Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An Exploration Into Improving DNA Motif Inference by Looking for Highly Conserved Core Regions.

ABSTRACT: Although most verified functional elements in noncoding DNA contain a highly conserved core region, this concept is not generally incorporated into de novo motif inference systems. In this work, we explore the utility of adding the notion of conserved core regions into a comparative genomics approach for the search for putative functional elements in noncoding DNA. By modifying the scoring function for GAMI, Genetic Algorithms for Motif Inference, we investigate tradeoffs between the strength of conservation of the full motif vs. the strength of conservation of a core region. This work illustrates that incorporating information about the structure of transcription factor binding sites can be helpful in identifying biologically functional elements.

SUBMITTER: Thompson JA

PROVIDER: S-EPMC6474685 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

An Exploration Into Improving DNA Motif Inference by Looking for Highly Conserved Core Regions.

Thompson Jeffrey A JA Congdon Clare Bates CB

IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology proceedings. IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology 20130401

Although most verified functional elements in noncoding DNA contain a highly conserved core region, this concept is not generally incorporated into <i>de novo</i> motif inference systems. In this work, we explore the utility of adding the notion of conserved core regions into a comparative genomics approach for the search for putative functional elements in noncoding DNA. By modifying the scoring function for GAMI, Genetic Algorithms for Motif Inference, we investigate tradeoffs between the stre ...[more]

PMID: 31008453

Similar Datasets

Motif-Aware PRALINE: Improving the alignment of motif regions.

Project description:Protein or DNA motifs are sequence regions which possess biological importance. These regions are often highly conserved among homologous sequences. The generation of multiple sequence alignments (MSAs) with a correct alignment of the conserved sequence motifs is still difficult to achieve, due to the fact that the contribution of these typically short fragments is overshadowed by the rest of the sequence. Here we extended the PRALINE multiple sequence alignment program with a novel motif-aware MSA algorithm in order to address this shortcoming. This method can incorporate explicit information about the presence of externally provided sequence motifs, which is then used in the dynamic programming step by boosting the amino acid substitution matrix towards the motif. The strength of the boost is controlled by a parameter, ?. Using a benchmark set of alignments we confirm that a good compromise can be found that improves the matching of motif regions while not significantly reducing the overall alignment quality. By estimating ? on an unrelated set of reference alignments we find there is indeed a strong conservation signal for motifs. A number of typical but difficult MSA use cases are explored to exemplify the problems in correctly aligning functional sequence motifs and how the motif-aware alignment method can be employed to alleviate these problems.

| S-EPMC6233922 | biostudies-literature

CORAL: aligning conserved core regions across domain families.

Project description:Homologous protein families share highly conserved sequence and structure regions that are frequent targets for comparative analysis of related proteins and families. Many protein families, such as the curated domain families in the Conserved Domain Database (CDD), exhibit similar structural cores. To improve accuracy in aligning such protein families, we propose a profile-profile method CORAL that aligns individual core regions as gap-free units.CORAL computes optimal local alignment of two profiles with heuristics to preserve continuity within core regions. We benchmarked its performance on curated domains in CDD, which have pre-defined core regions, against COMPASS, HHalign and PSI-BLAST, using structure superpositions and comprehensive curator-optimized alignments as standards of truth. CORAL improves alignment accuracy on core regions over general profile methods, returning a balanced score of 0.57 for over 80% of all domain families in CDD, compared with the highest balanced score of 0.45 from other methods. Further, CORAL provides E-values to aid in detecting homologous protein families and, by respecting block boundaries, produces alignments with improved 'readability' that facilitate manual refinement.CORAL will be included in future versions of the NCBI Cn3D/CDTree software, which can be downloaded at http://www.ncbi.nlm.nih.gov/Structure/cdtree/cdtree.shtml.Supplementary data are available at Bioinformatics online.

| S-EPMC2712342 | biostudies-literature

Refining multiple sequence alignments with conserved core regions.

Project description:Accurate multiple sequence alignments of proteins are very important to several areas of computational biology and provide an understanding of phylogenetic history of domain families, their identification and classification. This article presents a new algorithm, REFINER, that refines a multiple sequence alignment by iterative realignment of its individual sequences with the predetermined conserved core (block) model of a protein family. Realignment of each sequence can correct misalignments between a given sequence and the rest of the profile and at the same time preserves the family's overall block model. Large-scale benchmarking studies showed a noticeable improvement of alignment after refinement. This can be inferred from the increased alignment score and enhanced sensitivity for database searching using the sequence profiles derived from refined alignments compared with the original alignments. A standalone version of the program is available by ftp distribution (ftp://ftp.ncbi.nih.gov/pub/REFINER) and will be incorporated into the next release of the Cn3D structure/alignment viewer.

| S-EPMC1463900 | biostudies-literature

CHOP: visualization of 'wobbling' and isolation of highly conserved regions from aligned DNA sequences.

Project description:The web software CHOP was developed to visualize the 'wobbling' in the third codon position of aligned DNA sequences. The simple features of this tool allow users to easily find regions suspected of containing coding sequences (CDSs). The program also allows visualization of the nucleotide diversity between two genomic or gene sequences by graphically plotting the percentage identity between the two sequences. CHOP can also isolate highly conserved regions within both CDSs and non-CDSs. Highly conserved regions within CDSs include the regions with lower rates of synonymous substitution in which nucleotide sequences are expected to be under strong selective pressure. CHOP is available at http://bunsei2.med.u-tokai.ac.jp:8080/~ohtsuka/cds_finding.html.

| S-EPMC441586 | biostudies-literature

Less-is-more: selecting transcription factor binding regions informative for motif inference.

Project description:Numerous statistical methods have emerged for inferring DNA motifs for transcription factors (TFs) from genomic regions. However, the process of selecting informative regions for motif inference remains understudied. Current approaches select regions with strong ChIP-seq signal for a given TF, assuming that such strong signal primarily results from specific interactions between the TF and its motif. Additionally, these selection approaches do not account for non-target motifs, i.e. motifs of other TFs; they presume the occurrence of these non-target motifs infrequent compared to that of the target motif, and thus assume these have minimal interference with the identification of the target. Leveraging extensive ChIP-seq datasets, we introduced the concept of TF signal 'crowdedness', referred to as C-score, for each genomic region. The C-score helps in highlighting TF signals arising from non-specific interactions. Moreover, by considering the C-score (and adjusting for the length of genomic regions), we can effectively mitigate interference of non-target motifs. Using these tools, we find that in many instances, strong ChIP-seq signal stems mainly from non-specific interactions, and the occurrence of non-target motifs significantly impacts the accurate inference of the target motif. Prioritizing genomic regions with reduced crowdedness and short length markedly improves motif inference. This 'less-is-more' effect suggests that ChIP-seq region selection warrants more attention.

| S-EPMC10899791 | biostudies-literature

The active site of the DNA repair endonuclease XPF-ERCC1 forms a highly conserved nuclease motif.

Project description:XPF-ERCC1 is a structure-specific endonuclease involved in nucleotide excision repair, interstrand crosslink repair and homologous recombination. So far, it has not been shown experimentally which subunit of the heterodimer harbors the nuclease activity and which amino acids contribute to catalysis. We used an affinity cleavage assay and located the active site to amino acids 670-740 of XPF. Point mutations generated in this region were analyzed for their role in nuclease activity, metal coordination and DNA binding. Several acidic and basic residues turned out to be required for nuclease activity, but not DNA binding. The separation of substrate binding and catalysis by XPF-ERCC1 will be invaluable in studying the role of this protein in various DNA repair processes. Alignment of the active site region of XPF with proteins belonging to the Mus81 family and a putative archaeal RNA helicase family reveals that seven of the residues of XPF involved in nuclease activity are absolutely conserved in the three protein families, indicating that they share a common nuclease motif.

| S-EPMC125967 | biostudies-literature

A conserved three-nucleotide core motif defines Musashi RNA binding specificity.

Project description:Musashi (MSI) family proteins control cell proliferation and differentiation in many biological systems. They are overexpressed in tumors of several origins, and their expression level correlates with poor prognosis. MSI proteins control gene expression by binding RNA and regulating its translation. They contain two RNA recognition motif (RRM) domains, which recognize a defined sequence element. The relative contribution of each nucleotide to the binding affinity and specificity is unknown. We analyzed the binding specificity of three MSI family RRM domains using a quantitative fluorescence anisotropy assay. We found that the core element driving recognition is the sequence UAG. Nucleotides outside of this motif have a limited contribution to binding free energy. For mouse MSI1, recognition is determined by the first of the two RRM domains. The second RRM adds affinity but does not contribute to binding specificity. In contrast, the recognition element for Drosophila MSI is more extensive than the mouse homolog, suggesting functional divergence. The short nature of the binding determinant suggests that protein-RNA affinity alone is insufficient to drive target selection by MSI family proteins.

| S-EPMC4271237 | biostudies-literature

Pervasive, conserved secondary structure in highly charged protein regions.

Project description:Understanding how protein sequences confer function remains a defining challenge in molecular biology. Two approaches have yielded enormous insight yet are often pursued separately: structure-based, where sequence-encoded structures mediate function, and disorder-based, where sequences dictate physicochemical and dynamical properties which determine function in the absence of stable structure. Here we study highly charged protein regions (>40% charged residues), which are routinely presumed to be disordered. Using recent advances in structure prediction and experimental structures, we show that roughly 40% of these regions form well-structured helices. Features often used to predict disorder-high charge density, low hydrophobicity, low sequence complexity, and evolutionarily varying length-are also compatible with solvated, variable-length helices. We show that a simple composition classifier predicts the existence of structure far better than well-established heuristics based on charge and hydropathy. We show that helical structure is more prevalent than previously appreciated in highly charged regions of diverse proteomes and characterize the conservation of highly charged regions. Our results underscore the importance of integrating, rather than choosing between, structure- and disorder-based approaches.

| S-EPMC9949069 | biostudies-literature

Pervasive, conserved secondary structure in highly charged protein regions.

| S-EPMC10602382 | biostudies-literature

The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals.

Project description:In the Drosophila nervous system, the glial cells missing gene (gcm) is transiently expressed in glial precursors to switch their fate from the neuronal default to glia. It encodes a novel 504-amino acid protein with a nuclear localization signal. We report here that the GCM protein is a novel DNA-binding protein and that its DNA-binding activity is localized in the N-terminal 181 amino acids. It binds with high specificity to the nucleotide sequence, (A/G)CCCGCAT, which is a novel sequence among known targets of DNA-binding proteins. Eleven such GCM-binding sequences are found in the 5' upstream region of the repo gene, whose expression in early glial cells is dependent on gcm. This suggests that the GCM protein is a transcriptional regulator directly controlling repo. We have also identified homologous genes from human and mouse whose products share a highly conserved N-terminal region with Drosophila GCM. At least one of these was shown to have DNA-binding activity similar to that of GCM. By comparing the deduced amino acid sequences of these gene products, we were able to define the "gcm motif," an evolutionarily conserved motif with DNA-binding activity. By PCR amplification, we obtained evidence for the existence of additional gcm-motif genes in mouse as well as in Drosophila. The gcm-motif, therefore, forms a family of novel DNA-binding proteins, and may function in various aspects of cell fate determination.

| S-EPMC26236 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data