Recovery of T-cell receptor V(D)J recombination reads from lower grade glioma exome files correlates with reduced survival and advanced cancer grade

Chobrutskiy, Boris I.; Zaman, Saif; Wei, Tong; Diviney, Andrea; Blanck, George

doi:10.1007/s11060-018-03001-1

Cited by 49 publications

(28 citation statements)

References 34 publications

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“…Slices of the WXS files in which TRA and TRB genes/reads are located were then downloaded to University of South Florida research computing. V(D)J recombination read recovery was performed using a collection of scripts similar to previous publications . (see Supplementary material, Computer code package A).…”

Section: Methodsmentioning

confidence: 99%

“…V(D)J recombination read recovery was performed using a collection of scripts similar to previous publications. 23,24 (see Supplementary material, Computer code package A). The standards for identification of a TRA or TRB recombination read were: (i) a > 90% nucleotide match fidelity for both V and J regions, (ii) a > 20-nucleotide match length for both V and J regions, and (iii) a CDR3 domain with no stop codons or reading frame shifts (see Supplementary material, Table S1).…”

Section: Recovery Of Immune Receptor V(d)j Recombination Readsmentioning

confidence: 99%

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A scoring system for the electrostatic complementarities of T‐cell receptors and cancer‐mutant amino acids: multi‐cancer analyses of associated survival rates

et al. 2020

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Summary The anti‐tumor immune response is considered to be due to the T‐cell receptor (TCR) binding to tumor antigens, which can be either wild‐type, early stem cell proteins, presumably foreign to a developed immune system; or mutant peptides, foreign to the immune system because of a mutant amino acid (aa) or otherwise somatically altered aa sequence. Recently, very large numbers of TCR complementarity‐determining region‐3 (CDR3) aa sequences obtained from tumor specimens have become available. We developed a novel algorithm for assessing the complementarity of tumor mutant peptides and TCR CDR3s, based on the retrieval of TCR CDR3 aa sequences from both tumor specimen and patient blood exomes and by using an automated process of assessing CDR3 and mutant aa electrical charges. Results indicated many instances where high electrostatic complementarity was associated with a higher survival rate. In particular, our approach led to the identification of specific genes contributing significantly to the complementary, TCR CDR3‐mutant aa. These results suggest a novel approach to tumor immunoscoring and may lead to the identification of high‐priority neo‐antigen, peptide vaccines; or to the identification of ex vivo stimulants of tumor‐infiltrating lymphocytes.

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Section: Methodsmentioning

confidence: 99%

Section: Recovery Of Immune Receptor V(d)j Recombination Readsmentioning

confidence: 99%

A scoring system for the electrostatic complementarities of T‐cell receptors and cancer‐mutant amino acids: multi‐cancer analyses of associated survival rates

et al. 2020

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“…This is in contrast to the first approach used above (Methods), whereby all V-gene segment matches were made only with the available nucleotides, within the candidate recombination read, on the 5' side of the conserved cysteine. This second approach was more robust and allowed more recovery of recombination reads representing IGH, where the read must have room for verifiable V-and J-gene segments, as well as the IGH D-gene segment and the remainder of the junction, non-germline amino acid sequences (28). Thus, we assessed survival rates represented by the LUAD barcodes representing recovery of all three BcR gene recombination reads in comparison to the survival rate represented by all remaining barcodes.…”

Section: Resultsmentioning

confidence: 99%

“…The current software is capable of detecting more recombinations by increasing V and J sequence searches near the N-region diversity section of the recombination (28,29).…”

Section: Discussionmentioning

confidence: 99%

B-cell Receptor Recombinations in Lung Adenocarcinoma Exome Files Correlate With a Higher Overall Survival Rate

Wei

Callahan

et al. 2020

Anticancer Res

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Background/Aim: While there has been a rapid development in genomic data mining approaches for T-cell receptor recombinations (TcR), less emphasis has been placed on B-cell receptor (BcR) recombinations. Materials and Methods: We obtained lung cancer exome files from the cancer genome atlas (TCGA) and mined the files for TcR and BcR recombination reads. Results: There was a robust detection of BcR light chain recombination reads in lung adenocarcinoma (TCGA-LUAD) samples, and there was a correlation between the detection of light chain recombination reads and a more favorable outcome. This result was supported by analyses of the expression of B-cell markers as indicated by LUAD RNASeq files. Conclusion: BcR and TcR recombination reads recovered from LUAD WXS files, either alone or in combination with the human leukocyte antigen (HLA) type, are likely to have prognostic value.

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“…In particular, the below comparison of the information gained via recovery of immune receptor (IR) recombinations from the two different sources was motivated primarily by the fact that the approach used for the WXS-based recoveries (B. I. Chobrutskiy et al, 2018) yielded far fewer IR recombinations than the approach for the RNAseq-based recoveries, representing a separate research group (Thorsson et al, 2018). Some of the differences in the datamining approaches are referred to in Discussion, but the fact that far fewer case IDs were represented by the WXS-based recovery process has raised the question of whether practical uses of the immune receptor recovery information were consistent.…”

Section: Introductionmentioning

confidence: 99%

A comparison of immune receptor recombination databases sourced from tumour exome or RNAseq files: Verifications of immunological distinctions between primary and metastatic melanoma

Patel

Yeagley

Arturo

et al. 2021

Int J Immunogenetics

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It became apparent several years ago that RNAseq and exome files prepared from tissue could be mined for adaptive immune receptor (IR) recombinations, which has given extra value to datasets originally intended for gene expression or mutation studies. For example, recovery of IR recombination reads from tumour specimen genomics files can correlate with survival rates. In particular, many benchmarking processes have been applied to the two sets of the IR recombination reads obtained from the cancer genome atlas files, but these two sets have never been directly compared.Here we show that both sets largely agree regarding several parameters. For example, recovery of TRB recombination reads from both WXS and RNAseq files representing metastatic melanoma was associated with a better outcome (p < .0004 in both cases); and T-cell receptor recombination read recovery, for both genomics file types, associated very strongly with T-cell gene expression markers. However, the use of CDR3 chemical features for survival distinctions was not consistent. This topic, and the surprising result that both datasets indicated that primary melanoma with recovery of IR recombination reads, in stark contrast to metastatic melanoma, represents a worse outcome, are discussed.

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Recovery of T-cell receptor V(D)J recombination reads from lower grade glioma exome files correlates with reduced survival and advanced cancer grade

Cited by 49 publications

References 34 publications

A scoring system for the electrostatic complementarities of T‐cell receptors and cancer‐mutant amino acids: multi‐cancer analyses of associated survival rates

A scoring system for the electrostatic complementarities of T‐cell receptors and cancer‐mutant amino acids: multi‐cancer analyses of associated survival rates

B-cell Receptor Recombinations in Lung Adenocarcinoma Exome Files Correlate With a Higher Overall Survival Rate

A comparison of immune receptor recombination databases sourced from tumour exome or RNAseq files: Verifications of immunological distinctions between primary and metastatic melanoma

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