TCRklass: a new K-string-based algorithm for human and mouse TCR repertoire characterization.

The next-generation sequencing technology has promoted the study on human TCR repertoire, which is essential for the adaptive immunity. To decipher the complexity of TCR repertoire, we developed an integrated pipeline, TCRklass, using K-string-based algorithm that has significantly improved the accuracy and performance over existing tools. We tested TCRklass using manually curated short read datasets in comparison with in silico datasets; it showed higher precision and recall rates on CDR3 identification. We applied TCRklass on large datasets of two human and three mouse TCR repertoires; it demonstrated higher reliability on CDR3 identification and much less biased V/J profiling, which are the two components contributing the diversity of the repertoire. Because of the sequencing cost, short paired-end reads generated by next-generation sequencing technology are and will remain the main source of data, and we believe that the TCRklass is a useful and reliable toolkit for TCR repertoire analysis.

Yang X ，Liu D ，Lv N ，Zhao F ，Liu F ，Zou J ，Chen Y ，Xiao X ，Wu J ，Liu P ，Gao J ，Hu Y ，Shi Y ，Liu J ，Zhang R ，Chen C ，Ma J ，Gao GF ，Zhu B ... -  《-》

Next generation sequencing for TCR repertoire profiling: platform-specific features and correction algorithms.

The TCR repertoire is a mirror of the human immune system that reflects processes caused by infections, cancer, autoimmunity, and aging. Next generation sequencing (NGS) is becoming a powerful tool for deep TCR profiling; yet, questions abound regarding the methodological approaches for sample preparation and correct data interpretation. Accumulated PCR and sequencing errors along with library preparation bottlenecks and uneven PCR efficiencies lead to information loss, biased quantification, and generation of huge artificial TCR diversity. Here, we compare Illumina, 454, and Ion Torrent platforms for individual TCR profiling, evaluate the rate and character of errors, and propose advanced platform-specific algorithms to correct massive sequencing data. These developments are applicable to a wide variety of next generation sequencing applications. We demonstrate that advanced correction allows the removal of the majority of artificial TCR diversity with concomitant rescue of most of the sequencing information. Thus, this correction enhances the accuracy of clonotype identification and quantification as well as overall TCR diversity measurements.

Bolotin DA ，Mamedov IZ ，Britanova OV ，Zvyagin IV ，Shagin D ，Ustyugova SV ，Turchaninova MA ，Lukyanov S ，Lebedev YB ，Chudakov DM ... -  《-》

Tools for fundamental analysis functions of TCR repertoires: a systematic comparison.

The full set of T cell receptors (TCRs) in an individual is known as his or her TCR repertoire. Defining TCR repertoires under physiological conditions and in response to a disease or vaccine may lead to a better understanding of adaptive immunity and thus has great biological and clinical value. In the past decade, several high-throughput sequencing-based tools have been developed to assign TCRs to germline genes and to extract complementarity-determining region 3 (CDR3) sequences using different algorithms. Although these tools claim to be able to perform the full range of fundamental TCR repertoire analyses, there is no clear consensus of which tool is best suited to particular projects. Here, we present a systematic analysis of 12 available TCR repertoire analysis tools using simulated data, with an emphasis on fundamental analysis functions. Our results shed light on the detailed functions of TCR repertoire analysis tools and may therefore help researchers in the field to choose the right tools for their particular experimental design.

Zhang Y ，Yang X ，Zhang Y ，Zhang Y ，Wang M ，Ou JX ，Zhu Y ，Zeng H ，Wu J ，Lan C ，Zhou HW ，Yang W ，Zhang Z ... -  《-》

3D: diversity, dynamics, differential testing - a proposed pipeline for analysis of next-generation sequencing T cell repertoire data.

Zhang L ，Cham J ，Paciorek A ，Trager J ，Sheikh N ，Fong L ... -  《-》

Computational Analysis of T-Cell Receptor Repertoire Workflow: From T-Cell Isolation to Bioinformatics Analysis.

The T-cell receptor (TCR) is the key molecule involved in the adaptive immune response. It is generated by the V(D)J recombination, responsible of the enormous diversity of the TCR repertoire, a crucial feature determining the individual capability to response to antigens and to build immunological memory. A pivotal role in the recognition of antigen is played by the hypervariable complementarity-determining region 3 (CDR3) of the V-beta chain of TCR. Investigating the CDR3 supports the understanding of the adaptive immune system dynamics in physiological processes, such as immune aging, and in disease, especially autoimmune disorders in which T cells are main actors. High-throughput sequencing (HTS) paved the way for a great progress in the investigation of TCR repertoire, enhancing the read depth in the process of library generation of sequencing and the number of samples that can be analyzed simultaneously. Therefore, the leverage of big datasets stressed the need to develop computational approach, by bioinformatics, to unravel the characteristics of the TCR repertoire.

Amoriello R ，Maghrebi O ，Ballerini C 《-》