The advance of next generation sequencing (NGS) techniques provides an unprecedented opportunity to probe the enormous diversity of the immune repertoire by deep sequencing T-cell receptors (TCRs) and B-cell receptors (BCRs). However, an efficient and accurate analytical tool is still on demand to process the huge amount of data. We have developed a high-resolution analytical pipeline, Immune Monitor ("IMonitor") to tackle this task. This method utilizes realignment to identify V(D)J genes and alleles after common local alignment. We compare IMonitor with other published tools by simulated and public rearranged sequences, and it demonstrates its superior performance in most aspects. Together with this, a methodology is developed to correct the PCR and sequencing errors and to minimize the PCR bias among various rearranged sequences with different V and J gene families. IMonitor provides general adaptation for sequences from all receptor chains of different species and outputs useful statistics and visualizations. In the final part of this article, we demonstrate its application on minimal residual disease detection in patients with B-cell acute lymphoblastic leukemia. In summary, this package would be of widespread usage for immune repertoire analysis.KEYWORDS next generation sequencing; bioinformatics; immune repertoire; TCR/BCR T HE diversity of T-cell receptors (TCRs), B-cell receptors (BCRs), and secreting form antibodies makes up the core of the complicated immune system and serves as pivotal defensive components to protect the body against invading virus, bacteria, and other pathogens. The TCR consists of a heterodimeric ab chain (95%, TRA, TRB) or gd chain (5%), while the BCR is assembled with two heavy chains (IGH) and two light chains (IGK or IGL). Structurally, each chain can be divided into the variable domain and the constant domain (Lefranc and Lefranc 2001a,b). The diversity of the TCR and BCR repertoire is enormous, owing to the process of V(D)J gene rearrangement, random deletion of germline nucleotides, and insertion of uncertain length of nontemplate nucleotides between V-D and D-J junctions (TRB, IGH) or V-J junctions (TRA, IGK, IGL). In humans, it has been estimated theoretically that the diversity of TCR-ab receptors exceeds 10 18 in the thymus, and the diversity of the B-cell repertoire is even larger, considering the somatic hypermutation (Janeway 2005;Benichou et al. 2012). The T-and B-cell repertoire could undergo dynamic changes under different phenotypic status. Recently, deep sequencing enabled by different platforms including Roche 454 and Illumina Hiseq (Freeman et al. 2009;Robins et al. 2009;Wang et al. 2010;Fischer 2011;Venturi et al. 2011) has been applied to unravel the dynamics of the TCR and BCR repertoire and extended to various translational applications such as vaccination, cancer, and autoimmune diseases.Several tools and software have been developed for TCR and BCR sequence analysis, including iHMMune-align (Gaeta et al. 2007), HighV-QEUST (Li et al. 2013), IgBLA...

Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.69 × 10−7), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci—PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser—also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2, is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association (P<0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD.

The detailed frequencies distribution of ABO alleles was studied in the Chinese Han population. We identified 14 alleles, including 3 novel alleles.

There are significant differences in the frequencies and molecular characteristics of D variants among indigenous Chinese populations, compared to Caucasian and African populations, which must be considered when developing clinical practices related to D variant blood donors, transfusion recipients, or obstetrical patients.