Chemical features of blood-borne TRG CDR3s associated with an increased overall survival in breast cancer

Chobrutskiy, Andrea; Chobrutskiy, Boris I.; Zaman, Saif; Hsiang, Monica; Blanck, George

doi:10.1007/s10549-020-05996-6

Cited by 14 publications

(13 citation statements)

References 27 publications

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“…These software modules follow the precedents of the Pappu lab (21). The CDR3 AA chemical sequence motifs were established for each CDR3 according to reference (18) and Table SIII; and the python code used to make the symbol replacements to establish the chemical sequence motifs is freely available at https://github. com/bchobrut-USF/brca_motif.…”

Section: Methodsmentioning

confidence: 99%

“…Survival distinctions. Survival distinctions based on the single value, physicochemical features of the CDR3 AA sequences were assessed as described (12), with an example output in Table SIV; and survival distinctions based on the AA chemical sequence motif approach were assessed as previously indicated (18), with example outputs in Tables SV-SXII, representing Table I in the results section below.…”

Section: Methodsmentioning

confidence: 99%

“…breast cancer B-cell receptor CDR3s revealed not only a strong survival distinction when those assessments included an assessment of the chemical interaction potential of same-patient TP53 mutants but also revealed clear associations of immune markers with the higher surviving, chemical complementarity group. More recently, the chemical sequence motif approach, which preserves the presumed AA sequence functional role in the physicochemical assignments and which has already been employed in immune repertoire approaches (17), has been applied to IR CDR3s, and to CDR3-antigen matching algorithms, where the IR CDR3s have been identified in large genomics file sets (10,18). For example, an algorithm for establishing basic chemical complementarity over a large dataset of CDR3s and mutants, that employed a chemical sequence motif approach, identified correlations between TRG CDR3, AA sequence-PIK3CA mutant chemical complementarity and survival rates and immune marker expression (10).…”

Section: Immune Receptor Cdr3 Chemical Features That Preserve Sequenc...mentioning

confidence: 99%

“…Patients representing the highest chemical complementarity scores also represented the highest survival. In another case, the chemical sequence motif, survival distinctions were established with blood resident, TRG CDR3 AA chemical sequence motifs in the absence of any potential assessments of chemically complementary antigens (18). Given the high likelihood of continued characterizations of immune receptor CDR3 chemical features for either antigen identification or basic correlative work, it became of interest to make a comparison of the potential of a relatively simple, single value physicochemical parameter to represent the CDR3 AA sequence, which is efficient in a big data setting, compared with the value of the chemical sequence motif approach, which is more processing intensive for all subsequent correlative or chemical interaction approaches and which may be overly restrictive for correlative studies and biomarker discovery.…”

Section: Immune Receptor Cdr3 Chemical Features That Preserve Sequenc...mentioning

confidence: 99%

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Immune receptor CDR3 chemical features that preserve sequence information are highly efficient in reflecting survival distinctions: A pan‑cancer analysis

Mcbreairty

Chobrutskiy

et al. 2022

Biomed Rep

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Adaptive immune receptor (IR) chemical features have been used as signatures of an immune response for numerous medical conditions, raising the question of whether certain approaches to assessing the IR chemical features are more robust than others? In the cancer setting, a very large dataset of IR complementarity determining region-3 (CDR3) amino acid (AA) sequences has become available via the mining of cancer specimen and blood genomics files for IR recombination reads. The IR CDR3 AA sequences have been evaluated for chemical features, and survival rates have been correlated with distinct chemical features. Two common approaches have been i) to assign a single value to the CDR3, representing a chemical attribute, such as aromaticity; or ii) to reduce the actual CDR3 AA sequence to a chemical sequence motif, which merges similar CDR3 chemistries represented by distinct AA sequences but preserves potential functional aspects of the order of the AAs in the sequence. While a controlled comparison of the two approaches is not possible, the application of the two approaches to the same clinical datasets offers the opportunity to appreciate a trend with regard to the overall potential in distinguishing survival probabilities. We demonstrate that application of the chemical sequence motif approach is more likely to identify survival distinctions within cancer datasets, for both tumor specimen and blood sourced, adaptive IR CDR3 AA sequences.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Immune Receptor Cdr3 Chemical Features That Preserve Sequenc...mentioning

confidence: 99%

Section: Immune Receptor Cdr3 Chemical Features That Preserve Sequenc...mentioning

confidence: 99%

See 2 more Smart Citations

Immune receptor CDR3 chemical features that preserve sequence information are highly efficient in reflecting survival distinctions: A pan‑cancer analysis

Mcbreairty

Chobrutskiy

et al. 2022

Biomed Rep

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“…Recent work has linked CDR3 AA physical-chemical attributes to survival distinctions, particularly for the CDR3s derived from the WXS-files(Arturo et al, 2020;Chobrutskiy et al, 2021; …”

mentioning

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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IGL CDR3 Hydropathy and Antigen Chemical Complementarity Associated with Greater Disease-Free Survival in Lung Adenocarcinoma: Implications for Gender Disparities

et al. 2023

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Chemical features of blood-borne TRG CDR3s associated with an increased overall survival in breast cancer

Cited by 14 publications

References 27 publications

Immune receptor CDR3 chemical features that preserve sequence information are highly efficient in reflecting survival distinctions: A pan‑cancer analysis

Immune receptor CDR3 chemical features that preserve sequence information are highly efficient in reflecting survival distinctions: A pan‑cancer analysis

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

IGL CDR3 Hydropathy and Antigen Chemical Complementarity Associated with Greater Disease-Free Survival in Lung Adenocarcinoma: Implications for Gender Disparities

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