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Results for “Molecular Sequence Annotation”

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PubMed2006

SAGE2Splice: unmapped SAGE tags reveal novel splice junctions.

Serial analysis of gene expression (SAGE) not only is a method for profiling the global expression of genes, but also offers the opportunity for the discovery of novel transcripts. SAGE tags are mapped to known transcripts to determine the gene of origin. Tags that map neither to a known transcript nor to the genome were hypothesized to span a splice junction, for which the exon combination or exon(s) are unknown. To test this hypothesis, we have developed an algorithm, SAGE2Splice, to efficiently map SAGE tags to potential splice junctions in a genome. The algorithm consists of three search levels. A scoring scheme was designed based on position weight matrices to assess the quality of candidates. Using optimized parameters for SAGE2Splice analysis and two sets of SAGE data, candidate junctions were discovered for 5%-6% of unmapped tags. Candidates were classified into three categories, reflecting the previous annotations of the putative splice junctions. Analysis of predicted tags extracted from EST sequences demonstrated that candidate junctions having the splice junction located closer to the center of the tags are more reliable. Nine of these 12 candidates were validated by RT-PCR and sequencing, and among these, four revealed previously uncharacterized exons. Thus, SAGE2Splice provides a new functionality for the identification of novel transcripts and exons. SAGE2Splice is available online at http://www.cisreg.ca.

Algorithms↗

PubMed2005

The putative lipase, AF1763, from Archaeoglobus fulgidusis is a carboxylesterase with a very high pH optimum.

The open reading frame AF1763, annotated as a putative lipase gene (lipA) of the hyperthermophilic archaeon, Archaeoglobus fulgidus DSM 4304, was cloned and over-expressed in E. coli. A sequence analysis of LipA and the investigation of a truncated enzyme implied a special function of the C-terminal part of LipA. The substrate spectrum of the enzyme suggested that LipA is a carboxylesterase rather than a canonical lipase. The enzyme showed optimal activity at 70 degrees C and between pH 10 and 11, which is among the most alkaline pH range detected for hydrolases.

Archaeal Proteins↗

PubMed2001

A database and tools for 3-D protein structure comparison and alignment using the Combinatorial Extension (CE) algorithm.

The database reported here is derived using the Combinatorial Extension (CE) algorithm which compares pairs of protein polypeptide chains and provides a list of structurally similar proteins along with their structure alignments. Using CE, structure-structure alignments can provide insights into biological function. When a protein of known function is shown to be structurally similar to a protein of unknown function, a relationship might be inferred; a relationship not necessarily detectable from sequence comparison alone. Establishing structure-structure relationships in this way is of great importance as we enter an era of structural genomics where there is a likelihood of an increasing number of structures with unknown functions being determined. Thus the CE database is an example of a useful tool in the annotation of protein structures of unknown function. Comparisons can be performed on the complete PDB or on a structurally representative subset of proteins. The source protein(s) can be from the PDB (updated monthly) or uploaded by the user. CE provides sequence alignments resulting from structural alignments and Cartesian coordinates for the aligned structures, which may be analyzed using the supplied Compare3D Java applet, or downloaded for further local analysis. Searches can be run from the CE web site, http://cl.sdsc.edu/ce.html, or the database and software downloaded from the site for local use.

Algorithms↗

PubMed2001

Structure of the YSPTSPS repeat containing two SPXX motifs in the CTD of RNA polymerase II: NMR studies of cyclic model peptides reveal that the SPTS turn is more stable than SPSY in water.

The carboxyl-terminal domain of RNA polymerase II, which is rich in phosphorylation sites, contains 17--52 tandem repeats with the consensus sequence of the heptapeptide, YSPTSPS. The repeat unit of the heptapeptide has two SPXX motifs showing potential beta-turns, SPTS and SPSY. NMR studies were performed in water at pH 4.0 for two cyclic peptides containing one and two repeat units, cyclo-[C(1)R(2)D(3)Y(4)S(5)P(6)T(7)S(8)P(9)S(10)Y(11)S(12)R(13)D(14)C(15)] (peptide 1) and cyclo-[C(1)R(2)D(3)Y(4)S(5)P(6)T(7)S(8)P(9)S(10)Y(11)S(12)P(13)T(14)S(15)P(16)N(17)Y(18)S(19)R(20)D(21)C(22)] (peptide 2), which are cyclized with a disulfide bridge of two Cys residues at the N- and C-termini. SP in 1 and 2 are predominantly in trans form. The following NMR parameters were detected: (1) lower temperature coefficients of amide proton chemical shifts of T7 and S8 in 1, and Tx (T7 or T14), Sx (S8 or S15), Tz (T14 or T7) and Sz (S15 or S8) in 2, (2) significantly large deviation of H(alpha) chemical shifts from its random coil value (Delta H(alpha)) of Pro preceding the Thr (P6 in 1, and Px and Pz in 2), (3) relatively large (3)J(HNH alpha) coupling constants (>8.7 Hz) of T7 in 1 and Tx and Tz in 2, and (4) NOE (d(NN) (i, i+1)) connectivities between the amide protons of T7-S8 and S10-Y11 in 1, and Tx-Sx, S10-Y11, Tz-Sz, and N17-Y18 in 2, although two Pro-Thr-Ser segments in 2 (each of these are annotated by 'x' and 'z') in the first and second repeat units were not distinguishable. Comparison of the NMR parameters between the cyclic peptides and the corresponding linear peptides indicates that cyclization promotes structural stabilization in water. The present NMR data were consistent with the presence of a beta-turn at both SPTS and SPSY: S(5)P(6)T(7)S(8) and S(8)P(9)S(10)Y(11) in 1, and SPxTxSx, SPzTzSz, SP(9)S(10)Y(11), SP(16)N(17)Y(18) in 2. However, the structure of the SPTS segment is more stable than that of the SPSY segment. Conformations consistent with NMR parameters including NOE distances were obtained through molecular dynamics and energy minimization methods. These calculations yielded two stable conformers for the SPTS segment. One of the two corresponds to a type I beta-turn.

Amino Acid Sequence↗

PubMed2001

Analysis of the chromosome sequence of the legume symbiont Sinorhizobium meliloti strain 1021.

Sinorhizobium meliloti is an alpha-proteobacterium that forms agronomically important N(2)-fixing root nodules in legumes. We report here the complete sequence of the largest constituent of its genome, a 62.7% GC-rich 3,654,135-bp circular chromosome. Annotation allowed assignment of a function to 59% of the 3,341 predicted protein-coding ORFs, the rest exhibiting partial, weak, or no similarity with any known sequence. Unexpectedly, the level of reiteration within this replicon is low, with only two genes duplicated with more than 90% nucleotide sequence identity, transposon elements accounting for 2.2% of the sequence, and a few hundred short repeated palindromic motifs (RIME1, RIME2, and C) widespread over the chromosome. Three regions with a significantly lower GC content are most likely of external origin. Detailed annotation revealed that this replicon contains all housekeeping genes except two essential genes that are located on pSymB. Amino acid/peptide transport and degradation and sugar metabolism appear as two major features of the S. meliloti chromosome. The presence in this replicon of a large number of nucleotide cyclases with a peculiar structure, as well as of genes homologous to virulence determinants of animal and plant pathogens, opens perspectives in the study of this bacterium both as a free-living soil microorganism and as a plant symbiont.

Bacterial Proteins↗

PubMed2001

GlycoMod--a software tool for determining glycosylation compositions from mass spectrometric data.

GlycoMod (http://www.expasy.ch/tools/glycomod/) is a software tool designed to find all possible compositions of a glycan structure from its experimentally determined mass. The program can be used to predict the composition of any glycoprotein-derived oligosaccharide comprised of either underivatised, methylated or acetylated monosaccharides, or with a derivatised reducing terminus. The composition of a glycan attached to a peptide can be computed if the sequence or mass of the peptide is known. In addition, if the protein is known and is contained in the SWISS-PROT or TrEMBL databases, the program will match the experimentally determined masses against all the predicted protease-produced peptides (including any post-translational modifications annotated in these databases) which have the potential to be glycosylated with either N- or O-linked oligosaccharides. Since many possible glycan compositions can be generated from the same mass, the program can apply compositional constraints to the output if the user supplies either known or suspected monosaccharide constituents. Furthermore, known oligosaccharide structural constraints on monosaccharide composition are also incorporated into the program to limit the output.

Carbohydrate Sequence↗

PubMed2006

Differential label-free quantitative proteomic analysis of Shewanella oneidensis cultured under aerobic and suboxic conditions by accurate mass and time tag approach.

We describe the application of LC-MS without the use of stable isotope labeling for differential quantitative proteomic analysis of whole cell lysates of Shewanella oneidensis MR-1 cultured under aerobic and suboxic conditions. LC-MS/MS was used to initially identify peptide sequences, and LC-FTICR was used to confirm these identifications as well as measure relative peptide abundances. 2343 peptides covering 668 proteins were identified with high confidence and quantified. Among these proteins, a subset of 56 changed significantly using statistical approaches such as statistical analysis of microarrays, whereas another subset of 56 that were annotated as performing housekeeping functions remained essentially unchanged in relative abundance. Numerous proteins involved in anaerobic energy metabolism exhibited up to a 10-fold increase in relative abundance when S. oneidensis was transitioned from aerobic to suboxic conditions.

Amino Acid Sequence↗

PubMed2003

The PlantsP and PlantsT Functional Genomics Databases.

PlantsP and PlantsT allow users to quickly gain a global understanding of plant phosphoproteins and plant membrane transporters, respectively, from evolutionary relationships to biochemical function as well as a deep understanding of the molecular biology of individual genes and their products. As one database with two functionally different web interfaces, PlantsP and PlantsT are curated plant-specific databases that combine sequence-derived information with experimental functional-genomics data. PlantsP focuses on proteins involved in the phosphorylation process (i.e., kinases and phosphatases), whereas PlantsT focuses on membrane transport proteins. Experimentally, PlantsP provides a resource for information on a collection of T-DNA insertion mutants (knockouts) in each kinase and phosphatase, primarily in Arabidopsis thaliana, and PlantsT uniquely combines experimental data regarding mineral composition (derived from inductively coupled plasma atomic emission spectroscopy) of mutant and wild-type strains. Both databases provide extensive information on motifs and domains, detailed information contributed by individual experts in their respective fields, and descriptive information drawn directly from the literature. The databases incorporate a unique user annotation and review feature aimed at acquiring expert annotation directly from the plant biology community. PlantsP is available at http://plantsp.sdsc.edu and PlantsT is available at http://plantst.sdsc.edu.

Arabidopsis↗

PubMed2003

FIE2: A program for the extraction of genomic DNA sequences around the start and translation initiation site of human genes.

FIE2 (5' end Information Extraction v2) is a web-based program for easy identification and extraction of nucleotide sequence around the start of genes (promoter region) and their translation initiation site (TIS). Using information provided by the National Center for Biotechnology Information's (NCBI's) LocusLink, FIE2 identifies the 5'-most end of a gene on its respective chromosome based on alignment of a selected set of mRNAs representative of the gene. FIE2 then uses currently available human genome sequence information to extract the desired sequences. The accuracy of the information extracted is therefore limited by the accuracy and completeness of the sequence annotation and sequence alignment provided by LocusLink. In addition, multiple TIS positions are also occasionally presented, for example, as a result of multiple alignments of transcript variants. One of the key criteria of FIE2 is that it should extract only the correct information or attempt no extraction at all. To date, the authors are not aware of any publicly available web-based tool that uses the human genomic sequence to extract pertinent promoter- and TIS-region information in this fashion. FIE2 is freely available at http://sdmc.lit.org.sg/FIE2.0.

Base Sequence↗

PubMed2004

JASPAR: an open-access database for eukaryotic transcription factor binding profiles.

The analysis of regulatory regions in genome sequences is strongly based on the detection of potential transcription factor binding sites. The preferred models for representation of transcription factor binding specificity have been termed position-specific scoring matrices. JASPAR is an open-access database of annotated, high-quality, matrix-based transcription factor binding site profiles for multicellular eukaryotes. The profiles were derived exclusively from sets of nucleotide sequences experimentally demonstrated to bind transcription factors. The database is complemented by a web interface for browsing, searching and subset selection, an online sequence analysis utility and a suite of programming tools for genome-wide and comparative genomic analysis of regulatory regions. JASPAR is available at http://jaspar. cgb.ki.se.

Animals↗

PubMed2006

pSTIING: a 'systems' approach towards integrating signalling pathways, interaction and transcriptional regulatory networks in inflammation and cancer.

pSTIING (http://pstiing.licr.org) is a new publicly accessible web-based application and knowledgebase featuring 65 228 distinct molecular associations (comprising protein-protein, protein-lipid, protein-small molecule interactions and transcriptional regulatory associations), ligand-receptor-cell type information and signal transduction modules. It has a particular major focus on regulatory networks relevant to chronic inflammation, cell migration and cancer. The web application and interface provide graphical representations of networks allowing users to combine and extend transcriptional regulatory and signalling modules, infer molecular interactions across species and explore networks via protein domains/motifs, gene ontology annotations and human diseases. pSTIING also supports the direct cross-correlation of experimental results with interaction information in the knowledgebase via the CLADIST tool associated with pSTIING, which currently analyses and clusters gene expression, proteomic and phenotypic datasets. This allows the contextual projection of co-expression patterns onto prior network information, facilitating the identification of functional modules in physiologically relevant systems.

Amino Acid Motifs↗

PubMed2005

Global gene annotation analysis and transcriptional profiling identify key biological modules in hypoxic pulmonary hypertension.

Chronic hypoxic pulmonary hypertension is an important clinical disorder causing significant morbidity. Despite recent discoveries, many molecular mechanisms involved in its pathogenesis remain unexplored. We have undertaken a systematic and unbiased approach to gain global insights into this complex process. By combining transcriptional profiling with rigorous statistical methods and cluster analysis, we identified the dominant temporal patterns of gene expression during progression and regression of hypoxic pulmonary hypertension. We next integrated these results with global gene annotation analysis to identify key biological themes involved in the development and resolution of hypoxic pulmonary hypertension and vascular remodeling. This novel approach assigned biological roles to thousands of candidate genes based on their temporal expression profiles and membership in specific biological modules. Our procedure confirmed several molecular pathways and gene products known to be important in hypoxic pulmonary hypertension. Furthermore, we discovered several novel candidates and molecular mechanisms, including IQ motif containing GTPase-activating protein-1 (IQGAP1), decorin, insulin-like growth factor binding protein-3 (IGFBP3), and lactotransferrin, that may play crucial roles in hypoxic pulmonary hypertension and vascular remodeling. Our methodology of integrating transcriptional profiling, cluster analysis, and global gene annotation provides new insights into the pathophysiology of pulmonary hypertension and is applicable to other models of human disease.

Animals↗

PubMed2006

Sequence analysis of the porcine IFNAR1 and IFNGR2 genes.

A porcine BAC clone harboring the tightly linked IFNAR1 and IFNGR2 genes was identified by comparative analysis of the publicly available porcine BAC end sequences. The complete 168,835 bp insert sequence of this clone was determined. Sequence comparisons of the genomic sequence with EST sequences from public databases were performed and allowed a detailed annotation of the IFNAR1 and IFNGR2 genes. The analyzed genes showed a conserved genomic organization with their known mammalian orthologs, however the sequence conservation of these genes across species was relatively low. In addition to the IFNAR1 and IFNGR2 genes, which were completely sequenced, the analyzed BAC clone also contained parts of an orphan gene encoding a putative transmembrane protein (TMEM50B). In contrast to the IFNAR1 and IFNGR2 genes the sequence conservation of the TMEM50B gene across different mammalian species was extremely high.

Amino Acid Sequence↗

PubMed2005

Development of ESTs from chickpea roots and their use in diversity analysis of the Cicer genus.

BACKGROUND: Chickpea is a major crop in many drier regions of the world where it is an important protein-rich food and an increasingly valuable traded commodity. The wild annual Cicer species are known to possess unique sources of resistance to pests and diseases, and tolerance to environmental stresses. However, there has been limited utilization of these wild species by chickpea breeding programs due to interspecific crossing barriers and deleterious linkage drag. Molecular genetic diversity analysis may help predict which accessions are most likely to produce fertile progeny when crossed with chickpea cultivars. While, trait-markers may provide an effective tool for breaking linkage drag. Although SSR markers are the assay of choice for marker-assisted selection of specific traits in conventional breeding populations, they may not provide reliable estimates of interspecific diversity, and may lose selective power in backcross programs based on interspecific introgressions. Thus, we have pursued the development of gene-based markers to resolve these problems and to provide candidate gene markers for QTL mapping of important agronomic traits. RESULTS: An EST library was constructed after subtractive suppressive hybridization (SSH) of root tissue from two very closely related chickpea genotypes (Cicer arietinum). A total of 106 EST-based markers were designed from 477 sequences with functional annotations and these were tested on C. arietinum. Forty-four EST markers were polymorphic when screened across nine Cicer species (including the cultigen). Parsimony and PCoA analysis of the resultant EST-marker dataset indicated that most accessions cluster in accordance with the previously defined classification of primary (C. arietinum, C. echinospermum and C. reticulatum), secondary (C. pinnatifidum, C. bijugum and C. judaicum), and tertiary (C. yamashitae, C. chrossanicum and C. cuneatum) gene-pools. A large proportion of EST alleles (45%) were only present in one or two of the accessions tested whilst the others were represented in up to twelve of the accessions tested. CONCLUSION: Gene-based markers have proven to be effective tools for diversity analysis in Cicer and EST diversity analysis may be useful in identifying promising candidates for interspecific hybridization programs. The EST markers generated in this study have detected high levels of polymorphism amongst both common and rare alleles. This suggests that they would be useful for allele-mining of germplasm collections for identification of candidate accessions in the search for new sources of resistance to pests / diseases, and tolerance to abiotic stresses.

Biomarkers↗

PubMed2006

A sodium bicarbonate transporter from sea urchin spermatozoa.

Bicarbonate (HCO3-) transporters play crucial roles in cell-signaling pathways and are essential for cell viability. Here we describe the first cloning and localization of a HCO3- transporter from sperm of the sea urchin, Strongylocentrotus purpuratus. The deduced protein is 1214 amino acids and has a calculated molecular mass of 135 kDa. The annotated protein coding region of the transporter gene consists of 24 exons. The most similar human protein is the Na+/HCO3- cotransporter-2 (NBC2), which has 53% identity and 68% similarity to the sea urchin protein. The sea urchin protein shares the major structural features of HCO3- transporters, including 13 transmembrane segments, a DIDS (4,4-diiodothiocyanatostilbene-2, 2-disulfonic acid) binding motif and N-linked glycosylation sites. It has longer N- and C-terminal cytoplasmic domains compared to human HCO3- transporters. The sea urchin protein possesses a relatively long 3rd extracellular loop with four conserved cysteine residues. This is characteristic for Na+/HCO3- cotransporters, but not for anion exchangers, suggesting that the sea urchin protein is a Na+/HCO3- cotransporter. It is therefore designated as Sp-NBC. A neighbor-joining tree shows that Sp-NBC branches closer to the electroneutral type of HCO3- transporters. Western immunoblots and immunoflourescence show that Sp-NBC is concentrated in the flagellar plasma membrane, suggesting a role in motility regulation.

Amino Acid Sequence↗

PubMed2006

EVEREST: a collection of evolutionary conserved protein domains.

Protein domains are subunits of proteins that recur throughout the protein world. There are many definitions attempting to capture the essence of a protein domain, and several systems that identify protein domains and classify them into families. EVEREST, recently described in Portugaly et al. (2006) BMC Bioinformatics, 7, 277, is one such system that performs the task automatically, using protein sequence alone. Herein we describe EVEREST release 2.0, consisting of 20,029 families, each defined by one or more HMMs. The current EVEREST database was constructed by scanning UniProt 8.1 and all PDB sequences (total over 3,000,000 sequences) with each of the EVEREST families. EVEREST annotates 64% of all sequences, and covers 59% of all residues. EVEREST is available at http://www.everest.cs.huji.ac.il/. The website provides annotations given by SCOP, CATH, Pfam A and EVEREST. It allows for browsing through the families of each of those sources, graphically visualizing the domain organization of the proteins in the family. The website also provides access to analyzes of relationships between domain families, within and across domain definition systems. Users can upload sequences for analysis by the set of EVEREST families. Finally an advanced search form allows querying for families matching criteria regarding novelty, phylogenetic composition and more.

Amino Acid Sequence↗

PubMed2026

CERTOMICS: trusted single-cell multiomics pipeline for high-resolution profiling of adoptive cellular immunotherapies.

SUMMARY: Adoptive cellular immunontherapies, such as chimeric antigen receptor (CAR) T cell therapy, have transformed cancer treatment, yet challenges such as resistance, relapse, and high costs limit their efficacy and accessibility. A comprehensive understanding of cellular heterogeneity and molecular profiles is essential to improve these therapies. Advanced single-cell multiomics technologies have the power to analyze the complex interactions between CAR-engineered cells, immune cells, and tumor cells. However, standardized single-cell multiomics computational pipelines specifically tailored to CAR-engineered cell products are lacking. Due to the synthetic nature of CAR transgenes, additional steps for reliable identification and characterization of CAR-positive cells are required but not included in existing data-processing workflows. To address this, we present CERTOMICS, a Nextflow-based, CAR-aware pipeline offering enhanced CERTainty in immunophenotyping and data interpretation, tailored for single-cell multiOMICSprofiling of adoptive cellular immunotherapies. The pipeline standardizes processing 10x Genomics single-cell multiomics data and integrates CAR-specific identification and quality control. Additionally, a curated repository of CAR construct sequences and annotation data is provided, serving as an extensible resource to support the analysis and development of CAR T cell therapies. AVAILABILITY AND IMPLEMENTATION: Detailed documentation of this pipeline, along with a resource on latest FDA-approved CAR therapies is available on our website: https://fraunhofer-izi.github.io/Living-Drugs-Wiki/. The data underlying this article are available on GitHub at https://github.com/fraunhofer-izi/CERTOMICS. The code is also published on Zenodo at https://doi.org/10.5281/zenodo.18709693.

Multiomics↗

PubMed2002

Gramene, a tool for grass genomics.

Gramene (http://www.gramene.org) is a comparative genome mapping database for grasses and a community resource for rice (Oryza sativa). It combines a semi-automatically generated database of cereal genomic and expressed sequence tag sequences, genetic maps, map relations, and publications, with a curated database of rice mutants (genes and alleles), molecular markers, and proteins. Gramene curators read and extract detailed information from published sources, summarize that information in a structured format, and establish links to related objects both inside and outside the database, providing seamless connections between independent sources of information. Genetic, physical, and sequence-based maps of rice serve as the fundamental organizing units and provide a common denominator for moving across species and genera within the grass family. Comparative maps of rice, maize (Zea mays), sorghum (Sorghum bicolor), barley (Hordeum vulgare), wheat (Triticum aestivum), and oat (Avena sativa) are anchored by a set of curated correspondences. In addition to sequence-based mappings found in comparative maps and rice genome displays, Gramene makes extensive use of controlled vocabularies to describe specific biological attributes in ways that permit users to query those domains and make comparisons across taxonomic groups. Proteins are annotated for functional significance using gene ontology terms that have been adopted by numerous model species databases. Genetic variants including phenotypes are annotated using plant ontology terms common to all plants and trait ontology terms that are specific to rice. In this paper, we present a brief overview of the search tools available to the plant research community in Gramene.

Avena↗