bluuebunny/crossref_metadata_2025 huggingface dataset:
QoS provisioning in WDM ring networks with tunable transceivers
Authors: Turuk Ashok K. , Kumar Rajeev
Published: January 2025

In this paper, we propose two algorithms and a node architecture to access the shared medium and to support priority based quality-of-service (QoS) in WDM ring networks. The algorithms give priority to a node having high priority request in reserving a destination node and/or a data-channel. The first algorithm selects a data-channel based on earliest availability of the data-channel, and the second with minimum scheduling latency. Both the schemes employ reservation mechanism, however, they differ from the traditional reservation mechanism in that no explicit release of the reserved resources take place. The proposed schemes are contention-free, easy to implement and require no buffers at nodes. The proposed node architecture is configured around tunable transceiver(s) and thus makes the scheme scalable. We study performance of both the schemes, by simulation, for bursty traffic modeled using an M/Pareto distribution, and compare the performance with another token based algorithm. We found that our schemes perform better in terms of wavelength utilization. However, delays are higher due to the single tunable transceiver used in our scheme as opposed to an array of transmitters and receivers in the previous work.
Anomaly intrusion detection in wireless sensor networks
Authors: Bhuse Vijay , Gupta Ajay
Published: January 2025

We propose lightweight methods to detect anomaly intrusions in wireless sensor networks (WSNs). The main idea is to reuse the already available system information that is generated at various layers of a network stack. To the best of our knowledge, this is the first such approach for anomaly intrusion detection in WSNs.
Key management and delayed verification for Ad hoc networks
Authors: Zapata Manel Guerrero
Published: January 2025

This paper proposes a key management scheme for MANET (Mobile Ad hoc NETworks) networks that uses asymmetric cryptography without requiring nodes to know the public keys of the other nodes and without requiring any kind of central server or certification authority. In addition, the paper presents a new method (“delayed verification”) to reduce the delays in route establishment for distance vector routing protocols in cases where routing messages are signed and need to be verified. It applies both solutions to a MANET distance vector routing protocol: SAODV (Secure AODV), which is an extension of AODV (Ad hoc On-demand Distance Vector routing protocol) that can be used to protect the route discovery mechanism providing security features like integrity and authentication. Finally, the paper presents results from simulations that show how this enhanced SAODV routing protocol provides the same security that the original one with a much more reduced impact in the network performance.
Client-side access control enforcement using trusted computing and PEI models
Authors: Sandhu Ravi , Zhang Xinwen , Ranganathan Kumar , Covington Michael J.
Published: January 2025

It has been recognized for some time that software alone does not provide an adequate foundation for building a high-assurance trusted platform. The emergence of industry-standard trusted computing technologies promises a revolution in this respect by providing roots of trust upon which secure applications can be developed. These technologies offer a particularly attractive platform for security policy enforcement in general distributed systems. In this paper we propose a security framework to enforce access control policies with trusted computing, by following the recently proposed policy-enforcement-implementation (PEI) models. Our architecture is based on an abstract layer of trusted hardware which can be constructed with emerging trusted computing technologies. A trusted reference monitor (TRM) is introduced beyond the trusted hardware. By monitoring and verifying the integrity and properties of running applications in a platform using the functions of trusted computing, the TRM can enforce various policies on behalf of object owners. We further extend this platform-based architecture to support general user-based access control policies, cooperating with existing services for user identity and attributes, thus potentially supporting general access control models such as lattice-based, role-based, and usage-based access control policies.
Network security policy refinement process: Expression and analysis
Authors: Laborde Romain , Barrère François , Benzekri Abdelmalek
Published: January 2025

Today, users need to access their granted services from anywhere and at any time. Network security management must evolve to satisfy these requirements. The policy based network management approach proposes to separate the rules that govern the system from the functionalities provided by it. Nevertheless, the policy rules should be consistent, correct against the objectives and enforceable onto the devices. This problem becomes complex considering the dependencies of the rules – each rule on a device can impact another rule on another device – and each device needs specific configuration according to the technologies implemented.

This article presents a formal framework for the refinement of network security management information. It includes three abstraction levels: the network security objectives, the network security tactics and the network security devices configurations. The information models of each abstraction level are formally specified and analysed (consistency, correctness and feasibility). A WBEM implementation of the formal refinement framework proves its feasibility in management architectures.
IPsec/VPN security policy correctness and assurance
Authors: Yang Yanyan , Martel Charles U. , Fu Zhi (Judy) , Wu Shyhtsun Felix
Published: January 2025

With IPsec/VPN policies being widely deployed, how to correctly specify and configure them is critical in enforcing security requirements, especially among different administrative domains across the Internet. Under current practice, IPsec/VPN policies are specified individually by system administrators from different organizations without any formal coordination. This practice implies unintentional errors due to inconsistent IPsec/VPN policies. Furthermore, Internet routing dynamics may possibly interfere with IPsec/VPN policies such that unexpected conflicts occur due to a mismatch between the routing and IPsec/VPN layers. To deal with these problems, we formally define IPsec security requirements, policies, and their correctness criteria. Based on these definitions, we present an inter-domain architecture to automatically generate correct and efficient security policies. Our approach works when we are given a set of security requirements for a single end-to-end traffic flow. We can also deal with changes when new security requirements are added. Finally, we present simulation results which evaluate the performance of our solutions.
An autonomic approach for managing security and identity management policies in enterprises
Authors: Ganek Alan , Nadalin Anthony , Nagaratnam Nataraj , Verma Dinesh
Published: January 2025

Policy driven management of secure applications and solutions is emerging as a key concept in meeting the requirements of an on demand enterprise vision. In any enterprise, there are various people acting in specific roles who contribute to the modeling, development, deployment and management of security and authorization aspects of a business application. This paper looks at the lifecycle of policies, and proposes an approach for security and authorization that is modeled using policies and rule attached to business process and models. It describes the operational and deployment aspects for autonomic behavior of policy-driven systems. This presents a pragmatic approach to find intersection points between a platform independent modeling of security and authorization policies, and the concrete articulation of policies. This approach offers a way to leverage monitoring adherence and compliance to policies both in IT and business dashboards to manage and map the relationship between business artifacts and implementation artifacts so that business policies are reflected in implementation.
Sensor-based Pervasive Healthcare System: Design and implementation
Authors: Kung Hsu-Yang , Hsu Chi-Yu , Lin Mei-Hsien
Published: January 2025

With rapid progress in wireless sensor networks (WSN) and pervasive computing technology, development of WSN-based pervasive healthcare systems, which provide patients and healthcare professionals with a convenient and efficient e-health environment, have become one of important and popular research topics in Health Information Systems (HIS). This paper proposes a Sensor-based Pervasive Healthcare (SPH) System, which comprises the Home Healthcare End (HHE) system, E-healthcare Service Provider (ESP) and E-healthcare Control Center (ECC). At the ECC, healthcare professionals remotely monitor the physiological status of patients using the WSN-based HHE system. The ESPs provide patients and healthcare professionals of the ECC with healthcare information services. The ESP is developed based on proposed Healthcare Service Middleware (HSM), which integrates the heterogeneous computing and communication devices, and provides the flexible healthcare platform to enrich the healthcare services. Additionally, a Seamless Healthcare Information Delivery (SHID) scheme is proposed to allow healthcare professionals to access patients' with their relevant healthcare data anywhere in real-time without manual manipulations. The ultimate objective of the proposed SPH system is to effectively reduce healthcare labor and to further provide a streamlined, convenient, and low cost healthcare platform for patients and healthcare professionals.
A mobile physiological monitoring system for patient transport
Authors: Shen Jui-Chi , Shih Dong-Her , Chiang Hsiu-Sen , Lin Shih-Bin
Published: January 2025

More and more intra-hospital transport of patients is required to perform special examination or therapy in recent years. The key point of all critical care transport is the continuous monitoring of vital signs. Also, with the growing popularity of wireless technology in the health care area, there is a pressing need to have a proper system in place for patient identification. Errors in patient identification and hence improper administrator of medication can lead to disastrous results. This paper proposes a mobile physiological patient monitoring system, which integrates current mobile smart phone, wireless sensor network, Bluetooth, and RFID patient identification systems for patient monitoring. This system enables continuous monitoring and patient identification during intra-hospital or inter-hospital patient transport.
Performance analysis of Modified Deficit Round Robin schedulers
Authors: Lenzini Luciano , Mingozzi Enzo , Stea Giovanni
Published: January 2025

Deficit Round Robin (DRR) is a scheduling algorithm which provides fair queuing at O(1) complexity. However, due to its round robin structure, its latency properties are not adequate for latency-critical applications, such as voice. For this reason, router manufacturers implement variants of the DRR algorithm which guarantee lower latencies to one (or a subset of) queue(s). In this paper we evaluate the performance of two such variants, both of which are known as Modified Deficit Round Robin, currently implemented in commercial routers. The comparison is carried out analytically, by deriving the latency and bandwidth guarantees of both algorithms, and by simulation.
Max–min fairness in WDM optical burst switching networks
Authors: Liu Yong , Chua Kee Chaing , Mohan Gurusamy
Published: January 2025

In this paper, we define the max–min fairness criteria for OBS networks and propose some effective schemes to provide max–min fairness to support service protection and isolation in such networks. We present extensive simulation results to show the effectiveness of the proposed schemes to achieve max–min fairness with good isolation among connections.
Analysis of the burst loss rate in OBS rings with depth limited optical buffers
Authors: Xu Huadong , Fan Ge
Published: January 2025

Optical Burst Switching (OBS) is considered as the promised solution for next generation backbone networks, but the high burst loss rate caused by the burst contention is a great hindrance to the practical use.

The authors proposed a new way to solve the burst contentions in OBS rings. As illustrated in the paper, basing the optical buffers with depth about the maximum Data Burst (DB) size and a proper wavelengths selection strategy for the local DBs the burst loss rate in an OBS ring can be decreased to a negligible level. So buffer insertion, the most successful method for asynchronous packet switching, can be adopted in OBS ring by an acceptable cost.
Homology Model Building of Hho1p Supports its Role as a Yeast Histone H1 Protein
Authors: Baxevanis Andreas D. , Landsman David
Published: January 2025

Biochemical studies to date have not been able to identify the linker histone H1 protein in the budding yeast Saccharomyces cerevisiae. Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain. To determine whether Hho1p can assume the shape of an H1 protein, homology model building experiments were performed using the structure of chicken histone H5 globular domain as the basis for comparison. A statistically significant match between each of the two globular domains of Hho1p and the chicken histone H5 structure was obtained, and probability values indicate that there is a less than 1 in 100 chance that such a match would be the result of a random event. These findings support the proposal that Hho1p acts as an "H1 dimer" and could be responsible for the decreased linker DNA length observed between nucleosomal core particles.
SEView: A Java Applet for Browsing Molecular Sequence Data
Authors: Junier Thomas , Bucher Philipp
Published: January 2025

SEView is a Java applet that represents known or predicted elements of a protein or nucleotide sequence. It replaces or supplements the textual format of databases or program output with an interactive, graphical representation that is easily available through a WWW browser. Independence from the source data's format is achieved through a description language and ad hoc translators, which make the system versatile and flexible
Muscle Actin Genes
Authors: Frech Kornelie , Quandt Kerstin , Werner Thomas
Published: January 2025

Tissue-specific gene expression is governed by enhancer and promoter sequences determining the specificity most probably by their internal organization of transcription factor binding sites. In case of muscle-specific gene expression excellent compilations of sequence regions responsible for the tissue-specificity are available. We took advantage of such a compilation in order to elucidate organizational features that are directly correlated with promoter specificity. We chose a systematic approach solely based on a sequence collection known to consist of specific regulatory regions which can in principle be applied to every precompiled set of such sequences. We were able to show that these sequences contained a detectable subgroup (actin promoters) for which it was possible to construct a highly specific promoter model recognizing the majority of all known actin sequences. The model was robust with respect to different training sets, almost 100% specific and sensitive enough to be suitable for database searches. We believe this pilot study demonstrates the general applicability of our approach as well as the concept of modular promoter organization.
Use of Contiguity on the Chromosome to Predict Functional Coupling
Authors: Overbeek Ross , Fonstein Michael , D'Souza Mark , Pusch Gordon D. , Maltsev Natalia
Published: January 2025

The availability of a growing number of completely sequenced genomes opens new opportunities for understanding of complex biological systems. Success of genome-based biology will, to a large extent, depend on the development of new approaches and tools for efficient comparative analysis of the genomes and their organization. We have developed a technique for detecting possible functional coupling between genes based on detection of potential operons. The approach involves computation of "pairs of close bidirectional best hits", which are pairs of genes that apparently occur within operons in multiple genomes. Using these pairs, one can compose evidence (based on the number of distinct genomes and the phylogenetic distance between the orthologous pairs) that a pair of genes is potentially functionally coupled. The technique has revealed a surprisingly rich and apparently accurate set of functionally coupled genes. The approach depends on the use of a relatively large number of genomes, and the amount of detected coupling grows dramatically as the number of genomes increases.
A Neural Network Model Approach to the Study of Human TAP Transporter
Authors: Brusic Vladimir , van Endert Peter , Zeleznikow John , Daniel Soizic , Hammer Jürgen , Petrovsky Nikolai
Published: January 2025

We used an artificial neural network (ANN) computer model to study peptide binding to the human transporter associated with antigen processing (TAP). After validation, an ANN model of TAP-peptide binding was used to mine a database of HLA-binding peptides to elucidate patterns of TAP binding. The affinity of HLA-binding peptides for TAP was found to differ according to the HLA supertype concerned: HLA-B27, -A3 or -A24 binding peptides had high, whereas HLA-A2, -B7 or -B8 binding peptides had low affinity for TAP. These results support the idea that TAP and particular HLA molecules may have co-evolved for efficient peptide processing and presentation. The strong similarity between the sets of peptides bound by TAP or HLA-B27 suggests functional co-evolution whereas the lack of a relationship between the sets of peptides bound by TAP or HLA-A2 is against these particular molecules having co-evolved. In support of these conclusions, the affinities of HLA-A2 and HLA-B7 binding peptides for TAP show similar distributions to that of randomly generated peptides. On the basis of these results we propose that HLA alleles constitute two separate classes: those that are TAP-efficient for peptide loading (HLA-B27, -A3 and -A24) and those that are TAP-inefficient (HLA-A2, -B7 and -B8). Computer modelling can be used to complement laboratory experiments and thereby speed up knowledge discovery in biology. In particular, we provide evidence that large-scale experiments can be avoided by combining initial experimental data with limited laboratory experiments sufficient to develop and validate appropriate computer models. These models can then be used to perform large-scale simulated experiments the results of which can then be validated by further small-scale laboratory experiments
The Death Factors: A Combinatorial Analysis
Authors: Bergeron Anne , Geanta Paul , Bergeron Dominique
Published: January 2025

This paper presents theoretical and computational tools to understand how a small group of proteins, the death factors, are involved in widely different behavior of the cell. Experiments were done using a virtual laboratory that can simulate cellular response to different external stimuli. WARNING: It is not certain which of the theoretical protein clusters described here really occur in nature. In addition, the rules of cluster assembly are combinatorial, and thus an oversimplification to describe the real situation.
CoPreTHi: A Web Tool which Combines Transmembrane Protein	Segment Prediction Methods
Authors: Promponas V.J. , Palaios G.A. , Pasquier C.M. , Hamodrakas J.S. , Hamodrakas S.J.
Published: January 2025

CoPreTHi is a Java based web application, which combines the results of methods that predict the location of transmembane segments in protein sequences into a joint prediction histogram. Clearly, the joint prediction algorithm, produces superior quality results than individual prediction schemes. The program is available at http://o2.db.uoa.gr/CoPreTHi.
Comparison of Protein Structures Reveals Monophyletic Origin of	the AdoMet-Dependent Methyltransferase Family and Mechanistic Convergence	Rather than Recent Differentiation of N4-Cytosine and N6-Adenine DNA	Methylation
Authors: Bujnicki Janusz M.
Published: January 2025

Phylogenetic analysis of the S-adenosyl-L-methionine-dependent methyltransferases was performed based on similarity of positions of main chain á-carbon atoms in published structures of members of this superfamily.  The evolutionary tree was inferred and the problem of mono/polyphyletic origin of DNA methyltransferases from the Rossmann-fold enzymes was solved, bridging two seemingly antithetical hypotheses.  The comparison of protein structures provides evidence for an evolutionary link between widely diverged subfamilies of RNA and DNA N6-adenine methyltransferases and argues against the close homology of N6-adenine and N4-cytosine methyltransferases, apparent from biochemical data and comparison of fragments of sequences.  Such evolutionary analysis of methyltransferases has never been published yet in the literature and will guide further phylogenetical studies based on both sequence and structure comparison.
Curved DNA in Promoter Sequences
Authors: Gabrielian Andrei E. , Landsman David , Bolshoy Alexander
Published: January 2025

Sequence-dependent DNA curvature is known to play an important role in initiation of transcription of many genes.  We compared the distribution of predicted intrinsic curvature of Escherichia coli and human promoter sequences with the distribution of curvature of randomly selected coding and non-coding fragments from these organisms.  Different methods of curvature calculation were found to yield mostly similar overall tendencies of DNA curvature in all groups of sequences.  According to all methods of calculation, E. coli promoters were found to be more curved than coding sequences from the same genome and random sequences with the same nucleotide composition.  By contrast, the average curvature of human promoter sequences was only marginally greater than the average curvature of human coding sequences.  Non-coding intron sequences were found to be the most curved of the human sequences examined.  Based on these observations, we hypothesize about the role of DNA curvature in promoter sequences.
secureBLAST
Authors: Wiezer Arnim , Merkl Rainer
Published: January 2025

secureBLAST supplements NCBI wwwblast with features necessary to control in an easy manageable way usage of BLAST data sets and their update. The concept we implemented allows to offer on a single BLAST server several data sets with individually configurable access rights. Security is provided by user authentication and encryption of the http traffic via SSL. By using secureBLAST, the administration of users and databases can be done via a web interface. Therefore, secureBLAST is valuable for institutions that have to restrict access to their datasets or just want to administer BLAST servers via a web interface.
Prediction of Polypeptide Fragments Exposed to the Solvent
Authors: Carugo Oliviero
Published: January 2025

A method is presented to predict those polypeptide segments within a globular protein that are more likely to be exposed to the solvent. The protein amino acidic sequence is the only information needed by this new algorithm. It uses a consensus hydrophobicity scale, derived from 28 known scales, and it is based on the comparison between the average hydrophobicity of a polypeptide fragment and the average hydrophobicity expected for a segment containing the same number of residues. The latter values are pre-computed from a non-redundant set of single chain protein structural domains. The comparison between the two average values results in a t value that readily provides the prediction with a statistical significance. A jack-knife validation analysis indicates that the protein segment predicted to be the most solvent exposed is actually solvent exposed and amongst the fragments that are most exposed. The source of a stand-alone program, written in C language, that allows the prediction of the most likely solvent exposed segment in a globular protein is available from the author.
YACOP: Enhanced Gene Prediction Obtained by a Combination of	Existing Methods
Authors: Tech Maike , Merkl Rainer
Published: January 2025

The performance of gene-predicting tools varies considerably if evaluated with respect to the parameters sensitivity and specificity or their capability to identify the correct start codon. We were interested to validate tools for gene prediction and to implement a metatool named YACOP, which combines existing tools and has a higher performance. YACOP parses and combines the output of the three gene-predicting systems Criticia, Glimmer and ZCURVE. It outperforms each of the programs tested with its high sensitivity and specificity values combined with a larger number of correctly predicted gene starts. Performance of YACOP and the gene-finding programs was tested by comparing their output with a carefully selected set of annotated genomes. We found that the problem of identifying genes in prokaryotic genomes by means of computational analysis was solved satisfactorily. In contrast, the correct localization of the start codon still appeared to be a problem, as in all cases under test at least 7.5% and up to 32.3% of the positions given in the annotations differed from the locus predicted by any of the programs tested. YACOP can be downloaded from http://www.g2l.bio.uni-goettingen.de.
Investigation of Interaction between Pax-5 Isoforms and	Thioredoxin Using De Novo Modelling Methods
Authors: Cuperlovic-Culf Miroslava , Robichaud Gilles A. , Nardini Michel , Ouellette Rodney J.
Published: January 2025

The Pax-5 transcription factor plays a crucial role in B-cell development, activation and differentiation. In murine B-cells four different isoforms of Pax-5 have been identified, and their role in the regulation of the activity of the wild-type protein was revealed although still not fully understood. Using theoretical methods, we investigated the properties of one region of the Pax-5e and Pax-5d isoforms (named UDE domain) and we present a possible theoretical model for the interaction of this domain with thioredoxin that have been previously postulated based on the experimental results. Domain UDE (MW 4.8kDa) is characterised by an extremely high ratio of positively charged residues (8) in comparisons to negatively charged amino acids (3), as well as unusually large concentrations of prolines (11.6%) and cysteines (4.7%). This is indicative of its role in protein-protein interaction. The experimental 3D structure for either UDE domain or for any analogous sequence is not yet available, and therefore we resorted to various bioinformatics methods in order to predict the secondary and 3D structure from the primary sequence of UDE. Physicochemical properties of the predicted UDE structure gave more indication about possibilities for UDE-thioredoxin binding. In addition, UDE domain was shown to have both sequence and structure analogous to a segment of NAD-reducing hydrogenase HOXS α subunit which is believed to interact with thioredoxin. These studies showed that the UDE domain in Pax-5d and Pax-5e represents an ideal binding site for thioredoxin and we developed a model of UDE-TRX complex with two disulphide bridges. The active site of thioredoxin remained exposed after binding to UDE in this model and therefore binding of thioredoxin to Pax-5d could explain the unexpectedly high resistance of this isoform to oxidation. The complex between thioredoxin and Pax-5e can be a method for transportation of thioredoxin into the nucleus and also into the the vicinity of Pax-5a, explaining the observed activator role of Pax-5e.
Seven Clusters in Genomic Triplet Distributions
Authors: Gorban Alexander N. , Zinovyev Andrei Y. , Popova Tatyana G.
Published: January 2025

In several recent papers new gene-detection algorithms were proposed for detecting protein-coding regions without requiring a learning dataset of already known genes. The fact that unsupervised genedetection is possible is closely connected to the existence of a cluster structure in oligomer frequency distributions. In this paper we study the cluster structure of several genomes in the space of their triplet frequencies, using a pure data exploration strategy. Several complete genomic sequences were analyzed, using the visualization of tables of triplet frequencies in a sliding window. The distribution of 64-dimensional vectors of triplet frequencies displays a well-detectable cluster structure. The structure was found to consist of seven clusters, corresponding to proteincoding information in three possible phases in one of the two complementary strands and in the non-coding regions with high accuracy (higher than 90% on nucleotide level). Visualizing and understanding the structure allows to analyze effectively the performance of different gene-prediction tools. Since the method does not require extraction of ORFs, it can be applied even for unassembled genomes.
waveTM: Wavelet-Based Transmembrane Segment Prediction
Authors: Pashou Evanthia E. , Litou Zoi I. , Liakopoulos Theodore D. , Hamodrakas Stavros J.
Published: January 2025

waveTM is a web tool for the prediction of transmembrane segments in α-helical membrane proteins. Prediction is performed by a dynamic programming algorithm on wavelet-denoised 'hydropathy' signals. Users submit a protein sequence and receive interactively the results. Topology prediction can also be obtained in conjunction with the algorithm OrienTM. A web server that implements the waveTM algorithm is freely available at http://bioinformatics.biol.uoa.gr/waveTM.
Rapid Detection of Conserved Regions in Protein Sequences Using	Wavelets
Authors: Krishnan Arun , Li Kuo-Bin , Issac Praveen
Published: January 2025

We present an algorithm to detect protein sub-structural motifs from primary sequence. The input to the algorithm is a set of aligned multiple protein sequences. It uses wavelet transforms to decompose protein sequences represented numerically by different indices (such as polarity, accessible surface area or electron-ion integration potentials of the amino acids). The numerical representation of a protein sequence has significant correlation with its biological activity, thus common motifs are expected to be observable from the wavelet spectrum. The decomposed signals are then up-sampled and similarity search techniques are used to identify similar regions across all the proteins at multiple scales. Results indicate that wavelet transform techniques are a promising approach for rapid motif detection.
Ideal Discrimination of Discrete Clinical Endpoints Using	Multilocus Genotypes
Authors: Hahn Lance W. , Moore Jason H.
Published: January 2025

Multifactor Dimensionality Reduction (MDR) is a method for the classification and prediction of discrete clinical endpoints using attributes constructed from multilocus genotype data. Empirical studies with both real and simulated data suggest that MDR has good power for detecting gene-gene interactions in the absence of independent main effects. The purpose of this study is to develop an objective, theory-driven approach to evaluate the strengths and limitations of MDR. To accomplish this goal, we borrow concepts from ideal observer analysis used in visual perception to evaluate the theoretical limits of classifying and predicting discrete clinical endpoints using multilocus genotype data. We conclude that MDR ideally discriminates between low risk and high risk subjects using attributes constructed from multilocus genotype data. We also show that the classification approach used once a multilocus attribute is constructed is similar to that of a naïve Bayes classifier. This study prov ides a theoretical foundation for the continued development, evaluation, and application of MDR as a data mining tool in the domain of statistical genetics and genetic epidemiology.
Classification of Short Kinetics by Shape
Authors: Sieburg Hans B. , Müller-Sieburg Christa E.
Published: January 2025

Discerning significant relationships in small data sets remains challenging. We introduce here the Hamming distance matrix and show that it is a quantitative classifier of similarities among short time-series. Its elements are derived by computing a modified form of the Hamming distance of pairs of symbol sequences obtained from the original data sets. The values from the Hamming distance matrix are then amenable to statistical analysis. Examples from stem cell research are presented to illustrate different aspects of the method. The approach is likely to have applications in many fields.
Using Amino Acid Patterns to Accurately Predict Translation	Initiation Sites
Authors: Liu Huiqing , Han Hao , Li Jinyan , Wong Limsoon
Published: January 2025

The translation initiation site (TIS) prediction problem is about how to correctly identify TIS in mRNA, cDNA, or other types of genomic sequences. High prediction accuracy can be helpful in a better understanding of protein coding from nucleotide sequences. This is an important step in genomic analysis to determine protein coding from nucleotide sequences. In this paper, we present an in silico method to predict translation initiation sites in vertebrate cDNA or mRNA sequences. This method consists of three sequential steps as follows. In the first step, candidate features are generated using k-gram amino acid patterns. In the second step, a small number of top-ranked features are selected by an entropy-based algorithm. In the third step, a classification model is built to recognize true TISs by applying support vector machines or ensembles of decision trees to the selected features. We have tested our method on several independent data sets, including two public ones and our own extracted sequences. The experimental results achieved are better than those reported previously using the same data sets. Our high accuracy not only demonstrates the feasibility of our method, but also indicates that there might be "amino acid" patterns around TIS in cDNA and mRNA sequences.
Molecular Chaperones: Proposal of a Systematic Computer-Oriented	Nomenclature and Construction of a Centralized Database
Authors: Sghaier Haïtham , Ai Thuy Le Huyen , Horiike Tokumasa , Shinozawa Takao
Published: January 2025

Molecular chaperones are a wide group of unrelated protein families whose role is to assist others proteins. Comparably, under environmental stress, stress proteins behave as biocatalysts of protein stabilization. Stress proteins include a large class of proteins that were originally termed heat shock proteins (HSPs) due to their initial discovery in tissues exposed to elevated temperatures. Many, but not all, stress proteins and HSPs are molecular chaperones. Moreover, not all HSPs are derivable from stress. HSPs are structurally diversified by the contribution of various domains having specific roles. HSPs have been grouped, mainly on the basis of their molecular masses, into specific families that include small HSPs (sHSPs)/α-crystallins, HSP10s, HSP40s, HSP60s, HSP70s, HSP90s, HSP100s and HSP110s. The names of these major families are historical artefacts with limited information content. Using the current databases, names and proteic domains of many molecular chaperones in different species were analyzed. Although traditional names of HSPs are trivial, it is unrealistic to suggest replacing them, because they are preferred and widely used. Here we suggest that these traditional names be chaperoned, in silico, by a systematic nomenclature. Thus, for example, with the same intent of use of [trioxygen: O $_3$ ] for ozone, we propose here C7HSP70[Ehsa]ER-P11021 for GRP78 (78 kDa endoplasmic Human molecular chaperone in HSP70 superfamily with P11021 as its accession number in the database of the National Center for Biotechnology Information (NCBI)). The proposed systematic computer-oriented naming and classification method is designed for HSPs and also their partners based on the number of amino acids, domain structure, phylogenetic domain, localization in the cell and accession number as stated in the NCBI. Arabidopsis thaliana was analyzed as a model, because it contains a large number of various HSPs localized in several organelles. Overall, this naming system helps in building, optimizing and managing a novel online database entirely devoted to HSPs. The purported taxonomy, coupled with the newly constructed database, can contribute to studies involving large amounts of stored data on HSPs.
Using Prior Knowledge to Improve Genetic Network Reconstruction	from Microarray Data
Authors: Le Phillip P. , Bahl Amit , Ungar Lyle H.
Published: January 2025

The use of Bayesian Network methods to recover transcriptional regulatory networks from static microarray data is an active area of bioinformatics research. However, early work in this area lacked realistic analysis of the effects of data set size on learning performance and ignored the potentially immense benefits of using prior biological knowledge. More recent work which has utilized such information has tended to focus on qualitative descriptions of the results.

In this paper, we construct a detailed, realistic model for glucose homeostasis and use this model to generate static, synthetic gene expression data. We then use a Bayesian Network method to reconstruct this genetic network from the synthetic microarray data utilizing various amounts and types of prior knowledge.

By quantitatively analyzing the effects of data set size and the incorporation of different types of prior biological knowledge on our ability to reconstruct the original network, we show that characteristic portions of genetic networks can be reconstructed from microarray data. Incorporating prior knowledge into the learning scheme greatly reduces the data required, allowing these reverse engineering techniques to be used to learn regulatory interactions from microarray data sets of realistic size.
Curvature Distribution in Prokaryotic Genomes
Authors: Kozobay-Avraham Limor , Hosid Sergey , Bolshoy Alexander
Published: January 2025

DNA curvature is known to play a biological role in gene regulation, in particular, initiation of transcription. We applied the software CURVATURE based on the wedge model to predict whether promoter regions of certain prokaryotes may be characterized by higher intrinsic DNA curvature located within or upstream to these regions. The main purpose was to verify our earlier hypothesis that the DNA curvature plays a biological role in gene regulation in mesophilic as compared to hyperthermophilic prokaryotes, i.e., DNA curvature presumably has a functional adaptive significance determined by temperature selection. Therefore, we analyzed all available complete prokaryotic genomes. The analysis showed that there is a group of genomes with a relatively high average DNA curvature upstream of start of genes. Remarkably, all organisms of this group appeared to be mesophilic, which is a full confirmation of the former hypothesis. The conservative patterns of genomic curvature distribution across different mesophilic bacterial and archaeal genomes presented in this study provide a new, convincing indication that curved DNA is evolutionarily preserved and determined by temperature selection. Moreover, we found a rather peculiar property of hyperthermophilic prokaryotes: the coding regions are predicted to be significantly more curved than it would be expected from their dinucleotide composition.
Distributions of Exons and Introns in the Human Genome
Authors: Sakharkar Meena Kishore , Chow Vincent T.K. , Kangueane Pandjassarame
Published: January 2025

The human genome is revisited using exon and intron distribution profiles. The 26,564 annotated genes in the human genome (build October, 2003) contain 233,785 exons and 207,344 introns. On average, there are 8.8 exons and 7.8 introns per gene. About 80% of the exons on each chromosome are < 200 bp in length. < 0.01% of the introns are < 20 bp in length and < 10% of introns are more than 11,000 bp in length. These results suggest constraints on the splicing machinery to splice out very long or very short introns and provide insight to optimal intron length selection. Interestingly, the total length in introns and intergenic DNA on each chromosome is significantly correlated to the determined chromosome size with a coefficient of correlation r = 0.95 and r = 0.97, respectively. These results suggest their implication in genome design.
Selecting SNPs for Association Studies Based on Population Frequencies: A Novel Interactive Tool and Its Application to Polygenic Diseases
Authors: Möller Steffen , Koczan Dirk , Serrano-Fernandez Pablo , Zettl Uwe K. , Thiesen Hans-Jürgen , Ibrahim Saleh M.
Published: January 2025

Common complex polygenic diseases as autoimmune diseases have not been completely understood on a molecular level. While many genes are known to be involved in the pathways responsible for the phenotype, explicit causes for the susceptibility of the disease remain to be elucidated. The susceptibility to disease is thought to be the result of genetic epistatic interactions between common polymorphic genes. This polymorphism is mostly caused by single nucleotide polymorphisms (SNPs). Human subpopulations are known to differ in the susceptibility to the diseases and generally in the distribution of single nucleotide polymorphisms.

The here presented approach retrieves SNPs with the most divergent frequencies for selected human subpopulations to help defining properties for the experimental verification of SNPs within defined regions. A web-accessible program implementing this approach was evaluated for multiple sclerosis (MS), a common human polygenic disease. A link to a summary of data from "The SNP Consortium" (TSC) with sex-dependencies of SNPs is available. Associations of SNPs to genes, genetic markers and chromosomal loci are retrieved from the Ensembl project. This tool is recommended to be used in conjunction with microarray analyses or marker association studies that link genes or chromosomal loci to particular diseases.
Large-Scale Collection and Characterization of Promoters of Human and Mouse Genes
Authors: Suzuki Yutaka , Yamashita Riu , Shirota Matsuyuki , Sakakibara Yuta , Chiba Joe , Mizushima-Sugano Junko , Kel Alexander E. , Arakawa Takahiro , Carninci Piero , Kawai Jun , Hayashizaki Yoshihide , Takagi Toshihisa , Nakai Kenta , Sugano Sumio
Published: January 2025

We report the generation and initial characterization of a large-scale collection of sequences of putative promoter regions (PPRs) of human and mouse genes. Based on our unique collection of 400,225 and 580,209 human and mouse full-length cDNAs, we determined exact transcriptional start sites (TSSs). Using positional information of the TSSs, we could retrieve adjacent sequences as PPRs for 8,793 and 6,875 human and mouse genes, respectively. The positions of the PPRs were 4 kb upstream to previously reported 5'-ends of cDNAs on average, demonstrating that full-length cDNA information is indispensable for this purpose. Among those PPRs supported by experimentally validated TSSs, 3,324 could be paired as mutually homologous genes between human and mouse and were used for the comprehensive comparative studies. The sequence identities in the proximal regions of the TSSs were 45% on average, and 22,794 putative transcription factor binding sites that are conserved between human and mouse were identified. The data resource created in the present work and the results of the sequences' initial characterization should lay the firm foundation for deciphering the transcriptional modulations of human genes. All the data were deposited and made available through a database for comparative studies, DBTSS.
Recognition of Remotely Related Structural Homologues Using Sequence Profiles of Aligned Homologous Protein Structures
Authors: Namboori Seema , Srinivasan Narayanaswamy , Pandit Shashi B.
Published: January 2025

In order to bridge the gap between proteins with three-dimensional (3-D) structural information and those without 3-D structures, extensive experimental and computational efforts for structure recognition are being invested. One of the rapid and simple computational approaches for structure recognition makes use of sequence profiles with sensitive profile matching procedures to identify remotely related homologous families. While adopting this approach we used profiles that are generated from structure-based sequence alignment of homologous protein domains of known structures integrated with sequence homologues. We present an assessment of this fast and simple approach. About one year ago, using this approach, we had identified structural homologues for 315 sequence families, which were not known to have any 3-D structural information. The subsequent experimental structure determination for at least one of the members in 110 of 315 sequence families allowed a retrospective assessment of the correctness of structure recognition. We demonstrate that correct folds are detected with an accuracy of 96.4% (106/110). Most (81/106) of the associations are made correctly to the specific structural family. For 23/106, the structure associations are valid at the superfamily level. Thus, profiles of protein families of known structure when used with sensitive profile-based search procedure result in structure association of high confidence. Further assignment at the level of superfamily or family would provide clues to probable functions of new proteins. Importantly, the public availability of these profiles from us could enable one to perform genome wide structure assignment in a local machine in a fast and accurate manner.
A DNA Motif Lexicon: Cataloguing and Annotating Sequences
Authors: Dyer Betsey D. , LeBlanc Mark D. , Benz Stephen , Cahalan Peter , Donorfio Brian , Sagui Patrick , Villa Adam , Williams Gregory
Published: January 2025

The rapid proliferation of genomic DNA sequences has created a significant need for software that can both focus on relatively small areas (such as within genes or promoters) and provide wide-zoom views of patterns across entire genomes. We present our DNA Motif Lexicon that enables users to perform genome-wide searches for motifs of interest and create customizable results pages, where results differ in the degree and extent of annotation. Searching for a particular motif is akin to a word search in a natural language; our motif lexicon speaks to this new time when we will increasingly rely upon DNA dictionaries that offer rich types of annotation. Indeed, the concept of "lexomics", introduced in this paper may be appropriate to the types of meta-analyses relevant to the deciphering of regulatory information. Currently supporting five genomes, our web-based lexicon allows users to look up motifs of interest and build user-defined result pages to include the following: (1) all base pair locations where a motif is found with links to further search the "neighborhoods" near each of these locations; whether each location of the motif is genic (within) a gene, intergenic, or a bridging sequence (overlapping a gene boundary) (2) NCBI hot-links to nearest upstream and downstream genes for each location (3) statistical information about the query (4) whether the motif is a certain type of repeat (5) links for the reverse, complement and reverse-complement of the motif of interest and (6) hot-links to PubMed abstracts which mention the motif of interest. A software framework facilitates the continual development of new annotation modules. The tool is located at: http://genomics.wheatoncollege.edu/cgi-bin/lexicon.exe.