of the native protein. This study provides significant guidance for narrowing down the number of KRAS mutations to be screened as potential diagnostic biomarkers and to better understand the structural and functional mechanisms of the KRAS protein. [ABSTRACT FROM AUTHOR]

Xyloglucan endotransglucosylase/hydrolases (XTHs)—a family of xyloglucan modifying enzymes—play an essential role in the construction and restructuring of xyloglucan cross-links. However, no comprehensive study has been performed on this gene family in barley. A total of 24 HvXTH genes (named HvXTH1-24) and an EG16 member were identified using the recently completed genomic database of barley (Hordeum vulgare). Phylogenetic analysis showed that 24 HvXTH genes could be classified into three phylogenetic groups: (I/II, III-A and III-B) and HvXTH15 was in the ancestral group. All HvXTH protein members—except HvXTH15—had a conserved N-glycosylation site. The genomic location of HvXTHs on barley chromosomes showed that the 24 genes are unevenly distributed on the 7 chromosomes, with 10 of them specifically located on chromosome 7H. A structure-based sequence alignment demonstrates that each XTH possesses a highly conserved domain (ExDxE) responsible for catalytic activity. Expression profiles based on the barley genome database showed that HvXTH family members display different expression patterns in different tissues and at different stages. This study is the first systematic genomic analysis of the barley HvXTH gene family. Our results provide valuable information that will help to elucidate the roles of HvXTH genes in the growth and development of barley. [ABSTRACT FROM AUTHOR]

Recent research in DNA nanotechnology has demonstrated that biological substrates can be used for computing at a molecular level. However, in vitro demonstrations of DNA computations use preprogrammed, rule-based methods which lack the adaptability that may be essential in developing molecular systems that function in dynamic environments. Here, we introduce an in vitro molecular algorithm that 'learns' molecular models from training data, opening the possibility of 'machine learning' in wet molecular systems. Our algorithm enables enzymatic weight update by targeting internal loop structures in DNA and ensemble learning, based on the hypernetwork model. This novel approach allows massively parallel processing of DNA with enzymes for specific structural selection for learning in an iterative manner. We also introduce an intuitive method of DNA data construction to dramatically reduce the number of unique DNA sequences needed to cover the large search space of feature sets. By combining molecular computing and machine learning the proposed algorithm makes a step closer to developing molecular computing technologies for future access to more intelligent molecular systems. [ABSTRACT FROM AUTHOR]

The prediction of protein subcellular localization is critical for inferring protein functions, gene regulations and protein-protein interactions. With the advances of high-throughput sequencing technologies and proteomic methods, the protein sequences of numerous yeasts have become publicly available, which enables us to computationally predict yeast protein subcellular localization. However, widely-used protein sequence representation techniques, such as amino acid composition and the Chou's pseudo amino acid composition (PseAAC), are difficult in extracting adequate information about the interactions between residues and position distribution of each residue. Therefore, it is still urgent to develop novel sequence representations. In this study, we have presented two novel protein sequence representation techniques including Generalized Chaos Game Representation (GCGR) based on the frequency and distributions of the residues in the protein primary sequence, and novel statistics and information theory (NSI) reflecting local position information of the sequence. In the GCGR + NSI representation, a protein primary sequence is simply represented by a 5-dimensional feature vector, while other popular methods like PseAAC and dipeptide adopt features of more than hundreds of dimensions. In practice, the feature representation is highly efficient in predicting protein subcellular localization. Even without using machine learning-based classifiers, a simple model based on the feature vector can achieve prediction accuracies of 0.8825 and 0.7736 respectively for the CL317 and ZW225 datasets. To further evaluate the effectiveness of the proposed encoding schemes, we introduce a multi-view features-based method to combine the two above-mentioned features with other well-known features including PseAAC and dipeptide composition, and use support vector machine as the classifier to predict protein subcellular localization. This novel model achieves prediction accuracies of 0.927 and 0.871 respectively for the CL317 and ZW225 datasets, better than other existing methods in the jackknife tests. The results suggest that the GCGR and NSI features are useful complements to popular protein sequence representations in predicting yeast protein subcellular localization. Finally, we validate a few newly predicted protein subcellular localizations by evidences from some published articles in authority journals and books. [ABSTRACT FROM AUTHOR]

Patients with uncontrolled diabetes are susceptible to implant failure due to impaired bone metabolism. Hypoxia-inducible factor 1α (HIF-1α), a transcription factor that is up-regulated in response to reduced oxygen during bone repair, is known to mediate angiogenesis and osteogenesis. However, its function is inhibited under hyperglycemic conditions in diabetic patients. This study thus evaluates the effects of exogenous HIF-1α on bone formation around implants by applying HIF-1α to diabetic mice and normal mice via a protein transduction domain (PTD)-mediated DNA delivery system. Implants were placed in the both femurs of diabetic and normal mice. HIF-1α and placebo gels were injected to implant sites of the right and left femurs, respectively. We found that bone-to-implant contact (BIC) and bone volume (BV) were significantly greater in the HIF-1α treated group than placebo in diabetic mice (p < 0.05). Bioinformatic analysis showed that diabetic mice had 216 differentially expressed genes (DEGs) and 21 target genes. Among the target genes, NOS2, GPNMB, CCL2, CCL5, CXCL16, and TRIM63 were found to be associated with bone formation. Based on these results, we conclude that local administration of HIF-1α via PTD may boost bone formation around the implant and induce gene expression more favorable to bone formation in diabetic mice. [ABSTRACT FROM AUTHOR]

Whereas the concept of intrinsic disorder derives from biophysical observations of the lack of structure of proteins or protein regions under native conditions, many of our respective concepts rest on proteome-scale bioinformatics predictions. It is established that most predictors work reliably on proteins commonly encountered, but it is often neglected that we know very little about their performance on proteins of microorganisms that thrive in environments of extreme temperature, pH, or salt concentration, which may cause adaptive sequence composition bias. To address this issue, we predicted structural disorder for the complete proteomes of different extremophile groups by popular prediction methods and compared them to those of the reference mesophilic group. While significant deviations from mesophiles could be explained by a lack or gain of disordered regions in hyperthermophiles and radiotolerants, respectively, we found systematic overprediction in the case of halophiles. Additionally, examples were collected from the Protein Data Bank (PDB) to demonstrate misprediction and to help understand the underlying biophysical principles, i.e., halophilic proteins maintain a highly acidic and hydrophilic surface to avoid aggregation in high salt conditions. Although sparseness of data on disordered proteins from extremophiles precludes the development of dedicated general predictors, we do formulate recommendations for how to address their disorder with current bioinformatics tools. [ABSTRACT FROM AUTHOR]

As an abundant post-transcriptional modification, dihydrouridine (D) has been found in transfer RNA (tRNA) from bacteria, eukaryotes, and archaea. Nonetheless, knowledge of the exact biochemical roles of dihydrouridine in mediating tRNA function is still limited. Accurate identification of the position of D sites is essential for understanding their functions. Therefore, it is desirable to develop novel methods to identify D sites. In this study, an ensemble classifier was proposed for the detection of D modification sites in the Saccharomyces cerevisiae transcriptome by using heterogeneous features. The jackknife test results demonstrate that the proposed predictor is promising for the identification of D modification sites. It is anticipated that the proposed method can be widely used for identifying D modification sites in tRNA. [ABSTRACT FROM AUTHOR]

Accumulating evidence progressively indicated that microRNAs (miRNAs) play a significant role in the pathogenesis of diseases through many experimental studies; therefore, developing powerful computational models to identify potential human miRNA–disease associations is vital for an understanding of the disease etiology and pathogenesis. In this paper, a weighted interactive network was firstly constructed by combining known miRNA–disease associations, as well as the integrated similarity between diseases and the integrated similarity between miRNAs. Then, a new computational method implementing the newly weighted interactive network was developed for discovering potential miRNA–disease associations (WINMDA) by integrating the T most similar neighbors and the shortest path algorithm. Simulation results show that WINMDA can achieve reliable area under the receiver operating characteristics (ROC) curve (AUC) results of 0.9183 ± 0.0007 in 5-fold cross-validation, 0.9200 ± 0.0004 in 10-fold cross-validation, 0.9243 in global leave-one-out cross-validation (LOOCV), and 0.8856 in local LOOCV. Furthermore, case studies of colon neoplasms, gastric neoplasms, and prostate neoplasms based on the Human microRNA Disease Database (HMDD) database were implemented, for which 94% (colon neoplasms), 96% (gastric neoplasms), and 96% (prostate neoplasms) of the top 50 predicting miRNAs were confirmed by recent experimental reports, which also demonstrates that WINMDA can effectively uncover potential miRNA–disease associations. [ABSTRACT FROM AUTHOR]

Residues in proteins that are in close spatial proximity are more prone to covariate as their interactions are likely to be preserved due to structural and evolutionary constraints. If we can detect and quantify such covariation, physical contacts may then be predicted in the structure of a protein solely from the sequences that decorate it. To carry out such predictions, and following the work of others, we have implemented a multivariate Gaussian model to analyze correlation in multiple sequence alignments. We have explored and tested several numerical encodings of amino acids within this model. We have shown that 1D encodings based on amino acid biochemical and biophysical properties, as well as higher dimensional encodings computed from the principal components of experimentally derived mutation/substitution matrices, do not perform as well as a simple twenty dimensional encoding with each amino acid represented with a vector of one along its own dimension and zero elsewhere. The optimum obtained from representations based on substitution matrices is reached by using 10 to 12 principal components; the corresponding performance is less than the performance obtained with the 20-dimensional binary encoding. We highlight also the importance of the prior when constructing the multivariate Gaussian model of a multiple sequence alignment. [ABSTRACT FROM AUTHOR]

The interaction of death-associated protein kinase 1 (DAPK1) with the 2B subunit (GluN2B) C-terminus of N-methyl-D-aspartate receptor (NMDAR) plays a critical role in the pathophysiology of depression and is considered a potential target for the structure-based discovery of new antidepressants. However, the 3D structures of C-terminus residues 1290–1310 of GluN2B (GluN2B-CT1290-1310) remain elusive and the interaction between GluN2B-CT1290-1310 and DAPK1 is unknown. In this study, the mechanism of interaction between DAPK1 and GluN2B-CT1290-1310 was predicted by computational simulation methods including protein–peptide docking and molecular dynamics (MD) simulation. Based on the equilibrated MD trajectory, the total binding free energy between GluN2B-CT1290-1310 and DAPK1 was computed by the mechanics generalized born surface area (MM/GBSA) approach. The simulation results showed that hydrophobic, van der Waals, and electrostatic interactions are responsible for the binding of GluN2B-CT1290–1310/DAPK1. Moreover, through per-residue free energy decomposition and in silico alanine scanning analysis, hotspot residues between GluN2B-CT1290-1310 and DAPK1 interface were identified. In conclusion, this work predicted the binding mode and quantitatively characterized the protein–peptide interface, which will aid in the discovery of novel drugs targeting the GluN2B-CT1290-1310 and DAPK1 interface. [ABSTRACT FROM AUTHOR]

Hot spots are the subset of interface residues that account for most of the binding free energy, and they play essential roles in the stability of protein binding. Effectively identifying which specific interface residues of protein–protein complexes form the hot spots is critical for understanding the principles of protein interactions, and it has broad application prospects in protein design and drug development. Experimental methods like alanine scanning mutagenesis are labor-intensive and time-consuming. At present, the experimentally measured hot spots are very limited. Hence, the use of computational approaches to predicting hot spots is becoming increasingly important. Here, we describe the basic concepts and recent advances of machine learning applications in inferring the protein–protein interaction hot spots, and assess the performance of widely used features, machine learning algorithms, and existing state-of-the-art approaches. We also discuss the challenges and future directions in the prediction of hot spots. [ABSTRACT FROM AUTHOR]

High-throughput technology has generated large-scale protein interaction data, which is crucial in our understanding of biological organisms. Many complex identification algorithms have been developed to determine protein complexes. However, these methods are only suitable for dense protein interaction networks, because their capabilities decrease rapidly when applied to sparse protein–protein interaction (PPI) networks. In this study, based on penalized matrix decomposition (PMD), a novel method of penalized matrix decomposition for the identification of protein complexes (i.e., PMDpc) was developed to detect protein complexes in the human protein interaction network. This method mainly consists of three steps. First, the adjacent matrix of the protein interaction network is normalized. Second, the normalized matrix is decomposed into three factor matrices. The PMDpc method can detect protein complexes in sparse PPI networks by imposing appropriate constraints on factor matrices. Finally, the results of our method are compared with those of other methods in human PPI network. Experimental results show that our method can not only outperform classical algorithms, such as CFinder, ClusterONE, RRW, HC-PIN, and PCE-FR, but can also achieve an ideal overall performance in terms of a composite score consisting of F-measure, accuracy (ACC), and the maximum matching ratio (MMR). [ABSTRACT FROM AUTHOR]

Cancer was initially considered a genetic disease. However, recent studies have revealed the connection between bacterial infections and growth of different types of cancer. The enteroinvasive strain of Mycoplasma hominis alters the normal behavior of host cells that may result in the growth of prostate cancer. The role of M. hominis in the growth and development of prostate cancer still remains unclear. The infection may regulate several factors that influence prostate cancer growth in susceptible individuals. The aim of this study was to predict M. hominis proteins targeted into the endoplasmic reticulum (ER) of the host cell, and their potential role in the induction of prostate cancer. From the whole proteome of M. hominis, 19 proteins were predicted to be targeted into the ER of host cells. The results of our study predict that several proteins of M. hominis may be targeted to the host cell ER, and possibly alter the normal pattern of protein folding. These predicted proteins can modify the normal function of the host cell. Thus, the intercellular infection of M. hominis in host cells may serve as a potential factor in prostate cancer etiology. [ABSTRACT FROM AUTHOR]