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PubMed1998

Removing near-neighbour redundancy from large protein sequence collections.

MOTIVATION: To maximize the chances of biological discovery, homology searching must use an up-to-date collection of sequences. However, the available sequence databases are growing rapidly and are partially redundant in content. This leads to increasing strain on CPU resources and decreasing density of first-hand annotation. RESULTS: These problems are addressed by clustering closely similar sequences to yield a covering of sequence space by a representative subset of sequences. No pair of sequences in the representative set has >90% mutual sequence identity. The representative set is derived by an exhaustive search for close similarities in the sequence database in which the need for explicit sequence alignment is significantly reduced by applying deca- and pentapeptide composition filters. The algorithm was applied to the union of the Swissprot, Swissnew, Trembl, Tremblnew, Genbank, PIR, Wormpep and PDB databases. The all-against-all comparison required to generate a representative set at 90% sequence identity was accomplished in 2 days CPU time, and the removal of fragments and close similarities yielded a size reduction of 46%, from 260 000 unique sequences to 140 000 representative sequences. The practical implications are (i) faster homology searches using, for example, Fasta or Blast, and (ii) unified annotation for all sequences clustered around a representative. As tens of thousands of sequence searches are performed daily world-wide, appropriate use of the non-redundant database can lead to major savings in computer resources, without loss of efficacy. AVAILABILITY: A regularly updated non-redundant protein sequence database (nrdb90), a server for homology searches against nrdb90, and a Perl script (nrdb90.pl) implementing the algorithm are available for academic use from http://www.embl-ebi.ac. uk/holm/nrdb90. CONTACT: holm@embl-ebi.ac.uk

Algorithms↗
PubMed1999

Removing redundancy in SWISS-PROT and TrEMBL.

SUMMARY: One of the distinguishing criteria of the SWISS-PROT protein sequence data bank is minimal redundancy. The introduction of TrEMBL as a supplementary database ensured the comprehensiveness of SWISS-PROT and TrEMBL but introduced some degree of redundancy. We developed a strategy to identify the redundancy present within and between SWISS-PROT and TrEMBL and its subsequent removal. AVAILABILITY: The tools mentioned in this paper are available on request.

Algorithms↗
PubMed2002

Tolerating some redundancy significantly speeds up clustering of large protein databases.

MOTIVATION: Sequence clustering replaces groups of similar sequences in a database with single representatives. Clustering large protein databases like the NCBI Non-Redundant database (NR) using even the best currently available clustering algorithms is very time-consuming and only practical at relatively high sequence identity thresholds. Our previous program, CD-HI, clustered NR at 90% identity in approximately 1 h and at 75% identity in approximately 1 day on a 1 GHz Linux PC (Li et al., Bioinformatics, 17, 282, 2001); however even faster clustering speed is needed because the size of protein databases are rapidly growing and many applications desire a lower attainable thresholds. RESULTS: For our previous algorithm (CD-HI), we have employed short-word filters to speed up the clustering. In this paper, we show that tolerating some redundancy makes for more efficient use of these short-word filters and increases the program's speed 100 times. Our new program implements this technique and clusters NR at 70% identity within 2 h, and at 50% identity in approximately 5 days. Although some redundancy is present after clustering, our new program's results only differ from our previous program's by less than 0.4%.

Algorithms↗
PubMed1997

Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis.

The transcription factor Nur77 (NGFI-B), a member of the steroid nuclear receptor superfamily, is induced to a high level during T-cell receptor (TCR)-mediated apoptosis. A transgenic dominant-negative Nur77 protein can inhibit the apoptotic process accompanying negative selection in thymocytes, while constitutive expression of Nur77 leads to massive cell death. Nur77-deficient mice, however, have no phenotype, suggesting the possible existence of a protein with redundant function to Nur77. To explore this possibility, we have characterized the role of two Nur77 family members, Nurr1 and Nor-1, in TCR-induced apoptosis. We found that Nor-1 and Nurr1 can transactivate through the same DNA element as Nur77, and that their transactivation activities can be blocked by a Nur77 dominant-negative protein. In thymocytes, Nor-1 protein is induced to a very high level upon TCR stimulation and has similar kinetics to Nur77. In contrast, Nurr1 is undetectable in stimulated thymocytes. Furthermore, constitutive expression of Nor-1 in thymocytes leads to massive apoptosis and up-regulation of CD25, suggesting a functional redundancy between Nur77 and Nor-1 gene products. As in the case of our Nur77-FL mice, FasL is not detectable in the thymocytes of Nor-1 transgenic mice. Constitutive expression of Nur77 in gld/gld mice rescues the lymphoproliferative phenotype of the FasL mutant mice. Thus, Nor-1 and Nur77 demonstrate functional redundancy in an apparently Fas-independent apoptosis.

Animals↗
PubMed1984

Ribosomal RNA cistrons of X chromosomes clonally derived from D. melanogaster laboratory populations: redundancy, organization and stability.

To determine whether heterogeneity exists in the organization or redundancy of the rRNA cistrons of inbred populations of Drosophila melanogaster, we have derived a number of sublines from the strains Oregon R and Canton S. These two strains were chosen because our previous studies have demonstrated a difference in the competence of these strains to exhibit a "compensatory response" of the rDNA. In each subline, the X chromosomes are descended from a single maternal X, that is, each line is homozygous for a particular nucleolus organizer (NO). These derivative lines have been characterized in terms of rDNA content and organization, using quantitative liquid hybridizations and Southern blot analyses, respectively. Our studies reveal that both of the highly inbred parent populations contained a heterogeneous array of X chromosomal rDNA contents. Once isogenized, the rDNA redundancy of a given X chromosomal NO can be shown to remain stable for at least 20 generations in culture. We detect no restriction pattern heterogeneity among X chromosomes isolated from a given strain, despite relatively large differences in their rDNA contents. This leads us to suggest that there is no significant clustering of intervening sequence-bearing (ivs+) genes within the rDNA loci of chromosomes from the populations examined. Furthermore, we conclude that apparent alterations in rDNA redundancy known as the compensatory response are not related to the heterogeneity of rDNA content within a population.

Animals↗
PubMed1998

The primary function of a redundant Sp1 binding site in the mouse aprt gene promoter is to block epigenetic gene inactivation.

The promoter region of the mouse adenine phosphoribosyltransferase (aprt) gene contains one non-consensus Sp1 binding site at its 5' end followed by three consensus Sp1 binding sites. The two 3'-most binding sites are sufficient for maximal expression of aprt , suggesting that the non-consensus and consensus binding sites at the 5' end are redundant. However, the two 3' sites are not sufficient to block epigenetic inactivation, which led to the hypothesis that the redundant consensus and/or non-consensus 5' Sp1 binding sites are required to block inactivation events. To test this hypothesis, promoter region constructs were made in which the two 5' Sp1 binding sites were mutated alone or in tandem, and then each construct was tested for its ability to withstand epigenetic inactivation. A cis -acting methylation center that is normally located 1.2 kb upstream of the promoter was used to induce inactivation. The results demonstrate that the presence of the redundant consensus Sp1 binding site is required to block methylation-associated gene inactivation. Therefore, the Sp1 binding sites comprising the mouse aprt promoter have evolved two distinct functions, one to promote transcription and the other to block epigenetic inactivation.

Adenine↗
PubMed1990

Construction of validated, non-redundant composite protein sequence databases.

A strategy has been developed for the construction of a validated, comprehensive composite protein sequence database. Entries are amalgamated from primary source data bases by a largely automated set of processes in which redundant and trivially different entries are eliminated. A modular approach has been adopted to allow scientific judgement to be used at each stage of database processing and amalgamation. Source databases are assigned a priority depending on the quality of sequence validation and commenting. Rejection of entries from the lower priority database, in each pairwise comparison of databases, is carried out according to optionally defined redundancy criteria based on sequence segment mismatches. Efficient algorithms for this methodology are embodied in the COMPO software system. COMPO has been applied for over 2 years in construction and regular updating of the OWL composite protein sequence database from the source databases NBRF-PIR, SWISS-PROT, a GenBank translation retrieved from the feature tables, NBRF-NEW, NEWAT86, PSD-KYOTO and the sequences contained in the Brookhaven protein structure databank. OWL is part of the ISIS integrated data resource of protein sequence and structure [Akrigg et al. (1988) Nature, 335, 745-746]. The modular nature of the integration process greatly facilitates the frequent updating of OWL following releases of the source databases. The extent of redundancy in these sources is revealed by the comparison process. The advantages of a robust composite database for sequence similarity searching and information retrieval are discussed.

Amino Acid Sequence↗
PubMed1982

A redundant ray projection completion method for an inverse fan beam computed tomography system.

An actively synchronized heart gated computed tomography (CT) system has been developed at Peter Bent Brigham Hospital, Boston, MA, for a Technicare 2020 CT scanner. For even the most precise physical synchronization of the scanning apparatus, there will usually be a few gaps in the data for a particular time slice of the cardiac cycle. Of the several gap filling methods that have been developed here, the most nearly ideal is the use of redundant ray measurements. For this type of scanner, there are no truly redundant rays, and normalization errors are particularly problematic. A practical algorithm has been devised and tested here both on phantom data and on cardiac gated data (dog heart). The reconstructions obtained were usually artifact free and showed no loss of resolution, even when up to one-third of the projection data were replaced by redundant ray measurements.

Animals↗
PubMedDate not supplied

Redundancy in a computer-generated order list: meeting the needs of nurses at various levels of practice expertise.

Paper-based clinical practice standards usually pertain to a single diagnosis or clinical condition. When a computerized provider order entry system applies multiple paper-based practice standards to one patient, it generates an order list containing redundant orders. Nurses respond to redundant orders on the basis of their level of nursing expertise with clinical care, computers, and practice standard domains. In this project, orders from three practice standards were manually combined to create a single order list, resulting in 15 duplicate and overlapping orders. A relational database was developed to test the automated removal of redundant orders. As expected, the automatically evaluated order list contained only one of each duplicate order and only the parent of each overlapping order group. Orders were then grouped by related system or function for readability. It is possible to automate the removal of duplicate and overlapping orders from an order list before display to the nurse.

Algorithms↗
PubMed2006

Motion compensation via redundant-wavelet multihypothesis.

Multihypothesis motion compensation has been widely used in video coding with previous attention focused on techniques employing predictions that are diverse spatially or temporally. In this paper, the multihypothesis concept is extended into the transform domain by using a redundant wavelet transform to produce multiple predictions that are diverse in transform phase. The corresponding multiple-phase inverse transform implicitly combines the phase-diverse predictions into a single spatial-domain prediction for motion compensation. The performance advantage of this redundant-wavelet-multihypothesis approach is investigated analytically, invoking the fact that the multiple-phase inverse involves a projection that significantly reduces the power of a dense-motion residual modeled as additive noise. The analysis shows that redundant-wavelet multihypothesis is capable of up to a 7-dB reduction in prediction-residual variance over an equivalent single-phase, single-hypothesis approach. Experimental results substantiate the performance advantage for a block-based implementation.

Algorithms↗
PubMed2004

A unified quadratic-programming-based dynamical system approach to joint torque optimization of physically constrained redundant manipulators.

In this paper, for joint torque optimization of redundant manipulators subject to physical constraints, we show that velocity-level and acceleration-level redundancy-resolution schemes both can be formulated as a quadratic programming (QP) problem subject to equality and inequality/bound constraints. To solve this QP problem online, a primal-dual dynamical system solver is further presented based on linear variational inequalities. Compared to previous researches, the presented QP-solver has simple piecewise-linear dynamics, does not entail real-time matrix inversion, and could also provide joint-acceleration information for manipulator torque control in the velocity-level redundancy-resolution schemes. The proposed QP-based dynamical system approach is simulated based on the PUMA560 robot arm with efficiency and effectiveness demonstrated.

Algorithms↗
PubMed1977

Permissible syndromes. The influence of redundancy on patterns of information.

A model of clinical decision according to Bayes's formula is described and the problem of redundant informations is evaluated. It is postulated that a definitory and a syndromatic redundancy are unavoidable, which is why it is necessary to develop a correction factor. A series of indicants is investigated in two populations, and it is shown that correction for redundancy results in far-reaching changes in the patterns of information. The permissible syndrome is defined: a subset of informations containing the necessary and sufficient predictive capacity. The methods described may be used for an evaluation of common syndromes and may enable comparisons of information patterns, related to identical or different criteria.

Anxiety↗
PubMed2026

A spatiotemporal resolution to genetic redundancy: MIR164 diversification coordinates development and metabolism in Brassica.

Whole-genome duplication (WGD) events create genetic redundancy, posing the evolutionary challenge of how paralogs escape functional overlap to drive innovation. Here, we demonstrate that the MIR164 family in Brassica oleracea resolves this redundancy through spatiotemporal niche partitioning. Following WGD, the family expanded to eight members, which subsequently underwent divergent selection-some preserved under purifying selection, while others showed signals of positive selection. This led to expression divergence, with Bol-MIR164a1 emerging as a key universally expressed paralog. CRISPR-Cas9 mutagenesis of Bol-MIR164a1 revealed its essential role in coordinating two pivotal traits: leaf serration and leaf coloration. Mutants exhibited enhanced leaf serration due to spatial deregulation of CUC2 at organ boundaries, concurrently with yellow-green leaves and elevated flavonoid accumulation. We mechanistically linked the metabolic phenotype to direct transactivation of the anthocyanidin reductase (ANR) promoter by NAC100, alongside its upregulation of chlorophyll catabolism genes. Our findings establish a paradigm in which spatial segregation of target gene expression domains enables a single, widely expressed miRNA paralog to resolve genetic redundancy by independently orchestrating distinct regulatory programs. This provides a fundamental framework for understanding complex trait evolution in polyploids. This allows a single miRNA locus to independently orchestrate both morphological patterning and metabolic programming, providing a fundamental framework for understanding complex trait evolution in polyploid crops.

MicroRNAs↗
PubMedDate not supplied

Cardiac computed tomography using redundant-ray prospective gating.

A fourth-generation, computed tomographic (CT) scanner, equipped for prospectively gated cardiac imaging, was modified to control the scan data acquisition by using knowledge of the location of redundant rays in the sinogram. In conventional prospective gating, a computer monitors the electrocardiogram (ECG) and calculates when to initiate the next scan in a gated series in order to acquire all 360 degrees of projection data for a desired phase of the cardiac cycle. However, in each scan of a series, every projection ray is measured twice (when the positions of the source and detector are reversed). Redundant-ray prospective gating takes advantage of this information to improve the efficiency of data acquisition. Using a heart phantom "beating" at 90 min-1, images of all phases of the cardiac cycle with 100-ms temporal resolution were obtained in four scans with redundant-ray gating; whereas a four-scan series with conventional prospective gating yielded worse images of 170-ms resolution.

Heart↗
PubMed2001

Independent and redundant information in nearby cortical neurons.

In the primary visual cortex (V1), nearby neurons are tuned to similar stimulus features, and, depending on the manner and time scale over which neuronal signals are analyzed, the resulting redundancy may mitigate deleterious effects of response variability. We estimated information rates in the short-time scale responses of clusters of up to six simultaneously recorded nearby neurons in monkey V1. Responses were almost independent if we kept track of which neuron fired each spike but were redundant if we summed responses over the cluster. Redundancy was independent of cluster size. Summing neuronal responses to reduce variability discards potentially useful information, and the discarded information increases with cluster size.

Action Potentials↗
PubMed1963

REDUNDANCY AND BIOLOGICAL AGING.

The relationship between aging and organizational redundancy in biological systems was investigated from the standpoint of information theory. A mortality rate function derived for a randomly deteriorating redundant system approximates observed mortality rates more closely than does the Gompertz function and indicates that variations in redundancy among various mammalian species could account for their widely different rates of aging.

Aging↗
PubMed2006

Limited functional redundancy and oscillation of cyclins in multinucleated Ashbya gossypii fungal cells.

Cyclin protein behavior has not been systematically investigated in multinucleated cells with asynchronous mitoses. Cyclins are canonical oscillating cell cycle proteins, but it is unclear how fluctuating protein gradients can be established in multinucleated cells where nuclei in different stages of the division cycle share the cytoplasm. Previous work in A. gossypii, a filamentous fungus in which nuclei divide asynchronously in a common cytoplasm, demonstrated that one G1 and one B-type cyclin do not fluctuate in abundance across the division cycle. We have undertaken a comprehensive analysis of all G1 and B-type cyclins in A. gossypii to determine whether any of the cyclins show periodic abundance across the cell cycle and to examine whether cyclins exhibit functional redundancy in such a cellular environment. We localized all G1 and B-type cyclins and notably found that only AgClb5/6p varies in subcellular localization during the division cycle. AgClb5/6p is lost from nuclei at the meta-anaphase transition in a D-box-dependent manner. These data demonstrate that efficient nuclear autonomous protein degradation can occur within multinucleated cells residing in a common cytoplasm. We have shown that three of the five cyclins in A. gossypii are essential genes, indicating that there is minimal functional redundancy in this multinucleated system. In addition, we have identified a cyclin, AgClb3/4p, that is essential only for sporulation. We propose that the cohabitation of different cyclins in nuclei has led to enhanced substrate specificity and limited functional redundancy within classes of cyclins in multinucleated cells.

Active Transport, Cell Nucleus↗
PubMed2000

Fission yeast homologs of human CENP-B have redundant functions affecting cell growth and chromosome segregation.

Two functionally important DNA sequence elements in centromeres of the fission yeast Schizosaccharomyces pombe are the centromeric central core and the K-type repeat. Both of these DNA elements show internal functional redundancy that is not correlated with a conserved DNA sequence. Specific, but degenerate, sequences in these elements are bound in vitro by the S. pombe DNA-binding proteins Abp1p (also called Cbp1p) and Cbhp, which are related to the mammalian centromere DNA-binding protein CENP-B. In this study, we determined that Abp1p binds to at least one of its target sequences within S. pombe centromere II central core (cc2) DNA with an affinity (K(s) = 7 x 10(9) M(-1)) higher than those of other known centromere DNA-binding proteins for their cognate targets. In vivo, epitope-tagged Cbhp associated with centromeric K repeat chromatin, as well as with noncentromeric regions. Like abp1(+)/cbp1(+), we found that cbh(+) is not essential in fission yeast, but a strain carrying deletions of both genes (Deltaabp1 Deltacbh) is extremely compromised in growth rate and morphology and missegregates chromosomes at very high frequency. The synergism between the two null mutations suggests that these proteins perform redundant functions in S. pombe chromosome segregation. In vitro assays with cell extracts with these proteins depleted allowed the specific assignments of several binding sites for them within cc2 and the K-type repeat. Redundancy observed at the centromere DNA level appears to be reflected at the protein level, as no single member of the CENP-B-related protein family is essential for proper chromosome segregation in fission yeast. The relevance of these findings to mammalian centromeres is discussed.

Autoantigens↗