Han, Z.-g. | Search bioRxiv

bioRxiv2019

Single-Cell RNA-Seq Reveals Naïve B cells Associated with Better Prognosis of HCC

Hepatocellular Carcinoma (HCC) is a type of malignant solid tumor, causing high morbidity and mortality around the world and the major portion of HCC patients is from China. Cancer immunotherapies have shown some clinical responses in treating some types of cancer but did not shown significant efficiency in HCC treatment. This in part due to the impact of immune cells in the tumor microenvironment. It is commonly believed that HCC is a heterogeneous solid tumor and the microenvironment of HCC plays an important role in tumorgenesis and development. Currently, the residents of the microenvironment of HCC is not well-defined and clarification, especially the immune cells, which we believe that paly pivotal roles in tumorgenesis and development. To depict the landscape of the composition, lineage and functional states of the immune cells in HCC, we performed single-cell RNA sequencing on Diethylnitrosamine (DEN)-induced mouse HCC model. We observed heterogeneity within the immune and hepatocytes both in the precancerous condition of tumorigenesis and cancerous condition of HCC. In this study we found that the disease-associated changes appeared early in pathological progression and were highly cell-type specific. Specific subsets of T and B cells preferentially enriched in HCC, and we identified signature genes for each subset. Additionally, we mapped this group of specific cells to the human TCGA database. We found a cluster of naive B cells characterized by high expression of CD38 associated with better prognosis of human HCC. Our study demonstrates signaling interaction map based on receptor-ligand bonding on the single-cell level could broaden our comprehending of cellular networks in varies status. Our finding provides a new approach for patient stratification and will help further understand the functional states, dynamics and signaling interaction of B cells in hepatocellular carcinoma, and may provide a novel insight and therapeutics for the HCC.

cancer biology↗

bioRxiv2019

A Novel Neoantigen Discovery Approach based on Chromatin High Order Conformation: Mapping the Neoantigen to 3D Genome

The high-throughput sequencing technology has yielded reliable and ultra-fast sequencing for DNA and RNA. For tumor cells of cancer patients, when combining the results of DNA and RNA sequencing, one can identify potential neoantigens that stimulate immune response of the T cells. However, when the somatic mutations are abundant, it is computationally challenging to efficiently prioritize the identified neoantigen candidates according to their ability of activating the T cell immuno-response. Numerous prioritization or prediction approaches have been proposed to address this issue but none of them considers the original DNA loci of the neoantigens from the perspective of 3D genome. Here we retrospect the DNA origins of the immune-positive and non-negative neoantigens in the context of 3D genome and discovered that 1) DNA loci of the immuno-positive neoantigens tend to cluster genome-wise. 2) DNA loci of the immuno-positive neoantigens tend to belong to active chromosomal compartment (compartment A) in some chromosomes. 3). DNA loci of the immuno-positive neoantigens tend to locate at specific regions in the 3D genome. We believe that the 3D genome information will help more precise neoantigen prioritization and discovery and eventually benefit precision and personalized medicine in cancer immunotherapy.

bioinformatics↗