scholarly journals PIRD: Pan Immune Repertoire Database

2019 ◽  
Author(s):  
Wei Zhang ◽  
Longlong Wang ◽  
Ke Liu ◽  
Xiaofeng Wei ◽  
Kai Yang ◽  
...  
Keyword(s):  
Data Storage ◽  
High Throughput Sequencing ◽  
Homo Sapiens ◽  
Adaptive Immune System ◽  
B Cell Receptors ◽  
Sequencing Data ◽  
Immune Repertoire ◽  
Adaptive Immune ◽  
Potential Applications ◽  
Antibody Drug

Abstract Motivation T and B cell receptors (TCRs and BCRs) play a pivotal role in the adaptive immune system by recognizing an enormous variety of external and internal antigens. Understanding these receptors is critical for exploring the process of immunoreaction and exploiting potential applications in immunotherapy and antibody drug design. Although a large number of samples have had their TCR and BCR repertoires sequenced using high-throughput sequencing in recent years, very few databases have been constructed to store these kinds of data. To resolve this issue, we developed a database. Results We developed a database, the Pan Immune Repertoire Database (PIRD), located in China National GeneBank (CNGBdb), to collect and store annotated TCR and BCR sequencing data, including from Homo sapiens and other species. In addition to data storage, PIRD also provides functions of data visualization and interactive online analysis. Additionally, a manually curated database of TCRs and BCRs targeting known antigens (TBAdb) was also deposited in PIRD. Availability and implementation PIRD can be freely accessed at https://db.cngb.org/pird.

scholarly journals PIRD: Pan immune repertoire database

2018 ◽  
Author(s):  
Wei Zhang ◽  
Longlong Wang ◽  
Ke Liu ◽  
Xiaofeng Wei ◽  
Kai Yang ◽  
...  
Keyword(s):  
Data Storage ◽  
High Throughput Sequencing ◽  
Homo Sapiens ◽  
Adaptive Immune System ◽  
B Cell Receptors ◽  
Data Visualisation ◽  
Sequencing Data ◽  
Immune Repertoire ◽  
Adaptive Immune ◽  
Potential Applications

ABSTRACTMotivationT and B cell receptors (TCRs and BCRs) play a pivotal role in the adaptive immune system by recognizing an enormous variety of external and internal antigens. Understanding these receptors is critical for exploring the process of immunoreaction and exploiting potential applications in immunotherapy and antibody drug design. Although a large number of samples have had their TCR and BCR repertoires sequenced using high-throughput sequencing in recent years, very few databases have been constructed to store these kinds of data. To resolve this issue, we developed a database.ResultsWe developed a database, the Pan Immune Repertoire Database (PIRD), located in China National GeneBank (CNGBdb), to collect and store annotated TCR and BCR sequencing data, including from Homo sapiens and other species. In addition to data storage, PIRD also provides functions of data visualisation and interactive online analysis. Additionally, a manually curated database of TCRs and BCRs targeting known antigens (TBAdb) was also deposited in PIRD.Availability and ImplementationPIRD can be freely accessed at https://db.cngb.org/pird.

Plant MicroRNAs Responsive to Fungal Infection

2014 ◽  
Vol 941-944 ◽  
pp. 1141-1145 ◽  
Author(s):  
Hui Li Zhang ◽  
Lin Chen ◽  
Wen Na Li ◽  
Li Li Wang ◽  
Hong Yu Xie
Keyword(s):  
Fungal Pathogens ◽  
High Throughput Sequencing ◽  
Adaptive Immune System ◽  
Messenger Rnas ◽  
Disease Mechanism ◽  
Adaptive Immune ◽  
Alternative Approach ◽  
Crop Disease ◽  
Transcriptional Gene Regulation ◽  
And Control

MicroRNAs (miRNAs) are endogenous small RNAs transcribed from non-coding DNA, which have the capacity to base pair with the target mRNAs (messenger RNAs) to repress their translation or resulted in cleavage. We have paid much attention on the DNA and its coded proteins, the discovery of miRNAs as gene negatively regulators has led to a fundamental change in understanding of post-transcriptional gene regulation in plants. Fungal pathogens infection is the main cause of most economic crops diseases. Unlike humans, plants don’t evolved to have a adaptive immune system, they protect themselves with a mechanism consists of activation and response. Recently, high throughput sequencing validated that miRNA play a crucial role in plant-fungus interaction. A better understanding of miRNA-mediated disease mechanism in fungi should clarify the strategy of crop disease control. MiRNA-based manipulations as gene suppressors, such as artificial miRNAs, may emerge as a new alternative approach for the improvement of crops and control of crop disease.

scholarly journals Ligation-anchored PCR unveils immune repertoire of TCR-beta from whole blood

2014 ◽  
Author(s):  
Fan Gao ◽  
Kai Wang
Keyword(s):  
High Throughput Sequencing ◽  
Read Length ◽  
Integrative Approach ◽  
Sequencing Data ◽  
Immune Repertoire ◽  
Universal Primer ◽  
Illumina Hiseq ◽  
Variable Regions ◽  
Anchored Pcr ◽  
Pcr Method

Background As one of the genetic mechanisms for adaptive immunity, V(D)J recombination generates an enormous repertoire of T-cell receptors (TCRs). With the development of high-throughput sequencing techniques, systematic exploration of V(D)J recombination becomes possible. Multiplex PCR method has been previously developed to assay immune repertoire, however the usage of primer pools has inherent bias in target amplification. In our study, we developed a ligation-anchored PCR method to unbiasedly amplify the repertoire. Results By utilizing a universal primer paired with a single primer targeting the conserved constant region, we amplified TCR-beta (TRB) variable regions from total RNA extracted from blood. Next-generation sequencing libraries were then prepared for Illumina HiSeq 2500 sequencer, which provided 151 bp read length to cover the entire V(D)J recombination region. We evaluated this approach on blood samples from patients with malignant and benign meningiomas. Mapping of sequencing data showed 64% to 91% of mapped TCRV-containing reads belong to TRB subtype. An increased usage of TRBV29-1 was observed in malignant meningiomas. Also distinct signatures were identified from CDR3 sequence logos, with predominant subset as 42 nt for benign and 45 nt for malignant samples, respectively. Conclusions In summary, we report an integrative approach to monitor immune repertoire in a systematic manner.

scholarly journals SOS: online probability estimation and generation of T-and B-cell receptors

2020 ◽  
Vol 36 (16) ◽  
pp. 4510-4512
Author(s):  
Giulio Isacchini ◽  
Carlos Olivares ◽  
Armita Nourmohammad ◽  
Aleksandra M Walczak ◽  
Thierry Mora
Keyword(s):  
B Cell ◽  
High Throughput Sequencing ◽  
B Cell Receptors ◽  
Sequencing Data ◽  
Vdj Recombination ◽  
Web Based ◽  
Cell Receptors ◽  
High Throughput Sequencing Data ◽  
Selection Probabilities ◽  
Selection Of

Abstract Summary Recent advances in modelling VDJ recombination and subsequent selection of T- and B-cell receptors provide useful tools to analyse and compare immune repertoires across time, individuals and tissues. A suite of tools—IGoR, OLGA and SONIA—have been publicly released to the community that allow for the inference of generative and selection models from high-throughput sequencing data. However, using these tools requires some scripting or command-line skills and familiarity with complex datasets. As a result, the application of the above models has not been available to a broad audience. In this application note, we fill this gap by presenting Simple OLGA & SONIA (SOS), a web-based interface where users with no coding skills can compute the generation and post-selection probabilities of their sequences, as well as generate batches of synthetic sequences. The application also functions on mobile phones. Availability and implementation SOS is freely available to use at sites.google.com/view/statbiophysens/sos with source code at github.com/statbiophys/sos.

scholarly journals CasCollect: targeted assembly of CRISPR-associated operons from high-throughput sequencing data

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Joshua D Podlevsky ◽  
Corey M Hudson ◽  
Jerilyn A Timlin ◽  
Kelly P Williams
Keyword(s):  
High Throughput Sequencing ◽  
Markov Models ◽  
Adaptive Immune System ◽  
Metagenomic Data ◽  
Sequencing Data ◽  
Bacteriophage Therapy ◽  
High Throughput Sequencing Data ◽  
Assembly Pipeline ◽  
Cas Genes ◽  
Cas Proteins

Abstract CRISPR arrays and CRISPR-associated (Cas) proteins comprise a widespread adaptive immune system in bacteria and archaea. These systems function as a defense against exogenous parasitic mobile genetic elements that include bacteriophages, plasmids and foreign nucleic acids. With the continuous spread of antibiotic resistance, knowledge of pathogen susceptibility to bacteriophage therapy is becoming more critical. Additionally, gene-editing applications would benefit from the discovery of new cas genes with favorable properties. While next-generation sequencing has produced staggering quantities of data, transitioning from raw sequencing reads to the identification of CRISPR/Cas systems has remained challenging. This is especially true for metagenomic data, which has the highest potential for identifying novel cas genes. We report a comprehensive computational pipeline, CasCollect, for the targeted assembly and annotation of cas genes and CRISPR arrays—even isolated arrays—from raw sequencing reads. Benchmarking our targeted assembly pipeline demonstrates significantly improved timing by almost two orders of magnitude compared with conventional assembly and annotation, while retaining the ability to detect CRISPR arrays and cas genes. CasCollect is a highly versatile pipeline and can be used for targeted assembly of any specialty gene set, reconfigurable for user provided Hidden Markov Models and/or reference nucleotide sequences.

scholarly journals Multiscale affinity maturation simulations to elicit HIV broadly neutralizing antibodies

2021 ◽  
Author(s):  
Kayla Sprenger ◽  
Simone Conti ◽  
Victor Ovchinnikov ◽  
Arup K Chakraborty ◽  
martin karplus
Keyword(s):  
Neutralizing Antibodies ◽  
Adaptive Immune System ◽  
Multiscale Model ◽  
Cell Receptor ◽  
Affinity Maturation ◽  
Sequencing Data ◽  
Broadly Neutralizing Antibodies ◽  
Adaptive Immune ◽  
Cd4 Binding Site ◽  
Anti Hiv

The design of vaccines against highly mutable pathogens, such as HIV and influenza, requires a detailed understanding of how the adaptive immune system responds to encountering multiple variant antigens (Ags). Here, we describe a multiscale model of B cell receptor (BCR) affinity maturation that employs actual BCR nucleotide sequences and treats BCR/Ag interactions in atomistic detail. We apply the model to simulate the maturation of a broadly neutralizing Ab (bnAb) against HIV. Starting from a germline precursor sequence of the VRC01 anti-HIV Ab, we simulate BCR evolution in response to different vaccination protocols and different Ags, which were previously designed by us. The simulation results provide qualitative guidelines for future vaccine design and reveal unique insights into bnAb evolution against the CD4 binding site of HIV. Our model makes possible direct comparisons of simulated BCR populations with results of deep sequencing data, which will be explored in future applications.

scholarly journals Predicting recognition between T cell receptors and epitopes with TCRGP

2021 ◽  
Vol 17 (3) ◽  
pp. e1008814
Author(s):  
Emmi Jokinen ◽  
Jani Huuhtanen ◽  
Satu Mustjoki ◽  
Markus Heinonen ◽  
Harri Lähdesmäki
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Comprehensive Evaluation ◽  
Adaptive Immune System ◽  
Amino Acid Sequences ◽  
Sequencing Data ◽  
Cell Receptors ◽  
Adaptive Immune ◽  
Complementarity Determining Regions ◽  
Process Method

Adaptive immune system uses T cell receptors (TCRs) to recognize pathogens and to consequently initiate immune responses. TCRs can be sequenced from individuals and methods analyzing the specificity of the TCRs can help us better understand individuals’ immune status in different disorders. For this task, we have developed TCRGP, a novel Gaussian process method that predicts if TCRs recognize specified epitopes. TCRGP can utilize the amino acid sequences of the complementarity determining regions (CDRs) from TCRα and TCRβ chains and learn which CDRs are important in recognizing different epitopes. Our comprehensive evaluation with epitope-specific TCR sequencing data shows that TCRGP achieves on average higher prediction accuracy in terms of AUROC score than existing state-of-the-art methods in epitope-specificity predictions. We also propose a novel analysis approach for combined single-cell RNA and TCRαβ (scRNA+TCRαβ) sequencing data by quantifying epitope-specific TCRs with TCRGP and identify HBV-epitope specific T cells and their transcriptomic states in hepatocellular carcinoma patients.

Reduction Of Immune Repertoire Diversity Through DNA Sequence Constraints At VDJ Junctions

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4944-4944
Author(s):  
Bryan Howie ◽  
Harlan Robins ◽  
Christopher S Carlson
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Cell Receptor ◽  
Adaptive Immune System ◽  
Cell Receptor ◽  
Immune Repertoire ◽  
Adaptive Immune ◽  
Repertoire Diversity ◽  
Equity Ownership ◽  
Junctional Diversity

Abstract B and T lymphocytes are effector cells of the adaptive immune system. These cells express surface receptors that bind a huge variety of antigens, and together they comprise a person’s immune repertoire. A diverse repertoire is essential for mounting robust immune responses against a wide range of pathogens, and repertoire diversity affects the probability that DNA sequencing can uniquely tag a clonally expanded population of cells for the detection of minimum residual disease (MRD) during cancer treatment. Immune repertoire diversity arises partly through the combinatorial splicing of gene segments from the variable (V), diversity (D), and joining (J) regions of a B or T cell receptor locus. Much additional diversity is created through the stochastic insertion and deletion of nucleotides at the splice junctions, and by somatic hypermutation (SHM) in maturing lymphocytes. The generation of junctional diversity is an important part of this process, but it may be constrained by the underlying biological mechanisms. To explore the landscape of junctional diversity among immune receptor loci, we developed a likelihood model that can annotate VDJ junctions in the presence of SHM and compute the probability that a given receptor sequence was generated only once in a person’s repertoire, which is essential for tracking MRD. Using high-throughput sequencing data from several individuals and a range of receptor loci, we identify mechanistic constraints that limit B and T cell receptor diversity. For example, we show that the usual variability in CDR3 length is reduced at the immunoglobulin kappa (IgK) locus, and we connect this finding to sequence motifs that constrain nucleotide deletion at the ends of IgK gene segments. Our findings will inform future genetic studies of the adaptive immune system, and they provide quantitative guidance for deciding which cancer clones can be tracked for reliable MRD detection. Disclosures: Howie: Adaptive Biotechnologies: Employment, Equity Ownership. Robins:Adaptive Biotechnologies: Consultancy, Equity Ownership, Patents & Royalties. Carlson:Adaptive Biotechnologies: Consultancy, Equity Ownership, Patents & Royalties.

scholarly journals A Beginner’s Guide on Integrating *Omics Approaches to Study Marine Microbial Communities: Details and Discussions From Sample Collection to Bioinformatics Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Sabrina Natalie Wilms
Keyword(s):  
Single Cell ◽  
Data Storage ◽  
High Throughput Sequencing ◽  
Marine Ecosystem ◽  
Cloud Services ◽  
Small Scale ◽  
Species Differentiation ◽  
Sequencing Data ◽  
The World ◽  
Microbial Organisms

The variety of Earth’s organisms is manifold. However, it is the small-scale marine community that makes the world goes round. Microbial organisms of pro- and eukaryotic origin drive the carbon supply and nutrient cycling, thus are mediating the primary productivity within the world largest ecosystem called ocean. But due to the ocean’s great size and large number of biogeographically habitats, the total of microbial species can hardly be grabbed and therefore their functional roles not fully described. However, recent advances in high-throughput sequencing technologies are revolutionizing our understanding of the marine microbial diversity, ecology and evolution. Nowadays, research questions on species differentiation can be solved with genomic approaches such as metabarcoding, while transcriptomics offers the possibility to assign gene functions even to a single cell, e.g., single-cell transcriptomics. On the other hand, due to the diversified amount of sequencing data, the certainty of a data crisis is currently evolving. Scientists are forced to broaden their view on bioinformatics resources for analysis and data storage in from of, e.g., cloud services, to ensure the data’s exchangeability. Which is why time resources are now shifting toward solving data problems rather than answering the eco-evolutionary questions stated in the first place. This review is intended to provide exchange on *omics approaches and key points for discussions on data handling used to decipher the relevant diversity and functions of microbial organisms in the marine ecosystem.

scholarly journals Tracking SARS-CoV-2 T cells with epitope-T-cell receptor recognition models

2020 ◽  
Author(s):  
Pieter Meysman ◽  
Anna Postovskaya ◽  
Nicolas De Neuter ◽  
Benson Ogunjimi ◽  
Kris Laukens
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Adaptive Immune Response ◽  
Adaptive Immune System ◽  
Cell Receptor ◽  
Sequencing Data ◽  
Adaptive Immune ◽  
Cell Diversity ◽  
Longitudinal Profiles

Much is still not understood about the human adaptive immune response to SARS-CoV-2, the causative agent of COVID-19. In this paper, we demonstrate the use of machine learning to classify SARS-CoV-2 epitope specific T-cell clonotypes in T-cell receptor (TCR) sequencing data. We apply these models to public TCR data and show how they can be used to study T-cell longitudinal profiles in COVID-19 patients to characterize how the adaptive immune system reacts to the SARS-CoV-2 virus. Our findings confirm prior knowledge that SARS-CoV-2 reactive T-cell diversity increases over the course of disease progression. However our results show a difference between those T cells that react to epitope unique to SARS-CoV-2, which show a more prominent increase, and those T cells that react to epitopes common to other coronaviruses, which begin at a higher baseline.

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