bluuebunny/crossref_metadata_2025 huggingface dataset:
Considerations on the relationship between vocal performance, repertoire choices, and self confidence
Authors: Festeu Adriana
Published: January 2025

This article examines the rapport between repertoire choices and self-confidence which ultimately impacts the quality of vocal performance. This research is based on semi-structured interviews with renowned opera singers that the author undertook during her PhD studies, as well as the author’s own experience as an opera performer and voice teacher in higher education. The conclusion proposes that there is a complex interplay between vocal technique, personal identity and the performer’s sense of artistic fulfilment.
Implementation of The Clean and Healthy Living Behavior (PHBS) Fostering Program in Indramayu Regency : Case Study in The Work Area of UPTD Puskesmas Jatibarang
Authors: Ismanudin Ismanudin , Nirwana Senja
Published: January 2025

This study was conducted to determine the implementation of the household PHBS development program in the working area of UPTD Puskesmas Jatibarang. The research focused on motivating, facilitating, directing, communicating, and controlling aspects carried out by UPTD Puskesmas leaders and PHBS program managers in the UPTD Puskesmas Jatibarang working area, Indramayu Regency. In addition, identifying and analyzing the constraining factors in the implementation of the PHBS coaching program. This study used a qualitative method with a descriptive phenomenological approach. Samples were selected purposively, with key informants being the head of the UPTD Puskesmas Jatibarang and the PHBS program manager. Research informants were PHBS cadres, housewives, and community leaders.  Data collection techniques through in-depth interviews and observations of PHBS management informants at the puskesmas level, PHBS cadres, housewives, and community leaders, as well as documentation techniques. Data analysis techniques through qualitative data analysis techniques, through data reduction, data display, and conclusion drawing/verification. The results showed that the achievement of 10 indicators of PHBS in the work area of the UPTD Puskesmas Jastibarang in 2011 had reached 82.1%, while in 2012 the program achievement was seen to increase to 90.3% or an average of 86.2% per year. However, judging from the achievement of the total percentage of healthy households in 2012 only reached 36.4% or decreased compared to 2011 which had reached 56.3% of healthy households, so that the PHBS program in the family setting has not been fully effective.  There are still internal and external constraints in the management of the PHBS program, as well as the need for coordination and synergistic cooperation with cross-program, cross-sector and other related.
Illuminator: Increasing Synergies Between Medicinal And	Computational Chemists
Authors: Gobbi Alberto , Lardy Matthew , Kim Sun Hee , Ruebsam Frank , Tran Martin , Webber Stephen E. , Xiang Alan X.
Published: January 2025

We present Illuminator, a user-friendly web front end to computational models such as docking and 3D shape similarity calculations. Illuminator was specifically created to allow non-experts to design and submit molecules to computational chemistry programs. As such it provides a simple user interface allowing users to submit jobs starting from a 2D structure. The models provided are pre-optimized by computational chemists for each specific target. We provide an example of how Illuminator was used to prioritize the design of molecular substituents in the Anadys HCV Polymerase (NS5B) project. With 7500 submitted jobs in 1.5 years, Illuminator has allowed project teams at Anadys to accelerate the optimization of novel leads. It has also improved communication between project members and increased demand for computational drug discovery tools.
Sources of Systematic Error in Functional Annotation of Genomes: Domain Rearrangement, Non-Orthologous Gene Displacement and Operon Disruption
Authors: Galperin Michael Y. , Koonin Eugene V.
Published: January 2025

Functional annotation of proteins encoded in newly sequenced genomes can be expected to meet two conflicting objectives: (i) provide as much information as possible, and (ii) avoid erroneous functional assignments and over-predictions. The continuing exponential growth of the number of sequenced genomes makes the quality of sequence annotation a critical factor in the efforts to utilize this new information. When dubious functional assignments are used as a basis for subsequent predictions, they tend to proliferate, leading to "database explosion". It is therefore important to identify the common factors that hamper functional annotation. As a first step towards that goal, we have compared the annotations of the Mycoplasma genitalium and Methanococcus jannaschii genomes produced in several independent studies. The most common causes of questionable predictions appear to be: i) non-critical use of annotations from existing database entries; ii) taking into account only the annotation of the best database hit; iii) insufficient masking of low complexity regions (e.g. non-globular domains) in protein sequences, resulting in spurious database hits obscuring relevant ones; iv) ignoring multi-domain organization of the query proteins and/or the database hits; v) non-critical functional inferences on the basis of the functions of neighboring genes in an operon; vi) non-orthologous gene displacement, i.e. involvement of structurally unrelated proteins in the same function. These observations suggest that case by case validation of functional annotation by expert biologists remains crucial for productive genome analysis.
An Evolutionary Classification of the Metallo-ß-Lactamase Fold Proteins
Authors: Aravind L.
Published: January 2025

All the detectable metallo-â-lactamase fold proteins were identified in the publicly available sequence databases and complete genome sequences using iterative profile searches with the PSI-BLAST program and motif searches with position specific weight matrices. The catalytic site/mechanism and the corresponding structural elements were characterized for these proteins based on the available structure of the Bacillus zinc-dependent â-lactamase. Based on pair-wise sequence and phylogenetic analysis an evolutionary classification for enzymes of this fold was developed and discussed in terms of implications for substrate specificity. Finally, some predicted inactive members which have been recruited for non-enzymatic functions such as microtubule binding in a cytoskeletal MAP1 are described.
Comparative Analysis of the Arabidopsis and Rice Expressed	Sequence Tag (EST) Sets
Authors: Ewing Rob , Poirot Olivier , Claverie Jean-Michel
Published: January 2025

Large numbers of expressed sequence tags (ESTs) have now been generated from a variety of model organisms.  In plants, substantial collections of ESTs are available for Arabidopsis and rice, in each case representing significant proportions of the estimated total numbers of genes.  Large-scale comparisons of Arabidopsis and rice sequences are especially interesting due to the fact that these two species are representatives of the two subclasses of the flowering plants (Dicotyledonae and Monocotyledonae, respectively).  Here we present the results of systematic analysis of the Arabidopsis and rice EST sets.  Non-redundant sets of sequences from Arabidopsis and rice were first separately derived and then combined so that gene families in common between the two species could be identified.  Our results show that 58% of non-singleton ESTs are derived from genes in gene families common to the two species.  These gene families constitute the basis of a core set of higher plant genes.
Motif Detection in Arabidopsis: Correlation	with Gene Expression Data
Authors: Janaki Chintalapati , Joshi Rajendra R.
Published: January 2025

The genes having similar expression profiles are considered to have common regulatory mechanisms and are controlled by the binding of transcription factors to the regulatory elements present in their upstream regions. The detection of cis-regulatory elements can help in further understanding of co-expression of genes. This paper deals with the detection of motifs in the upstream regions of genes involved in diurnal rhythms of Arabidopsis and also deals with the correlation of expression data with sequence information. We detected motifs in the upstream regions of genes involved in diurnal cycles and checked for their presence in circadian regulated, dark induced and in light induced genes of Arabidopsis. Ten motifs were reported in this study, out of which five were already reported in available transcription factor databases as the elements involved in light responsiveness. Significance study of ten motifs was done by taking random sets of same data size. One of the ten motifs namely GGCCCA, which was found without any base variations in 62 genes, was further studied by analyzing the expression profiles of its respective genes within the set of diurnal regulated genes using SOM clustering method. It was found that the genes were clustered together into two major groups, out of which one group had glycine rich proteins and the second group had genes belonging to dehydrogenase and oxidoreductase family.
Canonical Sensitivities: A Useful Tool to Deal with Large	Perturbations in Metabolic Network Modeling
Authors: Guebel Daniel V.
Published: January 2025

The dynamic range of metabolic models can be extended to deal with large perturbations by introducing the related concepts of "generalized" kinetic order and "canonical" sensitivities. Generalized kinetic orders are built as a well-defined non linear combination of the canonical sensitivities coefficients, which in turn are obtained by a least-squares regression on central composite factorial design data. In a such way, the whole domain of the operating variables is mapped without need to determine locally neither the first nor the second order model derivatives. The method was validated through numerical simulations, its predictions being compared with those coming from a Michaelis-Menten formalism taken as reference. In parallel, two variants of the Power-law formalism (S-system, least-squares GMA) also were tested. The canonical sensitivities method produced the widest range to predict metabolite concentrations and metabolic fluxes at the steady states. In addition, the variation pattern for the logarithmic gains and for the characteristic eigenvalues have been accurately determined from a unique overall model, being both required to make realistic analysis in metabolic engineering. The achieved information also can be expressed in terms of those typical coefficients derived from the Metabolic Control Analysis (MCA). Even if current first order Power-law or MCA formalisms were used, the canonical sensitivities approach provides a significant advantage, since complete sets of homologous, accurate, locally valid metabolic coefficients can be simultaneously recovered from the array proposed, being representative of the whole range of the operating variables instead of a unique nominal condition as is usual.
CombAlign: A Protein Sequence Comparison Algorithm Considering	Recombinations
Authors: Wegner Katja , Jansen Stephan , Wuchty Stefan , Gauges Ralph , Kummer Ursula
Published: January 2025

The basic linear treatment of sequence comparisons limits the ability of contemporary sequence alignment algorithms to detect non-order-conserving recombinations. Here, we introduce the algorithm combAlign which addresses the assessment of pairwise sequence similarity on non-order-conserving recombinations on a large scale. Emphasizing a two-level approach, combAlign first detects locally well conserved subsequences in a target and a source sequence. Subsequently, the relative placement of alignments is mapped to a graph. Concatenating local alignments to reassemble the target sequence to the fullest extent, the maximum scoring path through the graph denotes the best attainable combAlignment. Parameters influencing this process can be set to meet the user's specific demands. combAlign is applied to examples demonstrating the possibility to reflect evolutionary kinship of proteins even if their domains and motifs are strongly rearranged.
Constructing Biological Pathway Models with Hybrid Functional	Petri Nets
Authors: Doi Atsushi , Fujita Sachie , Matsuno Hiroshi , Nagasaki Masao , Miyano Satoru
Published: January 2025

In many research projects on modeling and analyzing biological pathways, the Petri net has been recognized as a promising method for representing biological pathways. From the pioneering works by Reddy et al., 1993, and Hofestädt, 1994, that model metabolic pathways by traditional Petri net, several enhanced Petri nets such as colored Petri net, stochastic Petri net, and hybrid Petri net have been used for modeling biological phenomena. Recently, Matsuno et al., 2003b, introduced the hybrid functional Petri net (HFPN) in order to give a more intuitive and natural modeling method for biological pathways than these existing Petri nets. Although the paper demonstrates the effectiveness of HFPN with two examples of gene regulation mechanism for circadian rhythms and apoptosis signaling pathway, there has been no detailed explanation about the method of HFPN construction for these examples. The purpose of this paper is to describe method to construct biological pathways with the HFPN step-by-step. The method is demonstrated by the well-known glycolytic pathway controlled by the lac operon gene regulatory mechanism.
Modeling and Simulation of Biological Systems with	Stochasticity
Authors: Meng Tan Chee , Somani Sandeep , Dhar Pawan
Published: January 2025

Mathematical modeling is a powerful approach for understanding the complexity of biological systems. Recently, several successful attempts have been made for simulating complex biological processes like metabolic pathways, gene regulatory networks and cell signaling pathways. The pathway models have not only generated experimentally verifiable hypothesis but have also provided valuable insights into the behavior of complex biological systems. Many recent studies have confirmed the phenotypic variability of organisms to an inherent stochasticity that operates at a basal level of gene expression. Due to this reason, development of novel mathematical representations and simulations algorithms are critical for successful modeling efforts in biological systems. The key is to find a biologically relevant representation for each representation. Although mathematically rigorous and physically consistent, stochastic algorithms are computationally expensive, they have been successfully used to model probabilistic events in the cell. This paper offers an overview of various mathematical and computational approaches for modeling stochastic phenomena in cellular systems.
A Novel Genomics Approach for the Identification of Drug Targets	in Pathogens, with Special Reference to Pseudomonas	Aeruginosa
Authors: Sakharkar Kishore R. , Sakharkar Meena K. , Chow Vincent T.K.
Published: January 2025

Complete genome sequences of several pathogenic bacteria have been determined, and many more such projects are currently under way. While these data potentially contain all the determinants of host-pathogen interactions and possible drug targets, computational tools for selecting suitable candidates for further experimental analyses are currently limited. Detection of bacterial genes that are non-homologous to human genes, and are essential for the survival of the pathogen represents a promising means of identifying novel drug targets. We have used three-way genome comparisons to identify essential genes from Pseudomonas aeruginosa. Our approach identified 306 essential genes that may be considered as potential drug targets. The resultant analyses are in good agreement with the results of systematic gene deletion experiments. This approach enables rapid potential drug target identification, thereby greatly facilitating the search for new antibiotics. These results underscore the utility of large genomic databases for in silico systematic drug target identification in the post-genomic era.
Thermo-Search: Lifestyle and Thermostability Analysis
Authors: Farias Savio T. , van der Linden Marx G. , Rêgo Thais G. , Araújo Demétrius A.M. , Bonato Maria Christina M.
Published: January 2025

Thermo-search is an online web tool for the analysis of proteomes and individual proteins according to the ratio of two couplets of preferred and avoided amino acids in hyperthermophiles, thermophiles and mesophiles. It displays the ratio between glutamic acid plus lysine (E+K) and glutamine plus histidine (Q+H), which is higher in thermophilic proteomes and thermostable proteins than in mesophilic proteomes and thermo labile proteins. Thermo-search allows a rapid screen of the CRM database for thermostable proteins in their functional categories and a visualization of the (E+K)/(Q+H) average ratio between organisms, allowing a comparison of their lifestyles.
Genome-Wide Prediction and Analysis of Function-Specific Transcription Factor Binding Sites
Authors: Long Fan , Liu Hong , Hahn Chang , Sumazin Pavel , Zhang Michael Q. , Zilberstein Asher
Published: January 2025

DNA-binding transcription factors play a central role in transcription regulation, and the annotation of transcription-factor binding sites in upstream regions of human genes is essential for building a genome-wide regulatory network. We describe methodology to accurately predict the transcription-factor binding sites in the proximal-promoter region of function-specific genes. In order to increase the accuracy of transcription factor binding-site prediction, we rely on recent genome sequence data, known transcription factor binding-site matrices, and Gene Ontology biological-function-based gene classification. Using TRANSFAC position-frequency matrices, we detected individual and cooperating transcription-factor binding sites in proximal promoters of ENSEMBL annotated human genes. We used the over representation of detected binding sites in the proximal promoters as compared to the second exons to control specificity. We confirmed the majority of transcription-factor binding sites predicted in proximal promoters of immune-response genes with evidence from existing literature. We validated the predicted cooperation between transcription factors NF-κB and IRF in the regulation of gene expression with microarray transcript profiling data and literature-derived protein-protein interaction network. We also identified over-represented individual and pairs of transcription-factor binding sites in the proximal promoters of each Gene Ontology biological-process gene group. Our tools and analysis provide a new resource for deciphering transcription regulation in different biological paradigms.
Efficient Two-Sample Designs for Microarray Experiments with Biological Replications
Authors: Landgrebe Jobst , Bretz Frank , Brunner Edgar
Published: January 2025

In the last years, biostatistical research has begun to apply linear models and design theory to develop efficient experimental designs and analysis tools for gene expression microarray data. With two-colour microarrays, direct comparisons of RNA-targets are possible and lead to incomplete block designs. In this setting, efficient designs for simple and factorial microarray experiments have mainly been proposed for technical replicates. But for biological replicates, which are crucial to obtain inference that can be generalised to a biological population, this question has only been discussed recently and is not fully solved yet. In this paper, we propose efficient designs for independent two-sample experiments using two-colour microarrays enabling biologists to measure their biological random samples in an efficient manner to draw generalisable conclusions. We give advice for experimental situations with differing group sizes and show the impact of different designs on the variance and degrees of freedom of the test statistics. The designs proposed in this paper can be evaluated using SAS PROC MIXED or S+/R lme.
Web-Based Visualisation of the Transcriptional Control Network of Escherichia Coli
Authors: Sosa Nestor , Kremling Andreas , Ratsch Esther , Rojas Isabel
Published: January 2025

Transcription is one of the basic processes of gene expression, controlled by a complex network of biochemical reactions. Despite its importance, most work on the visualisation of biochemical networks focuses on the representation of metabolic pathways. The visualisation of the complex networks controlling transcription requires the implementation of a hierarchical approach that allows the display of the structure of each regulatory region with its transcription factors and regulated operons. This paper presents a web-based application for the visualisation of transcriptional control networks. It takes as case study the organism Escherichia coli. The definition of the visual components implemented is mainly based on those proposed by Shen-Orr et al., 2002, slightly extended to visualise complex networks.
PathoPlant®: A Database on Plant-Pathogen Interactions
Authors: Bülow Lorenz , Schindler Martin , Choi Claudia , Hehl Reinhard
Published: January 2025

Pathogen recognition and signal transduction during plant pathogenesis is essential for the activation of plant defense mechanisms. To facilitate easy access to published data and to permit comparative studies of different pathogen response pathways, a database is indispensable to give a broad overview of the components and reactions so far known. PathoPlant® has been developed as a relational database to display relevant components and reactions involved in signal transduction related to plant-pathogen interactions. On the organism level, the tables 'plant', 'pathogen' and 'interaction' are used to describe incompatible interactions between plants and pathogens or diseases. On the molecular level, plant pathogenesis related information is organized in PathoPlant's main tables 'molecule', 'reaction' and 'location'. Signal transduction pathways are modeled as consecutive sequences of known molecules and corresponding reactions. PathoPlant entries are linked to associated internal records as well as to entries in external databases such as SWISS-PROT, GenBank, PubMed, and TRANSFAC®. PathoPlant is available as a web-based service at http://www.pathoplant.de.
Alternatively Spliced Human Genes by Exon Skipping – A Database	(ASHESdb)
Authors: Sakharkar Meena Kishore , Perumal Bagavathi S. , Lim Yun Ping , Chern Lee Pern , Yu Yiting , Kangueane Pandjassarame
Published: January 2025

Alternative splicing of mRNA allows many gene products with different functions to be produced from a single coding sequence. Exon skipping is the most commonly known alternative splicing mechanism. A comprehensive database of alternative splicing by exon skipping is made available for the human genome data. 1,229 human genes are identified to exhibit alternative splicing by exon skipping.
Simulations of Simple Artificial Genetic Networks Reveal Features	in the Use of Relevance Networks
Authors: Lindlöf Angelica , Lubovac Zelmina
Published: January 2025

Recent research on large scale microarray analysis has explored the use of Relevance Networks to find networks of genes that are associated to each other in gene expression data. In this work, we compare Relevance Networks with other types of clustering methods to test some of the stated advantages of this method. The dataset we used consists of artificial time series of Boolean gene expression values, with the aim of mimicking microarray data, generated from simple artificial genetic networks. By using this dataset, we could not confirm that Relevance Networks based on mutual information perform better than Relevance Networks based on Pearson correlation, partitional clustering or hierarchical clustering, since the results from all methods were very similar. However, all three methods successfully revealed the subsets of co-expressed genes, which is a valuable step in identifying co-regulation.
Four Basic Symmetry Types in the Universal 7-Cluster Structure of	Microbial Genomic Sequences
Authors: Gorban Alexander N. , Popova Tatyana G. , Zinovyev Andrei Y.
Published: January 2025

Coding information is the main source of heterogeneity (non-randomness) in the sequences of microbial genomes. The heterogeneity corresponds to a cluster structure in triplet distributions of relatively short genomic fragments (200–400 bp). We found a universal 7-cluster structure in microbial genomic sequences and explained its properties. We show that codon usage of bacterial genomes is a multi-linear function of their genomic G+C-content with high accuracy. Based on the analysis of 143 completely sequenced bacterial genomes available in Genbank in August 2004, we show that there are four "pure" types of the 7-cluster structure observed. All 143 cluster animated 3D-scatters are collected in a database which is made available on our web-site (http://www.ihes.fr/~zinovyev/7clusters). The findings can be readily introduced into software for gene prediction, sequence alignment or microbial genomes classification.
CBCAnalyzer: Inferring Phylogenies Based on Compensatory Base	Changes in RNA Secondary Structures
Authors: Wolf Matthias , Friedrich Joachim , Dandekar Thomas , Müller Tobias
Published: January 2025

The CBCAnalyzer (CBC = compensatory base change) is a custom written software toolbox consisting of three parts, CTTransform, CBCDetect, and CBCTree. CTTransform reads several ct-file formats, and generates a so called "bracket-dot-bracket" format that typically is used as input for other tools such as RNAforester, RNAmovie or MARNA. The latter one creates a multiple alignment based on primary sequences and secondary structures that now can be used as input for CBCDetect. CBCDetect counts CBCs in all against all of the aligned sequences. This is important in detecting species that are discriminated by their sexual incompatibility. The count (distance) matrix obtained by CBCDetect is used as input for CBCTree that reconstructs a phylogram by using the algorithm of BIONJ. In this note we describe the features of the toolbox as well as application examples. The toolbox provides a graphical user interface. It is written in C++ and freely available at: http://cbcanalyzer.bioapps.biozentrum.uni-wuerzburg.de.
Nomenclature-Based Data Retrieval without Prior Annotation:	Facilitating Biomedical Data Integration with Fast Doublet Matching
Authors: Berman Jules J.
Published: January 2025

Assigning nomenclature codes to biomedical data is an arduous, expensive and error-prone task. Data records are coded to to provide a common representation of contained concepts, allowing facile retrieval of records via a standard terminology. In the medical field, cancer registrars, nurses, pathologists, and private clinicians all understand the importance of annotating medical records with vocabularies that codify the names of diseases, procedures, billing categories, etc. Molecular biologists need codified medical records so that they can discover or validate relationships between experimental data and clinical data.

This paper introduces a new approach to retrieving data records without prior coding. The approach achieves the same result as a search over pre-coded records. It retrieves all records that contain any terms that are synonymous with a user's query-term. A recently described fast algorithm (the doublet method) permits quick iterative searches over every synonym for any term from any nomenclature occurring in a dataset of any size.

As a demonstration, a 105+ Megabyte corpus of Pubmed abstracts was searched for medical terms. Query terms were matched against either of two vocabularies and expanded as an array of equivalent search items. A single search term may have over one hundred nomenclature synonyms, all of which were searched against the full database. Iterative searches of a list of concept-equivalent terms involves many more operations than a single search over pre-annotated concept codes. Nonetheless, the doublet method achieved fast query response times (0.05 seconds using Snomed and 5 seconds using the Developmental Lineage Classification of Neoplasms, on a computer with a 2.89 GHz processor).

Pre-annotated datasets lose their value when the chosen vocabulary is replaced by a different vocabulary or by a different version of the same vocabulary. The doublet method can employ any version of any vocabulary with no pre-annotation. In many instances, the enormous effort and expense associated with data annotation can be eliminated by on-the-fly doublet matching.

The algorithm for nomenclature-based database searches using the doublet method is described. Perl scripts for implementing the algorithm and testing execution speed are provided as open source documents available from the Association for Pathology Informatics (www.pathologyinformatics.org/informatics_r.htm).
Evolutionary Analysis of Human Vascular Endothelial Growth Factor,	Angiopoietin, and Tyrosine Endothelial Kinase Involved in Angiogenesis and	Immunity
Authors: Dormer Anton , Beck Gregory
Published: January 2025

Human vascular endothelial growth factor (VEGF), angiopoietin (ANG) and tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE)-2 consist of a grouping of proteins that are involved in vascular homeostasis, vascular integrity and angiogenesis. There are nine proteins in the immediate VEGF family: VEGFA, VEGFB, VEGFC, VEGFD, VEGF-3, placental growth factor (PGF), VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-1-related. They can be stimulated by cytokines to become involved in immune responses. By using in silico tools, we were able to identify several possible analogues or homologues of VEGF, ANG and TIE-2 in invertebrates. This is the first report to show that these proteins may be conserved through evolution. These proteins may have a role in vascular maintenance and immunity. In addition, since VEGF, ANG and TIE-2 have a role in mammalian immunity that is significantly influenced by cytokines, such as IL-1, this may indicate an interaction of the vascular system and the immune system over evolutionary time.
An Analysis on Gene Architecture in Human and Mouse Genomes
Authors: Sakharkar Meena Kishore , Perumal Bagavathi S. , Sakharkar Kishore R. , Kangueane Pandjassarame
Published: January 2025

A comparative genome analysis on exon-intron distribution profiles is performed for human and mouse genomes to deduce similarities and differences between them. Interestingly, both in human and mouse genomes, the total length in introns and intergenic DNA on each chromosome is significantly correlated to the chromosome size. The results presented provide a framework for understanding the nature and patterns of exon-intron length distributions, the constraints on them and their role in genome design and evolution.
MOLS – A Program to Explore the Potential Energy Surface of a	Peptide and Locate Its Low Energy Conformations
Authors: Prasad Pandurangan Arun , Vengadesan Krishnan , Gautham Namasivayam
Published: January 2025

We describe a computer program that uses mutually orthogonal Latin squares (MOLS) to perform an efficient and exhaustive conformational search of the multi-dimensional potential energy hypersurface of an oligopeptide, and locate all its low energy conformations. The software package has been developed with a user-friendly graphical interface using the Fast Light Tool Kit (FLTK) – a cross platform C++ toolkit.
Folded RNA from an Intron of One Gene Might Inhibit Expression of	a Counteracting Gene
Authors: Jeffries Clark , Jarstfer Michael , Perkins Diana O.
Published: January 2025

Homeostatic maintenance of mRNA levels including prompt availability of mRNAs for translation in response to changing protein demands might be partly enabled by a system of combinatorial controls involving noncoding RNA blocking agents. This article proposes a specific version of that control mechanism, namely, a double-stranded RNA folding from transcription of an intron of one gene might and leading to an agent that inhibits mRNA of a counteracting gene. Thus transcription of the first gene would automatically repress translation of the second.

On the basis of a bioinformatics search, we suggest a possible example, namely, that pro-apoptosis gene PAR4 might inhibit anti-apoptosis gene XIAP. Part of an intron from PAR4 folds to form a large, stable hairpin, and reverse complement of the hairpin stem (with ∼280 nucleotides) matches a sub-sequence of an exon in XIAP. This would be part of an efficient system to drive initiated apoptosis to its conclusion. Figuratively speaking, it replaces two control knobs with one.

Since repeats, some with many thousands of copies, occur throughout the genome with complex distributions, care must be taken before asserting that the presence of any repeat in any gene is significant. Our apoptosis example involves repeats, so experimental verification is needed and planned. However, if it is found that the noncoding RNA by-product of one gene folds into a hairpin that is processed into an agent that inhibits a counteracting gene, then the same type of control unit might be found extensively among counteracting families of genes of many types.
CMDWave: Conserved Motifs Detection Using Wavelets
Authors: Riaz Tariq , Li Kuo-Bin , Tang Francis , Krishnan Arun
Published: January 2025

CMDWave (Conserved Motif Detection using WAVElets) is a web server that predicts conserved motifs in protein sequences. A set of query protein sequences are first aligned using ClustalW to obtain equal sized sequences. CMDWave then converts the sequences into a numerical representation using electron-ion interaction potential (EIIP). This is followed by a wavelet decomposition and reconstruction. A new similarity metric along with thresholding is then used to identify conserved motifs across all the query sequences. Users need not specify the number of motifs to be identified. For larger groups of sequences, results can be emailed to the users.
Accessing Optimal Primer Distance from Insert
Authors: Prosdocimi Francisco , Ortega J. Miguel
Published: January 2025

When building either DNA or cDNA libraries, a researcher looks at the vector multiple cloning site and chooses which restriction enzyme(s) will be used to clone the inserts. Although this procedure does not seem to be important, the accurate choosing of primer to insert distance can save time and money from genome and transcriptome projects. Here, 846 single-pool pUC18 sequences were produced and compared with the pUC18 consensus using local alignment tools. Data show that reads often contain 0–20 miscalled bases at the beginning of read and noise to signal transition is frequently found at 46–54 bases from the first 3' base downstream the sequencing primer. For SWAT-based approaches, 60 bases was the distance where over 90% of the sequences provided reliable information, presenting 13 vector bases on average. Looking at the data, it is possible to choose the most appropriate primer to insert distance for many applications.
The Wave Phenomena in Smooth Muscle Syncytia
Authors: Miftahof Roustem N.
Published: January 2025

Based on the concept of a functional unit, a mathematical model of a segment of the gut is developed. The model comprises real anatomical, histomorphological, physiological, and pharmacological information on the function of the organ. Numerical investigation into the dynamics of the electromechanical wave phenomenon reveals the fundamental principles of wave initiation, formation, and propagation along electrically anisotropic longitudinal and isotropic circular smooth muscle syncytia. A pattern of self-sustained electrical activity with the formation of spiral waves is discovered in the longitudinal syncytia and is attributed to the change in conductivity in the syncytia as a result of mechanical deformation of smooth muscle fibers. The model adequately predicts the effects of pharmacological interventions on the dynamics of myoelectrical activity. Although no direct experimental comparison to the theoretical findings is possible at this stage, the proposed mathematical model provides new insight onto the basics of physiological processes – slow wave activity, electromechanical conjugation, etc. – and a clinical entity – gastrointestinal dysrhythmias.
Computing TaqMan Probes for Multiplex PCR Detection of	E. coli O157 Serotypes in Water
Authors: Ram Siya , Shanker Rishi
Published: January 2025

Diarrheagenic E. coli strains contribute to water related diseases in urban and rural environment in developing and developed world. E. coli pathotype and pathogenicity varies due to complex multifactorial mechanism involving a large number of virulence factors. Rapid assessment of the virulence pattern of E. coli isolates is possible by Real-Time PCR probes like TaqMan. For designing TaqMan probes and primers for multiplex PCR selected E. coli gene sequences: stx1, stx2, hlyA, chuA, eae, lacZ, lamB and fimA were retrieved from NCBI's GenBank database. The alignment of the multiple sequences and analysis of conserved sequences was carried out using ClustalW and BLAST programs. The primers and Taqmen probes were designed using Beacon Designer software version 2.1 for two multiplexed PCR assays. In silico PCR simulation of these assays showed PCR products for stx2 (248 bp) stx1 (102 bp), lacZ (228bp) and lamB (86 bp) in multiplex #1 and eae (200 bp), chuA (147 bp), hlyA (141bp) and fimA (79 bp) in multiplex #2, respectively. These multiplexed PCR amplification products and probes can be used to identify and confirm presence of O157:H7/H7-, O157:H43/45 and O26:H $^{-}$ /H11 serotypes. In conclusion, multiplex Real-Time Polymerase Chain Reaction oligomers and TaqMan probes designed and validated in silico will be helpful in management of water quality and outbreaks, by improving specificity and minimizing time needed for in vitro verification work.
Molecular Analysis of A 348 Base-Pair Segment of Open Reading	Frame 2 of Human Astrovirus. A Characterization of Colombian Isolates
Authors: Ulloa Juan Carlos , Matiz Adriana , Lareo Leonardo , Gutiérrez Maria Fernanda
Published: January 2025

We are reporting computational studies of several genotyped strains of astrovirus isolated in Colombia which we have genotyped using the 348-bp segment located between nucleotides 258 and 606 close to the amino terminal region of the complete ORF 2. By biocomputational techniques this 348-bp segment from the different strains was translated into an amino acid sequence. The sequences were aligned and compared in order to build a dendrogram. Our results show that the 348 bp and the 116 amino acid peptides cluster in a very conservative way, showing slight genetic variations between them. This slight sequence variability does not allow us to identify common amino acid substitution patterns shared by all members of each HAstV specific type, thus suggesting that antigenic epitopes are probably located outside the 116 peptide fragment of this capsid protein. These results show that there is little recombination among different regions of the ORF2, thus suggesting that this genotyping method should continue to be useful for serotyping HAstV isolates.
In Silico Discrimination of Single Nucleotide	Polymorphisms and Pathological Mutations in Human Gene Promoter Regions by	Means of Local DNA Sequence Context and Regularity
Authors: Khan Imtiaz A. , Mort Matthew , Buckland Paul R. , O'Donovan Michael C. , Cooper David N. , Chuzhanova Nadia A.
Published: January 2025

DNA sequence features were sought that could be used for the in silico ascertainment of the likely functional consequences of single nucleotide changes in human gene promoter regions. To identify relevant features of the local DNA sequence context, we transformed into consensus tables the nucleotide composition of sequences flanking 101 promoter SNPs of type C↔T or A↔G, defined empirically as being either 'functional' or 'non-functional' on the basis of a standardised reporter gene assay. The similarity of a given sequence to these consensus tables was then measured by means of the Shapiro-Senapathy score. A decision rule with the potential to discriminate between empirically ascertained functional and non-functional SNPs was proposed that potentiated discrimination between functional and non-functional SNPs with a sensitivity of 80% and a specificity of 20%. Two further datasets (viz. disease-associated SNPs of types A↔G and C↔T (N=75) and pathological promoter mutations (transitions, N=114)) were retrieved from the Human Gene Mutation Database (HGMD; http://www.hgmd.org/) and analyzed using consensus tables derived from the functional and non-functional promoter SNPs; ∼70% were correctly recognized as being of probable functional significance. Complexity analysis was also used to quantify the regularity of the local DNA sequence environment. Functional SNPs/mutations of type C↔T were found to occur in DNA regions characterized by lower average sequence complexity as measured with respect to symmetric elements; complexity values increased gradually from functional SNPs and pathological mutations to functional disease-associated SNPs and non-functional SNPs. This may reflect the internal axial symmetry that frequently characterizes transcription factor binding sites.
GPAC: Benchmarking the Sensitivity of Genome Informatics Analysis	to Genome Annotation Completeness
Authors: Arakawa Kazuharu , Nakayama Yoichi , Tomita Masaru
Published: January 2025

In view of the recent explosion in genome sequence data, and the 200 or more complete genome sequences currently available, the importance of genome-scale bioinformatics analysis is increasing rapidly. However, computational genome informatics analyses often lack a statistical assessment of their sensitivity to the completeness of the functional annotation. Therefore, a pre-analysis method to automatically validate the sensitivity of computational genome analyses with regard to genome annotation completeness is useful for this purpose. In this report we developed the Gene Prediction Accuracy Classification (GPAC) test, which provides statistical evidence of sensitivity by repeating the same analysis for five different gene groups (classified according to annotation accuracy level), and for randomly sampled gene groups, with the same number of genes as each of the five classified groups. Variability in these results is then assessed, and if the results vary significantly with different data subsets, the analysis is considered "sensitive" to annotation completeness, and careful selection of data is advised prior to the actual in silico analysis. The GPAC test has been applied to the analyses of Sakai et al., 2001, and Ohno et al., 2001, and it revealed that the analysis of Ohno et al. was more sensitive to annotation completeness. It showed that GPAC could be employed to ascertain the sensitivity of an analysis. The GPAC benchmarking software is freely available in the latest G-language Genome Analysis Environment package, at http://www.g-language.org/.
Gene Knockout Experiments to Quantify a G2/M Genetic Network	Simulation for Mammary Cancer Susceptibility
Authors: Bankhead III Armand , Magnuson Nancy S. , Heckendorn Robert B.
Published: January 2025

A G2/M genetic network simulation is trained with tumor incidence data from knockout experiments. The genetic network is implemented using a neural network; knockout genotypes are simulated by removing nodes in the neural network. Two analyses are used to interpret the resulting network weights. We use a novel approach of fixing the network topology that allows knockout TSG (tumor suppressor gene) data from multiple studies to overlap and indirectly inform one another. The trained simulation is validated by reproducing qualitative mammary cancer susceptibilities of ATM, BRCA1, and p53 TSGs. The work described is valuable because it allows TSG mammary cancer susceptibility to be quantified using genetic network topology and in vivo knockout data.
Are Categorical Periodograms and Indicator Sequences of Genomes	Spectrally Equivalent?
Authors: Nair Achuthsankar S. , Mahalakshmi T.
Published: January 2025

This paper reports a novel symbol-to-signal mapping for DNA sequences, based on the concept of categorical periodograms. A categorical periodogram is a numeric sequence with the n-th element of the sequence indicating the number of occurrences of cycles with period n in it. The period of the cycle is defined as the number of intervening events plus one. Spectral analysis studies have been conducted on Cumulative Categorical Periodogram (CCP) of 10 genes from the data set of Burset and Guigo. It is observed that the spectral signatures in CCP are functionally equivalent to the established N/3 peak in the spectrum of indicator sequences of genomes. Being a single sequence compared to four sequences in the case of indicator sequence representation, the method is claimed to be functionally equivalent, but computationally better for identification of gene coding regions in sequences.
AthaMap: From in silico Data to Real	Transcription Factor Binding Sites
Authors: Bülow Lorenz , Steffens Nils Ole , Galuschka Claudia , Schindler Martin , Hehl Reinhard
Published: January 2025

AthaMap generates a map for cis-regulatory sequences for the whole Arabidopsis thaliana genome. AthaMap was initially developed by matrix-based detection of putative transcription factor binding sites (TFBS) mostly determined from random binding site selection experiments. Now, also experimentally verified TFBS have been included for 48 different Arabidopsis thaliana transcription factors (TF). Based on these sequences, 89,416 very similar putative TFBS were determined within the genome of A. thaliana and annotated to AthaMap. Matrix- and single sequence-based binding sites can be included in colocalization analysis for the identification of combinatorial cis-regulatory elements. As an example, putative target genes of the WRKY18 transcription factor that is involved in plant-pathogen interaction were determined. New functions of AthaMap include descriptions for all annotated Arabidopsis thaliana genes and direct links to TAIR, TIGR and MIPS. Transcription factors used in the binding site determination are linked to TAIR and TRANSFAC® databases. AthaMap is freely available at http://www.athamap.de.
Basic Faced α-Helices are Widespread in the Peptide	Extensions of the Eukaryotic Aminoacyl-tRNA Synthetases
Authors: Massey Steven E.
Published: January 2025

Three aminoacyl-tRNA synthetases from yeast, one from plants and one from mammals possess unusual structures at their N termini, namely α helices with basic residues distributed asymmetrically, on a single face of the helix. It is unknown if these 'basic faced' α helices (BFAHs) are unique to the aminoacyl-tRNA synthetases. Analysis of the amino acid sequences of these five aminoacyl-tRNA synthetases using the hydrophobic moment algorithm failed to accurately identify the BFAHs. A new algorithm was therefore developed, called the 'basic moment'. This is a Fourier analysis procedure that predicts the distribution of basic residues within protein secondary structure. The basic moment identifies with a high degree of accuracy the five known BFAHs and also identifies further potential BFAHs at evolutionarily conserved positions in the peptide extensions of aspartyl-, lysyl- and valyl- tRNA synthetases from a range of eukaryotic species. In addition, the algorithm identifies the two-helix pair tRNA binding domain of alanyl-tRNA synthetase, implying that the domain includes a BFAH. The functional and evolutionary aspects of these structural features are discussed.
Huge Proteins in The Human Proteome and Their Participation in	Hereditary Diseases
Authors: Sakharkar Meena Kishore , Kangueane Pandjassarame , Sakharkar Kishore Ramaji , Zhong Zhaowei
Published: January 2025

Protein lengths vary considerably from a few to thousands of amino acids and length variations are documented to have multiple effects. A computational approach to investigate the functional impact of protein length variation in genetic disorders is presented. The genes for huge proteins are found to have more introns. Our analysis also shows greater involvement of huge proteins in hereditary diseases.