publication . Article . Other literature type . 2017

Targeted reconstruction of T cell receptor sequence from single cell RNA-seq links CDR3 length to T cell differentiation state.

Ulrike Gerdemann; Shaked Afik; Daniel C. Douek; Kathleen B. Yates; Arlene H. Sharpe; Arlene H. Sharpe; Leo Swadling; Samuel Darko; Paul Klenerman; Paul Klenerman; ...
Open Access English
  • Published: 19 Sep 2017
  • Publisher: OXFORD UNIV PRESS
Abstract
Abstract The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells. However, current methods for TCR inference from scRNA-seq are limited in their sensitivity and require long sequencing reads, thus increasing the cost and decreasing the number of cells that can be feasibly analyzed. Here we present TRAPeS, a publicly available tool...
Subjects
free text keywords: RNA characterisation and manipulation, Computational Methods, Massively Parallel (Deep) Sequencing, Methods Online, Genetics, Single-cell analysis, T cell differentiation, Computational biology, Epitope, Complementarity determining region, CD8, T-cell receptor, T cell, medicine.anatomical_structure, medicine, Cellular differentiation, Biology
Related Organizations
Funded by
NIH| Systems Biological Analysis of Innate and Adaptive Responses to Vaccination
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1U19AI090023-01
  • Funding stream: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
59 references, page 1 of 4

1. Appay,V., Dunbar,P.R., Callan,M., Klenerman,P., Gillespie,G.M.A., Papagno,L., Ogg,G.S., King,A., Lechner,F., Spina,C.A. et al. (2002) Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat. Med., 8, 379-385.

2. Newell,E.W., Sigal,N., Bendall,S.C., Nolan,G.P. and Davis,M.M. (2012) Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity, 36, 142-152.

3. Chattopadhyay,P.K. and Roederer,M. (2015) A mine is a terrible thing to waste: high content, single cell technologies for comprehensive immune analysis. Am. J. Transplant, 15, 1155-1161.

4. Fuertes Marraco,S.A., Soneson,C., Cagnon,L., Gannon,P.O., Allard,M., Maillard,S.A., Montandon,N., Rufer,N., Waldvogel,S., Delorenzi,M. et al. (2015) Long-lasting stem cell like memory CD8 T cells with a na¨ıve-like profile upon yellow fever vaccination. Sci. Transl. Med., 7, 282ra48.

5. Pulko,V., Davies,J.S., Martinez,C., Lanteri,M.C., Busch,M.P., Diamond,M.S., Knox,K., Bush,E.C., Sims,P.A., Sinari,S. et al. (2016) Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses. Nat. Immunol., 17, 966-975. [OpenAIRE]

6. Swadling,L., Capone,S., Antrobus,R.D., Brown,A., Richardson,R., Newell,E.W., Halliday,J., Kelly,C., Bowen,D., Fergusson,J. et al. (2014) A human vaccine strategy based on chimpanzee adenoviral and MVA vectors that primes, boosts, and sustains functional HCV-specific T cell memory. Sci. Transl. Med., 6, 261ra153.

7. Venturi,V., Quigley,M.F., Greenaway,H.Y., Ng,P.C., Ende,Z.S., McIntosh,T., Asher,T.E., Almeida,J.R., Levy,S., Price,D.A. et al. (2011) A mechanism for TCR sharing between T cell subsets and individuals revealed by pyrosequencing. J. Immunol., 186, 4285-4294.

8. Robins,H.S., Srivastava,S.K., Campregher,P.V., Turtle,C.J., Andriesen,J., Riddell,S.R., Carlson,C.S. and Warren,E.H. (2010) Overlap and effective size of the human CD8+ T cell receptor repertoire. Sci. Transl. Med., 2, 47ra64.

9. Venturi,V., Price,D.A., Douek,D.C. and Davenport,M.P. (2008) The molecular basis for public T-cell responses? Nat. Rev. Immunol., 8, 231-238.

10. Venturi,V., Kedzierska,K., Price,D.A., Doherty,P.C., Douek,D.C., Turner,S.J. and Davenport,M.P. (2006) Sharing of T cell receptors in antigen-specific responses is driven by convergent recombination. Proc. Natl. Acad. Sci. U.S.A., 103, 18691-18696. [OpenAIRE]

11. Ji,X., Lyu,S.-C., Spindler,M., Bacchetta,R., Goncharov,I., Han,A., Glanville,J., Wang,W., Roncarolo,M., Meyer,E. et al. (2015) Deep profiling of single T cell receptor repertoire and phenotype with targeted RNA-seq (TECH2P. 927). J. Immunol., 194, 206-237.

12. Li,B., Li,T., Pignon,J.-C., Wang,B., Wang,J., Shukla,S.A., Dou,R., Chen,Q., Hodi,F.S., Choueiri,T.K. et al. (2016) Landscape of tumor-infiltrating T cell repertoire of human cancers. Nat. Genet., 48, 725-732. [OpenAIRE]

13. Han,A., Glanville,J., Hansmann,L. and Davis,M.M. (2014) Linking T-cell receptor sequence to functional phenotype at the single-cell level. Nat. Biotechnol., 32, 684-692.

14. Li,B. and Dewey,C.N. (2011) RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics, 12, 323.

15. Stubbington,M.J.T., L o¨nnberg,T., Proserpio,V., Clare,S., Speak,A.O., Dougan,G. and Teichmann,S.A. (2016) T cell fate and clonality inference from single-cell transcriptomes. Nat. Methods, 13, 329-332. [OpenAIRE]

59 references, page 1 of 4
Abstract
Abstract The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells. However, current methods for TCR inference from scRNA-seq are limited in their sensitivity and require long sequencing reads, thus increasing the cost and decreasing the number of cells that can be feasibly analyzed. Here we present TRAPeS, a publicly available tool...
Subjects
free text keywords: RNA characterisation and manipulation, Computational Methods, Massively Parallel (Deep) Sequencing, Methods Online, Genetics, Single-cell analysis, T cell differentiation, Computational biology, Epitope, Complementarity determining region, CD8, T-cell receptor, T cell, medicine.anatomical_structure, medicine, Cellular differentiation, Biology
Related Organizations
Funded by
NIH| Systems Biological Analysis of Innate and Adaptive Responses to Vaccination
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1U19AI090023-01
  • Funding stream: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
59 references, page 1 of 4

1. Appay,V., Dunbar,P.R., Callan,M., Klenerman,P., Gillespie,G.M.A., Papagno,L., Ogg,G.S., King,A., Lechner,F., Spina,C.A. et al. (2002) Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat. Med., 8, 379-385.

2. Newell,E.W., Sigal,N., Bendall,S.C., Nolan,G.P. and Davis,M.M. (2012) Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity, 36, 142-152.

3. Chattopadhyay,P.K. and Roederer,M. (2015) A mine is a terrible thing to waste: high content, single cell technologies for comprehensive immune analysis. Am. J. Transplant, 15, 1155-1161.

4. Fuertes Marraco,S.A., Soneson,C., Cagnon,L., Gannon,P.O., Allard,M., Maillard,S.A., Montandon,N., Rufer,N., Waldvogel,S., Delorenzi,M. et al. (2015) Long-lasting stem cell like memory CD8 T cells with a na¨ıve-like profile upon yellow fever vaccination. Sci. Transl. Med., 7, 282ra48.

5. Pulko,V., Davies,J.S., Martinez,C., Lanteri,M.C., Busch,M.P., Diamond,M.S., Knox,K., Bush,E.C., Sims,P.A., Sinari,S. et al. (2016) Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses. Nat. Immunol., 17, 966-975. [OpenAIRE]

6. Swadling,L., Capone,S., Antrobus,R.D., Brown,A., Richardson,R., Newell,E.W., Halliday,J., Kelly,C., Bowen,D., Fergusson,J. et al. (2014) A human vaccine strategy based on chimpanzee adenoviral and MVA vectors that primes, boosts, and sustains functional HCV-specific T cell memory. Sci. Transl. Med., 6, 261ra153.

7. Venturi,V., Quigley,M.F., Greenaway,H.Y., Ng,P.C., Ende,Z.S., McIntosh,T., Asher,T.E., Almeida,J.R., Levy,S., Price,D.A. et al. (2011) A mechanism for TCR sharing between T cell subsets and individuals revealed by pyrosequencing. J. Immunol., 186, 4285-4294.

8. Robins,H.S., Srivastava,S.K., Campregher,P.V., Turtle,C.J., Andriesen,J., Riddell,S.R., Carlson,C.S. and Warren,E.H. (2010) Overlap and effective size of the human CD8+ T cell receptor repertoire. Sci. Transl. Med., 2, 47ra64.

9. Venturi,V., Price,D.A., Douek,D.C. and Davenport,M.P. (2008) The molecular basis for public T-cell responses? Nat. Rev. Immunol., 8, 231-238.

10. Venturi,V., Kedzierska,K., Price,D.A., Doherty,P.C., Douek,D.C., Turner,S.J. and Davenport,M.P. (2006) Sharing of T cell receptors in antigen-specific responses is driven by convergent recombination. Proc. Natl. Acad. Sci. U.S.A., 103, 18691-18696. [OpenAIRE]

11. Ji,X., Lyu,S.-C., Spindler,M., Bacchetta,R., Goncharov,I., Han,A., Glanville,J., Wang,W., Roncarolo,M., Meyer,E. et al. (2015) Deep profiling of single T cell receptor repertoire and phenotype with targeted RNA-seq (TECH2P. 927). J. Immunol., 194, 206-237.

12. Li,B., Li,T., Pignon,J.-C., Wang,B., Wang,J., Shukla,S.A., Dou,R., Chen,Q., Hodi,F.S., Choueiri,T.K. et al. (2016) Landscape of tumor-infiltrating T cell repertoire of human cancers. Nat. Genet., 48, 725-732. [OpenAIRE]

13. Han,A., Glanville,J., Hansmann,L. and Davis,M.M. (2014) Linking T-cell receptor sequence to functional phenotype at the single-cell level. Nat. Biotechnol., 32, 684-692.

14. Li,B. and Dewey,C.N. (2011) RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics, 12, 323.

15. Stubbington,M.J.T., L o¨nnberg,T., Proserpio,V., Clare,S., Speak,A.O., Dougan,G. and Teichmann,S.A. (2016) T cell fate and clonality inference from single-cell transcriptomes. Nat. Methods, 13, 329-332. [OpenAIRE]

59 references, page 1 of 4
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