PrimerIdent: A web based tool for conserved primer design

Conserved primers across multiple species and simultaneously specific for a certain isozyme can be rare and difficult to find. PrimerIdent was developed aiming to automate this primer design and selection process in a given nucleotide sequence alignment, providing an intuitive, easy to interpret graphical result, which offers a list of all possible primers that meet the user criteria, with a colour-code identity to each sequence in the alignment. The software here presented is a simple and intuitive web based tool that is suitable for distinguishing very similar nucleotide sequences, such as isozymes-coding sequences, to enable the conserved primer design across multiple species, necessary for approaches that rely on knowing if a primer is suitable for a certain set of pre-aligned sequences, to design a specific primer to a certain sequence variation, or a combination thereof. This extremely useful software can, therefore, be used as a tool for the specific amplification of individual members of multigenic families across related species and also to evaluate the differential expression of isogenes for a given species. AVAILABILITY: http://primerident.up.pt.     

OrFin: A web tool for detection of putative orthologs

Identification of ortholog is one of the important tasks to understand a novel genome. It helps to assign functional annotations, from one organism to another organism. To identify the putative ortholog, Reciprocal Best BLAST hit (RBBH) method is known to be an efficient approach. OrFin makes use of the same approach to identify pair of orthologous proteins for a given set of sequences of two species. It is a user-friendly web tool which works with user defined parameters to search RBBHs. Results are produced in both html and text format.

Availability

This web tool is freely available at http://bifl.uohyd.ac.in/orfin     

A vector projection method for predicting supersecondary motifs

For the 11 types of most frequently occurring supersecondary motifs, we used a new method—the vector projection method—to predict a protein's supersecondary structure. In a training set of peptides and a test set of peptides we obtained a satisfactory result, with a prediction accuracy of about 90%. The high prediction accuracy indicates that this method is reasonable for predicting the folding motifs of proteins. This work provides insight into the problem of predicting a protein's local structure accurately, and is of particular value in protein modeling, prediction, and molecule design.     

CREDO: a web-based tool for computational detection of conserved sequence motifs in noncoding sequences

SUMMARY: CREDO is a user-friendly, web-based tool that integrates the analysis and results of different algorithms widely used for the computational detection of conserved sequence motifs in noncoding sequences. It enables easy comparison of the individual results. CREDO offers intuitive interfaces for easy and rapid configuration of the applied algorithms and convenient views on the results in graphical and tabular formats. AVAILABILITY: http://mips.gsf.de/proj/regulomips/credo.htm.     

iLIR@viral: A web resource for LIR motif-containing proteins in viruses

Macroautophagy/autophagy has been shown to mediate the selective lysosomal degradation of pathogenic bacteria and viruses (xenophagy), and to contribute to the activation of innate and adaptative immune responses. Autophagy can serve as an antiviral defense mechanism but also as a proviral process during infection. Atg8-family proteins play a central role in the autophagy process due to their ability to interact with components of the autophagy machinery as well as selective autophagy receptors and adaptor proteins. Such interactions are usually mediated through LC3-interacting region (LIR) motifs. So far, only one viral protein has been experimentally shown to have a functional LIR motif, leaving open a vast field for investigation. Here, we have developed the iLIR@viral database (http://ilir.uk/virus/) as a freely accessible web resource listing all the putative canonical LIR motifs identified in viral proteins. Additionally, we used a curated text-mining analysis of the literature to identify novel putative LIR motif-containing proteins (LIRCPs) in viruses. We anticipate that iLIR@viral will assist with elucidating the full complement of LIRCPs in viruses.     

iLIR database: A web resource for LIR motif-containing proteins in eukaryotes

Atg8-family proteins are the best-studied proteins of the core autophagic machinery. They are essential for the elongation and closure of the phagophore into a proper autophagosome. Moreover, Atg8-family proteins are associated with the phagophore from the initiation of the autophagic process to, or just prior to, the fusion between autophagosomes with lysosomes. In addition to their implication in autophagosome biogenesis, they are crucial for selective autophagy through their ability to interact with selective autophagy receptor proteins necessary for the specific targeting of substrates for autophagic degradation. In the past few years it has been revealed that Atg8-interacting proteins include not only receptors but also components of the core autophagic machinery, proteins associated with vesicles and their transport, and specific proteins that are selectively degraded by autophagy. Atg8-interacting proteins contain a short linear LC3-interacting region/LC3 recognition sequence/Atg8-interacting motif (LIR/LRS/AIM) motif which is responsible for their interaction with Atg8-family proteins. These proteins are referred to as LIR-containing proteins (LIRCPs). So far, many experimental efforts have been carried out to identify new LIRCPs, leading to the characterization of some of them in the past 10 years. Given the need for the identification of LIRCPs in various organisms, we developed the iLIR database (https://ilir.warwick.ac.uk) as a freely available web resource, listing all the putative canonical LIRCPs identified in silico in the proteomes of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO) term analysis. Additionally, a curated text-mining analysis of the literature permitted us to identify novel putative LICRPs in mammals that have not previously been associated with autophagy.     

Prediction of MHC binding peptide using Gibbs motif sampler,weight matrix and artificial neural network

The identification of MHC restricted epitopes is an important goal in peptide based vaccine and diagnostic development. As wet lab experiments for identification of MHC binding peptide are expensive and time consuming, in silico tools have been developed as fast alternatives, however with low performance. In the present study, we used IEDB training and blind validation datasets for the prediction of peptide binding to fourteen human MHC class I and II molecules using Gibbs motif sampler, weight matrix and artificial neural network methods. As compare to MHC class I predictor based on sequence weighting (Aroc=0.95 and CC=0.56) and artificial neural network (Aroc=0.73 and CC=0.25), MHC class II predictor based on Gibbs sampler did not perform well (Aroc=0.62 and CC=0.19). The predictive accuracy of Gibbs motif sampler in identifying the 9-mer cores of a binding peptide to DRB1 alleles are also limited (40¢), however above the random prediction (14¢). Therefore, the size of dataset (training and validation) and the correct identification of the binding core are the two main factors limiting the performance of MHC class-II binding peptide prediction. Overall, these data suggest that there is substantial room to improve the quality of the core predictions using novel approaches that capture distinct features of MHC-peptide interactions than the current approaches.     

SeqMaT: A sequence manipulation tool for phylogenetic analysis

Most bioinformatics tools require specialized input formats for sequence comparison and analysis. This is particularly true for molecular phylogeny programs, which accept only certain formats. In addition, it is often necessary to eliminate highly similar sequences among the input, especially when the dataset is large. Moreover, most programs have restrictions upon the sequence name. Here we introduce SeqMaT, a Sequence Manipulation Tool. It has the following functions: data format conversion,sequence name coding and decoding,redundant and highly similar sequence removal, anddata mining utilities. SeqMaT was developed using Java with two versions, web-based and standalone. A standalone program is convenient to manipulate a large number of sequences, while the web version will guarantee wide availability of the tool for researchers and practitioners throughout the Internet. AVAILABILITY: The database is available for free at http://glee.ist.unomaha.edu/seqmat.     

ClusterDraw web server: a tool to identify and visualize clusters of binding motifs for transcription factors

ClusterDraw is a program aimed to identification of binding sites and binding-site clusters. Major difference of the ClusterDraw from existing tools is its ability to scan a wide range of parameter values and weigh statistical significance of all possible clusters, smaller than a selected size. The program produces graphs along with decorated FASTA files. ClusterDraw web server is available at the following URL: http://flydev.berkeley.edu/cgi-bin/cld/submit.cgi     

Homeotic protein binding sites, origins of replication, and nuclear matrix anchorage sites share the ATTA and ATTTA motifs.

Nuclear matrix organizes the mammalian chromatin into loops. This is achieved by binding of nuclear matrix proteins to characteristic DNA landmarks in introns as well as proximal and distal sites flanking the 5' and 3' ends of genes. Matrix anchorage sites (MARs), origins of replication (ORIs), and homeotic protein binding sites share common DNA sequence motifs. In particular, the ATTA and ATTTA motifs, which constitute the core elements recognized by the homeobox domain from species as divergent as flies and humans, are frequently occurring in the matrix attachment sites of several genes. The human apolipoprotein B 3' MAR and a stretch of the Chinese hamster DHFR gene intron and human HPRT gene intron shown to anchor these genes to the nuclear matrix are mosaics of ATTA and ATTTA motifs. Several origins of replication also share these elements. This observation suggests that homeotic proteins which control the expression level of many genes and pattern formation during development are components of the nuclear matrix. Thus, the nuclear matrix, known as the site of DNA replication, might sculpture the crossroads of the differential activation of origins during development and S-phase and the control of gene expression and pattern formation in embryogenesis.     

Computational drug repositioning using similarity constrained weight regularization matrix factorization: A case of COVID‐19

Amid the COVID‐19 crisis, we put sizeable efforts to collect a high number of experimentally validated drug–virus association entries from literature by text mining and built a human drug–virus association database. To the best of our knowledge, it is the largest publicly available drug–virus database so far. Next, we develop a novel weight regularization matrix factorization approach, termed WRMF, for in silico drug repurposing by integrating three networks: the known drug–virus association network, the drug–drug chemical structure similarity network, and the virus–virus genomic sequencing similarity network. Specifically, WRMF adds a weight to each training sample for reducing the influence of negative samples (i.e. the drug–virus association is unassociated). A comparison on the curated drug–virus database shows that WRMF performs better than a few state‐of‐the‐art methods. In addition, we selected the other two different public datasets (i.e. Cdataset and HMDD V2.0) to assess WRMF''s performance. The case study also demonstrated the accuracy and reliability of WRMF to infer potential drugs for the novel virus. In summary, we offer a useful tool including a novel drug–virus association database and a powerful method WRMF to repurpose potential drugs for new viruses.     

DNA barcoding as an effective tool to complement wetland management: A case study of a protected area in Italy

In recent years, DNA barcoding has been suggested as a useful molecular technique to complement traditional taxonomic expertise for fast species identification and biodiversity inventories. In this study, in situ application of DNA barcodes was tested on the plant community of a wetland area in central Italy. Four cpDNA markers (trnH–psbA, rbcL, rpoC1, and matK) were tested on 40 plant species, 26 of which strictly connected to the aquatic habitat. Universality of the method, ease of data retrieval, and correct assignation of the genetic markers to each species were evaluated. The markers showed different prospects of reliable applicability. The obtained sequences were blasted against the NCBI database to verify the correct species identification. A score ranging between 32% and 67% was achieved. Overall, eight species remained unidentified with all the tested barcodes due to the absence of conspecific sequences in the available databases. This work demonstrates some limitations in the applicability of DNA barcoding to accomplish complete taxonomical surveys. Difficulties encountered in this study urge refinement of technical protocols and accessibility to wider databases. Future technological advances and larger sample sets will certainly reinforce DNA barcoding as a useful tool to address knowledge and conservation of wetlands.     

MCLPMDA: A novel method for miRNA‐disease association prediction based on matrix completion and label propagation

MiRNAs are a class of small non‐coding RNAs that are involved in the development and progression of various complex diseases. Great efforts have been made to discover potential associations between miRNAs and diseases recently. As experimental methods are in general expensive and time‐consuming, a large number of computational models have been developed to effectively predict reliable disease‐related miRNAs. However, the inherent noise and incompleteness in the existing biological datasets have inevitably limited the prediction accuracy of current computational models. To solve this issue, in this paper, we propose a novel method for miRNA‐disease association prediction based on matrix completion and label propagation. Specifically, our method first reconstructs a new miRNA/disease similarity matrix by matrix completion algorithm based on known experimentally verified miRNA‐disease associations and then utilizes the label propagation algorithm to reliably predict disease‐related miRNAs. As a result, MCLPMDA achieved comparable performance under different evaluation metrics and was capable of discovering greater number of true miRNA‐disease associations. Moreover, case study conducted on Breast Neoplasms further confirmed the prediction reliability of the proposed method. Taken together, the experimental results clearly demonstrated that MCLPMDA can serve as an effective and reliable tool for miRNA‐disease association prediction.     

A P-loop-like motif in a widespread ATP pyrophosphatase domain: Implications for the evolution of sequence motifs and enzyme activity

A conserved amino acid sequence motif was identified in four distinct groups of enzymes that catalyze the hydrolysis of the α–β phosphate bond of ATP, namely GMP synthetases, argininosuccinate synthetases, asparagine synthetases, and ATP sulfurylases. The motif is also present in Rhodobacter capsulata AdgA, Escherichia coli NtrL, and Bacillus subtilis OutB, for which no enzymatic activities are currently known. The observed pattern of amino acid residue conservation and predicted secondary structures suggest that this motif may be a modified version of the P-loop of nucleotide binding domains, and that it is likely to be involved in phosphate binding. We call it PP-motif, since it appears to be a part of a previously uncharacterized ATP pyrophophatase domain. ATP sulfurylases, NtrL, and OutB consist of this domain alone. In other proteins, the pyrophosphatase domain is associated with amidotransferase domains (type I or type II), a putative citrulline-aspartate ligase domain or a nitrilase/amidase domain. Unexpectedly, statistically significant overall sequence similarity was found between ATP sulfurylase and 3′-phosphoadenosine 5′-phosphosulfate (PAPS) reductase, another protein of the sulfate activation pathway. The PP-motif is strongly modified in PAPS reductases, but they share with ATP sulfurylases another conserved motif which might be involved in sulfate binding. We propose that PAPS reductases may have evolved from ATP sulfurylases; the evolution of the new enzymatic function appears to be accompanied by a switch of the strongest functional constraint from the PP-motif to the putative sulfate-binding motif. © 1994 Wiley-Liss, Inc.