Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Recognition of higher order patterns in proteins: immunologic kernels.

ABSTRACT: By applying analysis of the principal components of amino acid physical properties we predicted cathepsin cleavage sites, MHC binding affinity, and probability of B-cell epitope binding of peptides in tetanus toxin and in ten diverse additional proteins. Cross-correlation of these metrics, for peptides of all possible amino acid index positions, each evaluated in the context of a ±25 amino acid flanking region, indicated that there is a strongly repetitive pattern of short peptides of approximately thirty amino acids each bounded by cathepsin cleavage sites and each comprising B-cell linear epitopes, MHC-I and MHC-II binding peptides. Such "immunologic kernel" peptides comprise all signals necessary for adaptive immunologic cognition, response and recall. The patterns described indicate a higher order spatial integration that forms a symbolic logic coordinating the adaptive immune system.

SUBMITTER: Bremel RD

PROVIDER: S-EPMC3726486 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Recognition of higher order patterns in proteins: immunologic kernels.

Bremel Robert D RD Homan E Jane EJ

PloS one 20130729 7

By applying analysis of the principal components of amino acid physical properties we predicted cathepsin cleavage sites, MHC binding affinity, and probability of B-cell epitope binding of peptides in tetanus toxin and in ten diverse additional proteins. Cross-correlation of these metrics, for peptides of all possible amino acid index positions, each evaluated in the context of a ±25 amino acid flanking region, indicated that there is a strongly repetitive pattern of short peptides of approximat ...[more]

PMID: 23922927

Similar Datasets

HORIBALFRE program: Higher Order Residue Interactions Based ALgorithm for Fold REcognition.

Project description:Understanding the functional and structural implication of a protein encoded in novel genes using function association or fold recognition approaches remains to be a challenging task in the current era of genomes, metagenomes and personal genomes. In an attempt to enhance potential-based fold-recognition methods in recognizing remote homology between proteins, we propose a new approach "Higher Order Residue Interaction Based ALgorithm for Fold REcognition (HORIBALFRE)". Higher order residue interactions refer to a class of interactions in protein structures mediated by C(?) or C(?) atoms within a pre-defined distance cut-off. Higher order residue interactions (pairwise, triplet and quadruplet interactions) play a vital role in attaining the stable conformation of a protein structure. In HORIBALFRE, we incorporated the potential contributions from two body (pairwise) interactions, three body (triplet interactions) and four-body (quadruple interaction) interactions, to implement a new fold recognition algorithm. Core of HORIBALFRE algorithm includes the potentials generated from a library of protein structure derived from manually curated CAMPASS database of structure based sequence alignment. We used Fischer's dataset, with 68 templates and 56 target sequences, derived from SCOP database and performed one-against-all sequence alignment using TCoffee. Various potentials were derived using custom scripts and these potentials were incorporated in the HORIBALFRE algorithm. In this manuscript, we report outline of a novel fold recognition algorithm and initial results. Our results show that inclusion of quadruplet class of higher order residue interaction improves fold recognition.

| S-EPMC3280490 | biostudies-literature

Prevalence and patterns of higher-order drug interactions in Escherichia coli.

Project description:Interactions and emergent processes are essential for research on complex systems involving many components. Most studies focus solely on pairwise interactions and ignore higher-order interactions among three or more components. To gain deeper insights into higher-order interactions and complex environments, we study antibiotic combinations applied to pathogenic Escherichia coli and obtain unprecedented amounts of detailed data (251 two-drug combinations, 1512 three-drug combinations, 5670 four-drug combinations, and 13608 five-drug combinations). Directly opposite to previous assumptions and reports, we find higher-order interactions increase in frequency with the number of drugs in the bacteria's environment. Specifically, as more drugs are added, we observe an elevated frequency of net synergy (effect greater than expected based on independent individual effects) and also increased instances of emergent antagonism (effect less than expected based on lower-order interaction effects). These findings have implications for the potential efficacy of drug combinations and are crucial for better navigating problems associated with the combinatorial complexity of multi-component systems.

| S-EPMC6119685 | biostudies-literature

Diverse adult stem cells share specific higher-order patterns of gene expression.

Project description:Adult tissue stem cells (SCs) share functional properties regardless of their tissue of residence. It had been thought that SCs might also share expression of certain "stemness" genes, although early investigations for such genes were unsuccessful. Here, we show that SCs from diverse tissues do preferentially express certain types of genes and that SCs resemble other SCs in terms of global gene expression more than they resemble the differentiated cells (DCs) of the tissues that they supply. Genes associated with nuclear function and RNA binding were over-represented in SCs. In contrast, DCs from diverse tissues shared enrichment in genes associated with extracellular space, signal transduction, and the plasma membrane. Further analysis showed that transit-amplifying cells could be distinguished from both SCs and DCs by heightened expression of cell division and DNA repair genes and decreased expression of apoptosis-related genes. This transit-amplifying cell-specific signature was confirmed by de novo generation of a global expression profile of a cell population highly enriched for transit-amplifying cells: colonic crypt-base columnar cells responding to mucosal injury. Thus, progenitor cells preferentially express intracellular or biosynthetic genes, and differentiation correlates with increased expression of genes for interacting with other cells or the microenvironment. The higher-order, Gene Ontology term-based analysis we use to distinguish SC- and DC-associated gene expression patterns can also be used to identify intermediate differentiation states (e.g., that of transit-amplifying cells) and, potentially, any biological state that is reflected in changes in global gene expression patterns. Disclosure of potential conflicts of interest is found at the end of this article.

| S-EPMC2610416 | biostudies-literature

Assessing reliable human mobility patterns from higher order memory in mobile communications.

Project description:Understanding how people move within a geographical area, e.g. a city, a country or the whole world, is fundamental in several applications, from predicting the spatio-temporal evolution of an epidemic to inferring migration patterns. Mobile phone records provide an excellent proxy of human mobility, showing that movements exhibit a high level of memory. However, the precise role of memory in widely adopted proxies of mobility, as mobile phone records, is unknown. Here we use 560 million call detail records from Senegal to show that standard Markovian approaches, including higher order ones, fail in capturing real mobility patterns and introduce spurious movements never observed in reality. We introduce an adaptive memory-driven approach to overcome such issues. At variance with Markovian models, it is able to realistically model conditional waiting times, i.e. the probability to stay in a specific area depending on individuals' historical movements. Our results demonstrate that in standard mobility models the individuals tend to diffuse faster than observed in reality, whereas the predictions of the adaptive memory approach significantly agree with observations. We show that, as a consequence, the incidence and the geographical spread of a disease could be inadequately estimated when standard approaches are used, with crucial implications on resources deployment and policy-making during an epidemic outbreak.

| S-EPMC5014054 | biostudies-literature

Higher-order patterns of aquatic species spread through the global shipping network.

Project description:The introduction and establishment of nonindigenous species (NIS) through global ship movements poses a significant threat to marine ecosystems and economies. While ballast-vectored invasions have been partly addressed by some national policies and an international agreement regulating the concentrations of organisms in ballast water, biofouling-vectored invasions remain largely unaddressed. Development of additional efficient and cost-effective ship-borne NIS policies requires an accurate estimation of NIS spread risk from both ballast water and biofouling. We demonstrate that the first-order Markovian assumption limits accurate modeling of NIS spread risks through the global shipping network. In contrast, we show that higher-order patterns provide more accurate NIS spread risk estimates by revealing indirect pathways of NIS transfer using Species Flow Higher-Order Networks (SF-HON). Using the largest available datasets of non-indigenous species for Europe and the United States, we then compare SF-HON model predictions against those from networks that consider only first-order connections and those that consider all possible indirect connections without consideration of their significance. We show that not only SF-HONs yield more accurate NIS spread risk predictions, but there are important differences in NIS spread via the ballast and biofouling vectors. Our work provides information that policymakers can use to develop more efficient and targeted prevention strategies for ship-borne NIS spread management, especially as management of biofouling is of increasing concern.

| S-EPMC7394518 | biostudies-literature

Interrogating the higher order structures of snake venom proteins

Project description:Snake venoms contain complex mixtures of proteins that play vital roles in the survival of venomous snakes. In line with their diverse pharmacological activities, the protein compositions of snake venoms can be highly variable, and efforts to characterise the primary structures of such proteins are extensive and ongoing. In addition, a significant knowledge gap exists in terms of higher-order interactionsbetweenproteinsproposedto modulate venom potency, which poses a challenge for treatment of envenomation and development of successful therapeutic applications.Here we use a multifaceted mass spectrometrybased approach to characteriseproteinsfrom the medically significant venomsof Collett’s snake Pseudechis collettiand the puff adder Bitis arietans.Following chromatographic fractionation and bottom-up proteomics identification, native mass spectrometry identified, among other components, a 117 kDa non-covalent L-amino acid oxidase dimer in the P. collettivenom and a 60 kDa C-type lectin tetramer in the B. arietansvenom. Furthermore, a 27.7 kDa covalently-linked phospholipase A2(PLA2) dimer was identified in P. collettivenom, and thePLA2species were shownto adopt a highly compact geometry based on ion mobility measurements. Exploration of the catalytic efficiencies of the monomeric and dimeric forms of PLA2revealed that the dimeric PLA2 possessed greater bioactivity than the monomeric PLA2s.This work contributes to ongoing efforts to catalogue the protein components of snake venoms, and notably,itemphasises the importance of understanding higher-order protein interactions in venomsand the utility of a combined mass spectrometric approachfor this task.

2020-02-17 | PXD016503 | Pride

Genome-wide profiling of DNA repair proteins identifies higher-order coordination in single cells

Project description:Accurate repair of DNA damage is critical for maintenance of genomic integrity and cellular viability. Because damage occurs non-uniformly across the genome, single-cell resolution is required for proper interrogation, but sensitive detection has remained challenging. Here, we present a comprehensive analysis of repair protein localization in single cells using DamID and ChIC sequencing techniques. This study reports genome-wide binding profiles in response to DNA double-strand breaks induced by AsiSI, and explores variability in genomic damage locations and associated repair features in the context of spatial genome organization. By unbiasedly detecting repair factor localization, we find that repair proteins often occupy entire topologically associating domains, mimicking variability in chromatin loop anchoring. Moreover, we demonstrate the formation of multi-way chromatin hubs in response to DNA damage. Notably, larger hubs show increased coordination of repair protein binding, suggesting a preference for cooperative repair mechanisms. Together, our work offers new insights into the heterogeneous processes underlying genome stability in single cells.

2024-04-17 | GSE229874 | GEO

Higher-Order Structure Influences the Kinetics of Diethylpyrocarbonate Covalent Labeling of Proteins.

Project description:The combination of covalent labeling (CL) and mass spectrometry (MS) has emerged as a useful tool for studying protein structure due to its good structural coverage, the ability to study proteins in mixtures, and its high sensitivity. Diethylpyrocarbonate (DEPC) is an effective CL reagent that can label N-termini and the side chains of several nucleophilic residues, providing information for about 30% of the residues in the average protein. For DEPC to provide accurate structural information, the extent of labeling must be controlled to minimize label-induced structural perturbations. In this work, we establish a quantitative correlation between general protein structural factors and DEPC reaction rates by measuring the reaction rate coefficients for several model proteins. Using principal component and regression analyses, we find that the solvent accessible surface areas of histidine and lysine residues in proteins are the primary factors that determine a protein's reactivity toward DEPC, despite the fact that other more abundant residues, such as tyrosine, threonine, and serine, are also labeled by DEPC. From the statistical analysis, a model emerges that can be used to predict the reactivity of a protein based on its structure and sequence, allowing the optimal DEPC concentration to be chosen for a given protein. The resulting model is supported by cross-validation studies and by accurately predicting of the reactivity of five test proteins. Overall, our model reveals interesting insight into the reactivity of proteins with DEPC, and it will facilitate identification of optimal DEPC labeling conditions for proteins.

| S-EPMC7077735 | biostudies-literature

Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes.

Project description:Exosomes are secreted organelles that have the same topology as the cell and bud outward (outward is defined as away from the cytoplasm) from endosome membranes or endosome-like domains of plasma membrane. Here we describe an exosomal protein-sorting pathway in Jurkat T cells that selects cargo proteins on the basis of both higher-order oligomerization (the oligomerization of oligomers) and plasma membrane association, acts on proteins seemingly without regard to their function, sequence, topology, or mechanism of membrane association, and appears to operate independently of class E vacuolar protein-sorting (VPS) function. We also show that higher-order oligomerization is sufficient to target plasma membrane proteins to HIV virus-like particles, that diverse Gag proteins possess exosomal-sorting information, and that higher-order oligomerization is a primary determinant of HIV Gag budding/exosomal sorting. In addition, we provide evidence that both the HIV late domain and class E VPS function promote HIV budding by unexpectedly complex, seemingly indirect mechanisms. These results support the hypothesis that HIV and other retroviruses are generated by a normal, nonviral pathway of exosome biogenesis.

| S-EPMC1885833 | biostudies-literature

Unique Neural Activity Patterns Among Lower Order Cortices and Shared Patterns Among Higher Order Cortices During Processing of Similar Shapes With Different Stimulus Types.

Project description:We investigated the neural mechanism of the processing of three-dimensional (3D) shapes defined by disparity and perspective. We measured blood oxygenation level-dependent signals as participants viewed and classified 3D images of convex-concave shapes. According to the cue (disparity or perspective) and element type (random dots or black and white dotted lines), three types of stimuli were used: random dot stereogram, black and white dotted lines with perspective, and black and white dotted lines with binocular disparity. The blood oxygenation level-dependent images were then classified by multivoxel pattern analysis. To identify areas selective to shape, we assessed convex-concave classification accuracy with classifiers trained and tested using signals evoked by the same stimulus type (same cue and element type). To identify cortical regions with similar neural activity patterns regardless of stimulus type, we assessed the convex-concave classification accuracy of transfer classification in which classifiers were trained and tested using different stimulus types (different cues or element types). Classification accuracy using the same stimulus type was high in the early visual areas and subregions of the intraparietal sulcus (IPS), whereas transfer classification accuracy was high in the dorsal subregions of the IPS. These results indicate that the early visual areas process the specific features of stimuli, whereas the IPS regions perform more generalized processing of 3D shapes, independent of a specific stimulus type.

| S-EPMC8161881 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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