The sufficient minimal set of miRNA seed types.
Ontology highlight
ABSTRACT: Motivation
Pairing between the target sequence and the 6-8 nt long seed sequence of the miRNA presents the most important feature for miRNA target site prediction. Novel high-throughput technologies such as Argonaute HITS-CLIP afford meanwhile a detailed study of miRNA:mRNA duplices. These interaction maps enable a first discrimination between functional and non-functional target sites in a bulky fashion. Prediction algorithms apply different seed paradigms to identify miRNA target sites. Therefore, a quantitative assessment of miRNA target site prediction is of major interest.Results
We identified a set of canonical seed types based on a transcriptome wide analysis of experimentally verified functional target sites. We confirmed the specificity of long seeds but we found that the majority of functional target sites are formed by less specific seeds of only 6 nt indicating a crucial role of this type. A substantial fraction of genuine target sites arenon-conserved. Moreover, the majority of functional sites remain uncovered by common prediction methods.
SUBMITTER: Ellwanger DC
PROVIDER: S-EPMC3087955 | biostudies-literature | 2011 May
REPOSITORIES: biostudies-literature
Publications
The sufficient minimal set of miRNA seed types.
Ellwanger Daniel C DC Büttner Florian A FA Mewes Hans-Werner HW Stümpflen Volker V
Bioinformatics (Oxford, England) 20110326 10
<h4>Motivation</h4>Pairing between the target sequence and the 6-8 nt long seed sequence of the miRNA presents the most important feature for miRNA target site prediction. Novel high-throughput technologies such as Argonaute HITS-CLIP afford meanwhile a detailed study of miRNA:mRNA duplices. These interaction maps enable a first discrimination between functional and non-functional target sites in a bulky fashion. Prediction algorithms apply different seed paradigms to identify miRNA target sites ...[more]
Similar Datasets
Project description:Identifying tumor-specific T cell clones that mediate immunotherapy responses remains challenging. Mutation-associated neoantigen (MANA) -specific CD8+ tumor-infiltrating lymphocytes (TIL) have been shown to express high levels of CXCL13 and CD39 (ENTPD1), and low IL-7 receptor (IL7R) levels in many cancer types, but their collective relevance to T cell functionality has not been established. Here we present an integrative tool to identify MANA-specific TIL using weighted expression levels of these three genes in lung cancer and melanoma single-cell RNAseq datasets. Our three-gene "MANAscore" algorithm outperforms other RNAseq-based algorithms in identifying validated neoantigen-specific CD8+ clones, and accurately identifies TILs that recognize other classes of tumor antigens, including cancer testis antigens, endogenous retroviruses and viral oncogenes. Most of these TIL are characterized by a tissue resident memory gene expression program. Putative tumor-reactive cells (pTRC) identified via MANAscore in anti-PD-1-treated lung tumors had higher expression of checkpoint and cytotoxicity-related genes relative to putative non-tumor-reactive cells. pTRC in pathologically responding tumors showed distinguished gene expression patterns and trajectories. Collectively, we show that MANAscore is a robust tool that can greatly enrich candidate tumor-specific T cells and be used to understand the functional programming of tumor-reactive TIL.
| S-EPMC11791090 | biostudies-literature
Project description:BackgroundGene set analysis (GSA) aims to evaluate the association between the expression of biological pathways, or a priori defined gene sets, and a particular phenotype. Numerous GSA methods have been proposed to assess the enrichment of sets of genes. However, most methods are developed with respect to a specific alternative scenario, such as a differential mean pattern or a differential coexpression. Moreover, a very limited number of methods can handle either binary, categorical, or continuous phenotypes. In this paper, we develop two novel GSA tests, called SDRs, based on the sufficient dimension reduction technique, which aims to capture sufficient information about the relationship between genes and the phenotype. The advantages of our proposed methods are that they allow for categorical and continuous phenotypes, and they are also able to identify a variety of enriched gene sets.ResultsThrough simulation studies, we compared the type I error and power of SDRs with existing GSA methods for binary, triple, and continuous phenotypes. We found that SDR methods adequately control the type I error rate at the pre-specified nominal level, and they have a satisfactory power to detect gene sets with differential coexpression and to test non-linear associations between gene sets and a continuous phenotype. In addition, the SDR methods were compared with seven widely-used GSA methods using two real microarray datasets for illustration.ConclusionsWe concluded that the SDR methods outperform the others because of their flexibility with regard to handling different kinds of phenotypes and their power to detect a wide range of alternative scenarios. Our real data analysis highlights the differences between GSA methods for detecting enriched gene sets.
| S-EPMC4744442 | biostudies-literature
Project description:BackgroundCircadian clocks are found in organisms of almost all domains including photosynthetic Cyanobacteria, whereby large diversity exists within the protein components involved. In the model cyanobacterium Synechococcus elongatus PCC 7942 circadian rhythms are driven by a unique KaiABC protein clock, which is embedded in a network of input and output factors. Homologous proteins to the KaiABC clock have been observed in Bacteria and Archaea, where evidence for circadian behavior in these domains is accumulating. However, interaction and function of non-cyanobacterial Kai-proteins as well as homologous input and output components remain mainly unclear.ResultsUsing a universal BLAST analyses, we identified putative KaiC-based timing systems in organisms outside as well as variations within Cyanobacteria. A systematic analyses of publicly available microarray data elucidated interesting variations in circadian gene expression between different cyanobacterial strains, which might be correlated to the diversity of genome encoded clock components. Based on statistical analyses of co-occurrences of the clock components homologous to Synechococcus elongatus PCC 7942, we propose putative networks of reduced and fully functional clock systems. Further, we studied KaiC sequence conservation to determine functionally important regions of diverged KaiC homologs. Biochemical characterization of exemplary cyanobacterial KaiC proteins as well as homologs from two thermophilic Archaea demonstrated that kinase activity is always present. However, a KaiA-mediated phosphorylation is only detectable in KaiC1 orthologs.ConclusionOur analysis of 11,264 genomes clearly demonstrates that components of the Synechococcus elongatus PCC 7942 circadian clock are present in Bacteria and Archaea. However, all components are less abundant in other organisms than Cyanobacteria and KaiA, Pex, LdpA, and CdpA are only present in the latter. Thus, only reduced KaiBC-based or even simpler, solely KaiC-based timing systems might exist outside of the cyanobacterial phylum, which might be capable of driving diurnal oscillations.
| S-EPMC5520375 | biostudies-literature
Project description:We have investigated the title question for the W4-08 thermochemical benchmark using l-saturated truncations of a large reference (REF) basis set, as well as for standard F12-optimized basis sets. With the REF basis set, the root-mean-square (RMS) contribution of i functions to the MP2-F12 total atomization energies (TAEs) is about 0.01 kcal/mol, the largest individual contributions being 0.04 kcal/mol for P2 and P4. However, even for these cases, basis set extrapolation from {g,h} basis sets adequately addresses the problem. Using basis sets insufficiently saturated in the spdfgh angular momenta may lead to exaggerated i function contributions. For extrapolation from spdfg and spdfgh basis sets, basis set convergence appears to be quite close to the theoretical asymptotic ∝ L-7 behavior. We hence conclude that h functions are sufficient even for highly demanding F12 applications. With one-parameter extrapolation, spdf and spdfg basis sets are adequate, aug-cc-pV{T,Q}Z-F12 yielding a RMSD = 0.03 kcal/mol. A limited exploration of CCSD(F12*) and CCSD-F12b suggests our conclusions are applicable to higher-level F12 methods as well.
| S-EPMC9234959 | biostudies-literature
Project description:Thermus thermophilus is a thermophilic model organism distantly related to the mesophilic model organism E. coli. We reconstituted protein translation of Thermus thermophilus in vitro from purified ribosomes, transfer ribonucleic acids (tRNAs) and 33 recombinant proteins. This reconstituted system was fully functional, capable of translating natural messenger RNA (mRNA) into active full-length proteins at temperatures up to 65°C and with yields up to 60 μg/ml. Surprisingly, the synthesis of active proteins also occurred at 37°C, a temperature well below the minimal growth temperature for T. thermophilus. A polyamine was required, with tetraamine being most effective, for translation at both high and low temperatures. Using such a defined in vitro system, we demonstrated a minimal set of components that are sufficient for synthesizing active proteins at high temperatures, the functional compatibility of key translation components between T. thermophilus and E. coli, and the functional conservation of a number of resurrected ancient elongation factors. This work sets the stage for future experiments that apply abundant structural information to biochemical characterization of protein translation and folding in T. thermophilus. Because it contains significantly reduced nucleases and proteases, this reconstituted thermostable cell-free protein synthesis system may enable in vitro engineering of proteins with improved thermostability.
| S-EPMC3439929 | biostudies-literature
Project description:MicroRNAs (miRNAs) are short noncoding RNAs that are involved in post-transcriptional regulation of mRNAs. Microarrays have been employed to measure global miRNA expressions; however, because the number of miRNAs is much smaller than the number of mRNAs, it is not clear whether traditional normalization methods developed for mRNA arrays are suitable for miRNA. This is an important question, since normalization affects downstream analyses of the data. In this paper we develop a least-variant set (LVS) normalization method, which was previously shown to outperform other methods in mRNA analysis when standard assumptions are violated. The selection of the LVS miRNAs is based on a robust linear model fit of the probe-level data that takes into account the considerable differences in variances between probes. In a spike-in study, we show that the LVS has similar operating characteristics, in terms of sensitivity and specificity, compared with the ideal normalization, and it is better than no normalization, 75th percentile-shift, quantile, global median, VSN, and lowess normalization methods. We evaluate four expression-summary measures using a tissue data set; summarization from the robust model performs as well as the others. Finally, comparisons using expression data from two dissimilar tissues and two similar ones show that LVS normalization has better operating characteristics than other normalizations.
| S-EPMC2995391 | biostudies-literature
Project description:The availability of a large number of complete genome sequences raises the question of how many genes are essential for cellular life. Trying to reconstruct the core of the protein-coding gene set for a hypothetical minimal bacterial cell, we have performed a computational comparative analysis of eight bacterial genomes. Six of the analyzed genomes are very small due to a dramatic genome size reduction process, while the other two, corresponding to free-living relatives, are larger. The available data from several systematic experimental approaches to define all the essential genes in some completely sequenced bacterial genomes were also considered, and a reconstruction of a minimal metabolic machinery necessary to sustain life was carried out. The proposed minimal genome contains 206 protein-coding genes with all the genetic information necessary for self-maintenance and reproduction in the presence of a full complement of essential nutrients and in the absence of environmental stress. The main features of such a minimal gene set, as well as the metabolic functions that must be present in the hypothetical minimal cell, are discussed.
| S-EPMC515251 | biostudies-literature
Project description:Bioconjugate vaccines, consisting of polysaccharides attached to carrier proteins, are enzymatically generated using prokaryotic glycosylation systems in a process termed bioconjugation. Key to bioconjugation are a group of enzymes known as oligosaccharyltransferases (OTases) that transfer polysaccharides to engineered carrier proteins containing conserved amino acid sequences known as sequons. The most recently discovered OTase, PglS, has been shown to have the broadest substrate scope, transferring many different types of bacterial glycans including those with glucose at the reducing end. However, PglS is currently the least understood in terms of the sequon it recognizes. PglS is a pilin-specific O-linking OTase that naturally glycosylates a single protein, ComP. In addition to ComP, we previously demonstrated that an engineered carrier protein containing a large fragment of ComP is also glycosylated by PglS. Here we sought to identify the minimal ComP sequon sufficient for PglS glycosylation. We tested >100 different ComP fragments individually fused to Pseudomonas aeruginosa exotoxin A (EPA), leading to the identification of an 11-amino acid sequence sufficient for robust glycosylation by PglS. We also demonstrate that the placement of the ComP sequon on the carrier protein is critical for stability and subsequent glycosylation. Moreover, we identify novel sites on the surface of EPA that are amenable to ComP sequon insertion and find that Cross-Reactive Material 197 fused to a ComP fragment is also glycosylated. These results represent a significant expansion of the glycoengineering toolbox as well as our understanding of bacterial O-linking sequons.
| S-EPMC8457361 | biostudies-literature
Project description:BackgroundGrapevine reproductive development has direct implications on yield. It also impacts on berry and wine quality by affecting traits like seedlessness, berry and bunch size, cluster compactness and berry skin to pulp ratio. Seasonal fluctuations in yield, fruit composition and wine attributes, which are largely driven by climatic factors, are major challenges for worldwide table grape and wine industry. Accordingly, a better understanding of reproductive processes such as gamete development, fertilization, seed and fruit set is of paramount relevance for managing yield and quality. With the aim of providing new insights into this field, we searched for clones with contrasting seed content in two germplasm collections.ResultsWe identified eight variant pairs that seemingly differ only in seed-related characteristics while showing identical genotype when tested with the GrapeReSeq_Illumina_20K_SNP_chip and several microsatellites. We performed multi-year observations on seed and fruit set deriving from different pollination treatments, with special emphasis on the pair composed by Sangiovese and its seedless variant locally named Corinto Nero. The pollen of Corinto Nero failed to germinate in vitro and gave poor berry set when used to pollinate other varieties. Most berries from both open- and cross-pollinated Corinto Nero inflorescences did not contain seeds. The genetic analysis of seedlings derived from occasional Corinto Nero normal seeds revealed that the few Corinto Nero functional gametes are mostly unreduced. Moreover, three genotypes, including Sangiovese and Corinto Nero, were unexpectedly found to develop fruits without pollen contribution and occasionally showed normal-like seeds. Five missense single nucleotide polymorphisms were identified between Corinto Nero and Sangiovese from transcriptomic data.ConclusionsOur observations allowed us to attribute a seedlessness type to some variants for which it was not documented in the literature. Interestingly, the VvAGL11 mutation responsible for Sultanina stenospermocarpy was also discovered in a seedless mutant of Gouais Blanc. We suggest that Corinto Nero parthenocarpy is driven by pollen and/or embryo sac defects, and both events likely arise from meiotic anomalies. The single nucleotide polymorphisms identified between Sangiovese and Corinto Nero are suitable for testing as traceability markers for propagated material and as functional candidates for the seedless phenotype.
| S-EPMC7955655 | biostudies-literature
Project description:In the "personalized medicine" era, one of the most difficult problems is identification of combined markers from different omics platforms. Many methods have been developed to identify candidate markers for each type of omics data, but few methods facilitate the identification of multiple markers on multi-omics platforms. microRNAs (miRNAs) is well known to affect only indirectly phenotypes by regulating mRNA expression and/or protein translation. To take into account this knowledge into practice, we suggest a miRNA-mRNA integration model for survival time analysis, called mimi-surv, which accounts for the biological relationship, to identify such integrated markers more efficiently. Through simulation studies, we found that the statistical power of mimi-surv be better than other models. Application to real datasets from Seoul National University Hospital and The Cancer Genome Atlas demonstrated that mimi-surv successfully identified miRNA-mRNA integrations sets associated with progression-free survival of pancreatic ductal adenocarcinoma (PDAC) patients. Only mimi-surv found miR-96, a previously unidentified PDAC-related miRNA in these two real datasets. Furthermore, mimi-surv was shown to identify more PDAC related miRNAs than other methods because it used the known structure for miRNA-mRNA regularization. An implementation of mimi-surv is available at http://statgen.snu.ac.kr/software/mimi-surv.
| S-EPMC8276759 | biostudies-literature