Biology subjects

Liu, X.-S.

Publications and source records attributed to Liu, X.-S..

3 recordsLinked to original sources

bioRxiv2021

Essential role for Ggct in erythrocyte antioxidant defense

GGCT encodes {gamma}-glutamyl cyclotransferase enzyme activity, and its expression is up-regulated in various human cancers. {gamma}-glutamyl cyclotransferase enzyme activity was originally purified from human red blood cells (RBCs), however physiological function of GGCT in RBCs is still not clear. Here we reported that Ggct deletion in mouse leads to splenomegaly and progressive anemia phenotypes, due to elevated oxidative damage and shortened life span of Ggct-/- RBCs. Ggct-/- RBCs have increased reactive oxygen species (ROS), and are more sensitive to H2O2 induced damage compared to control RBCs. Glutathione (GSH) and GSH synthesis precursor L-cysteine are decreased in Ggct-/- RBCs. Our study suggests a critical function of Ggct in RBC redox balance and life span maintenance through regulating GSH metabolism.

genetics↗

bioRxiv2020

Sigflow: an automated and comprehensive pipeline for cancer genome mutational signature analysis

SummaryMutational signatures are recurring DNA alteration patterns caused by distinct mutational events during the evolution of cancer. In recent years, several bioinformatics tools are available for mutational signature analysis. However, most of them focus on specific type of mutation, or have limited scope of application. A pipeline tool for comprehensive mutational signature analysis is still lacking. Here we present Sigflow pipeline, which provides an one-stop solution for de novo signature extraction, reference signature fitting, signature stability analysis, sample clustering based on signature exposure in different types of genome DNA alterations including single base substitution (SBS), doublet base substitution (DBS), small insertion and deletion (INDEL), and copy number alteration. A Docker image is constructed to solve the complex and time-consuming installation issues, and this enables reproducible research by version control of all dependent tools along with their environments. The Sigflow pipeline can be applied to both human and mouse genomes. Availability and implementationSigflow is an open source software under academic free license (AFL) v3.0 and it is freely available at https://github.com/ShixiangWang/sigminer.workflow or https://hub.docker.com/r/shixiangwang/sigflow. Contactliuxs@shanghaitech.edu.cn

genomics↗

bioRxiv2020

Revisiting neoantigen depletion signal in the untreated cancer genome

This study is arising from Van den Eynden J. et al. Nature Genetics. Lack of detectable neoantigen depletion signals in the untreated cancer genome. Van den Eynden J. et al. tried to address a very important scientific question: could the immune system eliminate cancer cells with immunogenic mutations in untreated situation? Van den Eynden J. et al. first annotated the human exome into "HLA-binding regions" and "non HLA-binding regions" based on the predicted binding affinity of nonapeptides translated from the un-mutated reference coding genome with type I HLA alleles. They hypothesized that if neoantigen depletion signal exist, the nonsynonymous mutations in "HLA-binding regions" will be negatively selected during cancer evolution, while nonsynonymous mutation in "non HLA-binding regions" will not be negatively selected. This will lead to decreased nonsynonymous vs synonymous mutation ratio (n/s) in "HLA-binding regions" compared with "non HLA-binding regions". They defined HLA-binding mutation ratio (HBMR) as the ratio of n/s in "HLA-binding regions" to "non HLA-binding regions", and reported that HBMRs are close to 1 in different types of cancer after background corrections, meaning neoantigen depletion signals are not detectable in different types of cancer. The fundamental problem of their hypothesis lies in that the actual neoantigens with immunogenicity do not overlap with their defined "HLA-binding regions". Actually, most neoantigens with immunogenicity are not located in "HLA-binding regions", when dissimilarity between mutant and wild type peptide are considered. It is the neoantigen with immunogenicity, but not nonsynonymous mutation in their defined "HLA-binding regions" undergo immunoediting based negative selection. Thus the results reported in that study are fundamentally flawed, and at this current stage we could not draw a solid conclusion as to whether the neoantigen depletion signal exists or not.

genomics↗