Dataset Information

Precise tracking of vaccine-responding T cell clones reveals convergent and personalized response in identical twins.

ABSTRACT: T cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical framework to detect TCR clone proliferation and contraction from longitudinal repertoire data. We applied this framework to data from three pairs of identical twins immunized with the yellow fever vaccine. We identified 600 to 1,700 responding TCRs in each donor and validated them using three independent assays. While the responding TCRs were mostly private, albeit with higher overlap between twins, they could be well-predicted using a classifier based on sequence similarity. Our method can also be applied to samples obtained postinfection, making it suitable for systematic discovery of new infection-specific TCRs in the clinic.

SUBMITTER: Pogorelyy MV

PROVIDER: S-EPMC6294963 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Precise tracking of vaccine-responding T cell clones reveals convergent and personalized response in identical twins.

Pogorelyy Mikhail V MV Minervina Anastasia A AA Touzel Maximilian Puelma MP Sycheva Anastasiia L AL Komech Ekaterina A EA Kovalenko Elena I EI Karganova Galina G GG Egorov Evgeniy S ES Komkov Alexander Yu AY Chudakov Dmitriy M DM Mamedov Ilgar Z IZ Mora Thierry T Walczak Aleksandra M AM Lebedev Yuri B YB

Proceedings of the National Academy of Sciences of the United States of America 20181120 50

T cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical framework to detect TCR clone proliferation and contraction from longitudinal repertoire data. We applied this framework to data from three pairs of identical twins immunized with the yellow fever vaccine. We identified 600 to 1,700 responding TCRs in each donor and ...[more]

PMID: 30459272

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Project description:Background:A gap exists in our mechanistic understanding of how genetic and environmental risk factors converge at the molecular level to result in the emergence of autism symptoms. We compared blood-based gene expression signatures in identical twins concordant and discordant for autism spectrum condition (ASC) to differentiate genetic and environmentally driven transcription differences, and establish convergent evidence for biological mechanisms involved in ASC. Methods:Genome-wide gene expression data were generated using RNA-seq on whole blood samples taken from 16 pairs of monozygotic (MZ) twins and seven twin pair members (39 individuals in total), who had been assessed for ASC and autism traits at age 12. Differential expression (DE) analyses were performed between (a) affected and unaffected subjects (N?=?36) and (b) within discordant ASC MZ twin pairs (total N?=?11) to identify environmental-driven DE. Gene set enrichment and pathway testing was performed on DE gene lists. Finally, an integrative analysis using DNA methylation data aimed to identify genes with consistent evidence for altered regulation in cis. Results:In the discordant twin analysis, three genes showed evidence for DE at FDR?<?10%: IGHG4, EVI2A and SNORD15B. In the case-control analysis, four DE genes were identified at FDR?<?10% including IGHG4, PRR13P5, DEPDC1B, and ZNF501. We find enrichment for DE of genes curated in the SFARI human gene database. Pathways showing evidence of enrichment included those related to immune cell signalling and immune response, transcriptional control and cell cycle/proliferation. Integrative methylomic and transcriptomic analysis identified a number of genes showing suggestive evidence for cis dysregulation. Limitations:Identical twins stably discordant for ASC are rare, and as such the sample size was limited and constrained to the use of peripheral blood tissue for transcriptomic and methylomic profiling. Given these primary limitations, we focused on transcript-level analysis. Conclusions:Using a cohort of ASC discordant and concordant MZ twins, we add to the growing body of transcriptomic-based evidence for an immune-based component in the molecular aetiology of ASC. Whilst the sample size was limited, the study demonstrates the utility of the discordant MZ twin design combined with multi-omics integration for maximising the potential to identify disease-associated molecular signals.

Dataset Information

Precise tracking of vaccine-responding T cell clones reveals convergent and personalized response in identical twins.

Publications

Precise tracking of vaccine-responding T cell clones reveals convergent and personalized response in identical twins.

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