Jin Chen

MOTIVATION: The majority of variation identified by genome wide association studies falls in non-coding genomic regions and is hypothesized to impact regulatory elements that modulate gene expression. Here we present a statistically rigorous software tool GREGOR (Genomic Regulatory Elements and Gwas Overlap algoRithm) for evaluating enrichment of any set of genetic variants with any set of regulatory features. Using variants from five phenotypes, we describe a data-driven approach to determine the tissue and cell types most relevant to a trait of interest and to identify the subset of regulatory features likely impacted by these variants. Last, we experimentally evaluate six predicted functional variants at six lipid-associated loci and demonstrate significant evidence for allele-specific impact on expression levels. GREGOR systematically evaluates enrichment of genetic variation with the vast collection of regulatory data available to explore novel biological mechanisms of disease and guide us toward the functional variant at trait-associated loci. AVAILABILITY AND IMPLEMENTATION: GREGOR, including source code, documentation, examples, and executables, is available at http://genome.sph.umich.edu/wiki/GREGOR. CONTACT: cristen@umich.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Abstract NP 105–113 -B*07:02-specific CD8 + T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP 105–113 -B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP 105–113 -B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP 105–113 -B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP 105–113 -B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

BACKGROUND: More than 2 months have passed since the novel coronavirus disease 2019 (COVID-19) first emerged in Wuhan, China. With the migration of people, the epidemic has rapidly spread within China and throughout the world. Due to the severity of the epidemic, undiscovered transmission of COVID-19 deserves further investigation. The aim of our study hypothesized possible modes of SARS-CoV-2 transmission and how the virus may have spread between two family clusters within a residential building in Guangzhou, China. METHODS: In a cross-sectional study, we monitored and traced confirmed patients and their close contacts from January 11 to February 5, 2020 in Guangzhou, China, including 2 family cluster cases and 61 residents within one residential building. The environmental samples of the building and the throat swabs from the patients and from their related individuals were collected for SARS-CoV-2 and tested with real-time reverse transcriptase polymerase chain reaction (RT-PCR). The relevant information was collected and reported using big data tools. RESULTS: There were two notable family cluster cases in Guangzhou, which included 3 confirmed patients (family No.1: patient A, B, C) and 2 confirmed patients (family No.2: patient D, E), respectively. None of patients had contact with other confirmed patients before the onset of symptoms, and only patient A and patient B made a short stop in Wuhan by train. Home environment inspection results showed that the door handle of family No.1 was positive of SARS-CoV-2. The close contacts of the 5 patients all tested negative of SARS-CoV-2 and in good health, and therefore were released after the official medical observation period of 14-days. Finally, according to the traceability investigation through applying big data analysis, we found an epidemiological association between family No.1 and family No.2, in which patient D (family No.2) was infected through touching an elevator button contaminated by snot with virus from patient A (family No.1) on the same day. CONCLUSIONS: Contaminants with virus from confirmed patients can pollute the environment of public places, and the virus can survive on the surface of objects for a short period of time. Therefore, in addition to the conventional droplet transmission, there is also indirect contact transmission such as snot-oral transmission that plays a crucial role in community spread of the virus.

Hepatocellular carcinoma (HCC) is the sixth-most common cancer and the third leading cause of cancer-related death in the world. However, 40-70% patients eventually suffer from postoperative recurrence within 5 years. HCC recurrence after surgery severely affects prognosis of the patients. Nevertheless, there is an opportunity to improve patients' prognosis if doctors and researchers can recognize the importance of a standardized perioperative management and study it in clinical and pre-clinical settings. Hence, based on our own experience and published studies from other researchers, we develop this consensus regarding multidisciplinary management of locally recurrent and metastatic hepatocellular carcinoma after resection. This consensus consists of the entire course of recurrent hepatocellular carcinoma (RHCC) management, including prediction of recurrence, prevention, diagnosis, treatment and surveillance of RHCC. Consensus recommendations are presented with grades of evidences (Ia, Ib, IIa, IIb, III and IV), and strength of recommendations (A, B, C, D and E). We also develop a decision-making path for RHCC treatment, which can intuitively demonstrate the management for RHCC. It is hoped that we may make some effort to standardize the management of RHCC and ultimately understand how to improve outcomes.

BACKGROUND AND AIMS: Observational epidemiology studies suggested a relationship between the gut microbiome and primary liver cancer. However, the causal relationship remains unclear because of confounding factors and reverse causality. We aimed to explore the causal role of the gut microbiome in the development of primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: Mendelian randomization (MR) study was conducted using summary statistics from genome-wide association studies (GWAS) of the gut microbiome and liver cancer, and sequencing data from a case-control study validated the findings. A 5-cohort GWAS study in Germany (N = 8956) served as exposure, whilst the UK biobank GWAS study (N = 456 348) served as an outcome. The case-control study was conducted at the First Affiliated Hospital of Wenzhou Medical University from December 2018 to October 2020 and included 184 HCC patients, 63 ICC patients and 40 healthy controls. RESULTS: A total of 57 features were available for MR analysis, and protective causal associations were identified for Family_Ruminococcaceae (OR = 0.46 [95% CI, 0.26-0.82]; p = .009) and Genus_Porphyromonadaceae (OR = 0.59 [95% CI, 0.42-0.83]; p = .003) with HCC, and for Family_Porphyromonadaceae (OR = 0.36 [95% CI, 0.14-0.94]; p = .036) and Genus_Bacteroidetes (OR = 0.55 [95% CI, 0.34-0.90]; p = .017) with ICC respectively. The case-control study results showed that the healthy controls had a higher relative abundance of Family_Ruminococcaceae (p = .00033), Family_Porphyromonadaceae (p = .0055) and Genus_Bacteroidetes (p = .021) than the liver cancer patients. CONCLUSIONS: This study demonstrates that Ruminococcaceae, Porphyromonadaceae and Bacteroidetes are related to a reduced risk of liver cancer (HCC or ICC), suggesting potential significance for the prevention and control of liver cancer.