Hong Zheng

Stanford University | SU · Stanford Center for Biomedical Informatics Research

Significance Host genetics, environmental factors, and EBV infection together contribute to nasopharyngeal carcinoma (NPC) development. A number of critical genetic and epigenetic events contributing to tumor development has been reported. However, the genomic alterations in NPC have not been completely deciphered. We used the whole-exome sequencin...

Significance Nasopharyngeal carcinoma (NPC) is a valuable cancer model to study the interaction of host genetics, viral infection, and environment in tumorigenesis. Little is known about the genetic basis for the remarkably distinct geographical distribution of NPC. We used a whole-exome sequencing approach to identify the genetic alterations assoc...

Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically...

RNA silencing, mediated by small RNAs including microRNAs (miRNAs) and small interfering RNAs (siRNAs), is a potent antiviral or antibacterial mechanism, besides regulating normal cellular gene expression critical for development and physiology. To gain insights into host small RNA metabolism under infections by different viruses, we used Solexa/Il...

Infection, autoimmunity, and cancer are principal human health challenges of the 21st century. Often regarded as distinct ends of the immunological spectrum, recent studies hint at potential overlap between these diseases. For example, inflammation can be pathogenic in infection and autoimmunity. T resident memory (TRM) cells can be beneficial in i...

Viral pandemics and epidemics pose a significant global threat. While macaque models of viral disease are routinely used, it remains unclear how conserved antiviral responses are between macaques and humans. Therefore, we conducted a cross-species analysis of transcriptomic data from over 6,088 blood samples from macaques and humans infected with o...

Viral pandemics and epidemics pose a significant global threat, with emerging and re-emerging viruses responsible for four pandemics in the 21st century alone. While macaques have been utilized as a model for understanding viral disease in a controlled setting, it remains unclear how conserved the antiviral responses to diverse viruses are between...

The human leukocyte antigen (HLA) locus plays a central role in adaptive immune function and has significant clinical implications for tissue transplant compatibility and allelic disease associations. Studies using bulk-cell RNA sequencing have demonstrated that HLA transcription may be regulated in an allele-specific manner and single-cell RNA seq...

Objective Recent observations in systemic juvenile idiopathic arthritis (JIA) suggest an increasing incidence of high‐mortality interstitial lung disease often characterized by a variant of pulmonary alveolar proteinosis (PAP). Co‐occurrence of macrophage activation syndrome (MAS) and PAP in systemic JIA suggests a shared pathology, but patients wi...

Sotos syndrome (SS), the most common overgrowth with intellectual disability (OGID) disorder, is caused by inactivating germline mutations of NSD1, which encodes a histone H3 lysine 36 methyltransferase. To understand how NSD1 inactivation deregulates transcription and DNA methylation (DNAm), and to explore how these abnormalities affect human deve...

Predicting the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for the severity of viral infections and validate it in independent data, including COVID-19. We developed a logistic regression-based classifier for the severity of viral infections and validated it in multi...

Background: Atypical tumor response patterns during immune checkpoint inhibitor therapy pose a challenge to clinicians and investigators in immuno-oncology practice. This study evaluated tumor burden dynamics to identify imaging biomarkers for treatment response and overall survival (OS) in advanced gastrointestinal malignancies treated with PD-1/...

Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruse...

Objectives: Recent observations in systemic Juvenile Idiopathic Arthritis (sJIA) suggest an increasing incidence of high-mortality interstitial lung disease (ILD), characterized pathologically by a variant of pulmonary alveolar proteinosis (PAP). The co-occurrence of macrophage activation syndrome (MAS) and PAP in sJIA suggested a shared pathology,...

RNA sequencing has emerged as a promising approach in cancer prognosis as sequencing data becomes more easily and affordably accessible. However, it remains challenging to build good predictive models especially when the sample size is limited and the number of features is high, which is a common situation in biomedical settings. To address these l...

Background Determining the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for the severity of viral infections and validate it in independent data, including COVID-19. Methods We developed the classifier for the severity of viral infections and validated it in multiple...

Brain tumors are the most common solid tumors affecting children, and its prognosis has been a great challenge for physicians and researchers. With the advances in high-throughput sequencing technology and digital pathology, more quantitative data is now becoming available and more information may potentially be discovered in whole slide images (WS...

DNA methylation is an important epigenetic mechanism regulating gene expression and its role in carcinogenesis has been extensively studied. High-throughput DNA methylation assays have been used broadly in cancer research. Histopathology images are commonly obtained in cancer treatment, given that tissue sampling remains the clinical gold-standard...

SARS-CoV-2 pandemic, the fourth pandemic of the decade, has underscored gaps in global pandemic preparedness and the need for generalizable tests to avert overwhelming healthcare systems worldwide, irrespective of a virus. We integrated 4,780 blood transcriptome profiles from patients infected with one of 16 viruses across 34 independent cohorts fr...

Background As missing values are frequently present in genomic data, practical methods to handle missing data are necessary for downstream analyses that require complete data sets. State-of-the-art imputation techniques, including methods based on singular value decomposition and K-nearest neighbors, can be computationally expensive for large data...

RNA sequencing has emerged as a promising approach in cancer prognosis as sequencing data becomes more easily and affordably accessible. However, it remains challenging to build good predictive models especially when the sample size is limited and the number of features is high, which is a common situation in biomedical settings. To address these l...

Background: Long non-coding RNAs (lncRNAs) are emerging as important regulators of various biological processes. While many studies have exploited public resources such as RNA sequencing (RNA-Seq) data in The Cancer Genome Atlas to study lncRNAs in cancer, it is crucial to choose the optimal method for accurate expression quantification. Results:...

The lack of representative nasopharyngeal carcinoma (NPC) models has seriously hampered research on EBV carcinogenesis and preclinical studies in NPC. Here we report the successful growth of five NPC patient-derived xenografts (PDXs) from fifty-eight attempts of transplantation of NPC specimens into NOD/SCID mice. The take rates for primary and rec...

Medical image biomarkers of cancer promise improvements in patient care through advances in precision medicine. Compared to genomic biomarkers, image biomarkers provide the advantages of being non-invasive, and characterizing a heterogeneous tumor in its entirety, as opposed to limited tissue available via biopsy. We developed a unique radiogenomic...

Motivation: The presence of missing values is a frequent problem encountered in genomic data analysis. Lost data can be an obstacle to downstream analyses that require complete data matrices. State-of-the-art imputation techniques including Singular Value Decomposition (SVD) and K-Nearest Neighbors (KNN) based methods usually achieve good performan...

Introduction Long non-coding RNAs (lncRNAs) emerge as important regulators of various biological processes. Many lncRNAs with tumor-suppressor or oncogenic functions in cancer have been discovered. While many studies have exploited public resources such as RNA-Seq data in The Cancer Genome Atlas (TCGA) to study lncRNAs in cancer, it is crucial to c...

Background: NPC has a striking geographical distribution. Hong Kong is one of the endemic regions in Southern China with incidence of 20 per 100,000 in males, 10 times higher than the rest of the world. NPC diagnosis usually occurs 20 years earlier than the other common cancers. Family clustering is often observed in both high- and low-risk regions...

Long non-coding RNAs (lncRNAs) emerge as important regulators of various biological processes. Many lncRNAs with tumor-suppressor or oncogenic functions in cancer have been discovered. While many studies have exploited public resources such as RNA-Seq data in The Cancer Genome Atlas (TCGA) to study lncRNAs in cancer, it is crucial to choose the opt...

Nasopharyngeal carcinoma (NPC) is a malignant tumor that emerges from the epithelium of the nasopharynx, the upper part of the throat behind the nose. It has remarkable ethnic and geographical distribution. It is extremely common in Southern China including Hong Kong. Multiple factors including host genetics, environmental factors, and Epstein-Barr...

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers due to a high frequency of metastasis. However, little is known about the genomic landscape of metastatic ESCC. To identify the genetic alterations that underlie ESCC metastasis, whole-exome sequencing (WES) was performed for 41 primary tumors and 15 lymph nodes (LNs) with...

Introduction Nasopharyngeal carcinoma (NPC) is a unique epithelial malignancy with a high prevalence in Southeast Asia. To date, the genomic abnormalities leading to the pathogenesis of NPC remain unclear. Thus, we sought to characterize the mutational landscape in NPC tumors using next-generation sequencing approaches and to identify significantly...

Nasopharyngeal carcinoma (NPC) is a unique epithelial malignancy that shows a remarkable geographical and ethic distribution. Multiple factors including predisposing genetic factors, environmental carcinogens, and Epstein-Barr virus (EBV) infection contribute to the accumulation of genetic and epigenetic alterations leading to NPC development. Emer...

Background: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy that originates in the nasopharynx. This cancer is highly prevalent in Asia, especially southern China. Familiar genetic predisposition is observed in 5-10% of NPC patients. It is well-accepted that host genetics, EBV infection, and environmental factors together contribute to N...

Background: Nasopharyngeal carcinoma (NPC) has the highest incidence in Guangdong province and Hong Kong in Southern China. Early detection of NPC is necessary to improve patient survival. Although aberrant methylation at promoter region of the tumour suppressors were often reported in NPC, genome-wide methylation changes have not been comprehensiv...

Viral pathogens are a major threat to rice production worldwide. Although RNA interference (RNAi) is known to mediate antiviral immunity in plant and animal models, the mechanism of antiviral RNAi in rice and other economically important crops is poorly understood. Here, we report that rice resistance to evolutionarily diverse viruses requires Argo...

RNA-dependent RNA polymerases (RDRs) from fungi, plants and some invertebrate animals play fundamental roles in antiviral defense. Here, we investigated the role of RDR6 in the defense of economically important rice plants against a negative-strand RNA virus (Rice stripe virus, RSV) that causes enormous crop damage. In three independent transgenic...