Quantitative and Longitudinal Assessment of Systemic Innate Immunity in Health and Disease Using a 2D Gene Model.

Dysregulation of innate immunity is deeply involved in infectious and autoimmune diseases. For a better understanding of pathogenesis and improved management of these diseases, it is of vital importance to implement convenient monitoring of systemic innate immunity. Built upon our previous works on the host transcriptional response to infection in peripheral blood, we proposed a 2D gene model for the simultaneous assessment of two major components of systemic innate immunity, including VirSig as the signature of the host response to viral infection and BacSig as the signature of the host response to bacterial infection.

Hypoxia and Activation of Neutrophil Degranulation-Related Genes in the Peripheral Blood of COVID-19 Patients.

Severe COVID-19 is characterized by systematic hyper-inflammation and subsequent damage to various organs. Therefore, it is critical to trace this cascade of hyper-inflammation. Blood transcriptome has been routinely utilized in the interrogation of host immune response in COVID-19 and other infectious conditions.

A two-gene marker for the two-tiered innate immune response in COVID-19 patients.

For coronavirus disease 2019 (COVID-19), a pandemic disease characterized by strong immune dysregulation in severe patients, convenient and efficient monitoring of the host immune response is critical. Human hosts respond to viral and bacterial infections in different ways, the former is characterized by the activation of interferon stimulated genes (ISGs) such as IFI27, while the latter is characterized by the activation of anti-bacterial associated genes (ABGs) such as S100A12. This two-tiered innate immune response has not been examined in COVID-19.

A single transcript for the prognosis of disease severity in COVID-19 patients.

With many countries strapped for medical resources due to the COVID-19 pandemic, it is highly desirable to allocate the precious resources to those who need them the most. Several markers have been found to be associated with the disease severity in COVID-19 patients. However, the established markers only display modest prognostic power individually and better markers are urgently needed.

A host-based two-gene model for the identification of bacterial infection in general clinical settings.

Objectives: In this study, we aimed to develop a simple gene model to identify bacterial infection, which can be implemented in general clinical settings.

Methods: We used a clinically availablereal-time quantitative polymerase chain reaction platform to conduct focused gene expression assays on clinical blood samples. Samples were collected from 2 tertiary hospitals.

Single-cell RNA-Seq revealed profound immune alteration in the peripheral blood of patients with bacterial infection.

Objectives: Bacterial infection remains one of the greatest threats to human health. However, how human hosts respond to bacterial infection has not been thoroughly understood. Better understanding of this response will improve human health.

Gene dysregulation in peripheral blood of moyamoya disease and comparison with other vascular disorders.

Objective: Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology, sharing many similar clinical symptoms with other vascular disorders. This study aimed to investigate gene dysregulation in peripheral blood of MMD and compare it with other vascular disorders.

Methods: Transcriptomic profiles of 12 MMD patients and 8 healthy controls were obtained using RNA sequencing.

Evaluation of Peripheral Immune Dysregulation in Alzheimer's Disease and Vascular Dementia.

Immune dysregulation has been observed in the brain and blood of patients with Alzheimer's disease (AD). However, a convenient assay to evaluate peripheral immune dysregulation in AD has not been developed, partly due to the inconsistent observations from different studies. We hypothesized that peripheral immune dysregulation may only exist in a subpopulation of AD patients; therefore it may be valuable to identify this subpopulation with a convenient assay.

The frontline of immune response in peripheral blood.

Peripheral blood is an attractive source for the discovery of disease biomarkers. Gene expression profiling of whole blood or its components has been widely conducted for various diseases. However, due to population heterogeneity and the dynamic nature of gene expression, certain biomarkers discovered from blood transcriptome studies could not be replicated in independent studies.

GSA: Genome Sequence Archive.

With the rapid development of sequencing technologies towards higher throughput and lower cost, sequence data are generated at an unprecedentedly explosive rate. To provide an efficient and easy-to-use platform for managing huge sequence data, here we present Genome Sequence Archive (GSA; http://bigd.big.

Towards Personalized Intervention for Alzheimer's Disease.

Alzheimer's disease (AD) remains to be a grand challenge for the international community despite over a century of exploration. A key factor likely accounting for such a situation is the vast heterogeneity in the disease etiology, which involves very complex and divergent pathways. Therefore, intervention strategies shall be tailored for subgroups of AD patients.

Perturbation of the transcriptome: implications of the innate immune system in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease with broad impact. Although Aβ and tau have been proposed as the key molecules in the disease mechanism, comprehensive understanding of AD pathogenesis requires a systemic view at the genomic level. From studies on the brain transcriptome of AD, we have gradually realized the contribution of the immune system to AD development.

Alzheimer's Disease: Genomics and Beyond.

Alzheimer's disease (AD) is a major form of senile dementia. Despite the critical roles of Aβ and tau in AD pathology, drugs targeting Aβ or tau have so far reached limited success. The advent of genomic technologies has made it possible to gain a more complete picture regarding the molecular network underlying the disease progression which may lead to discoveries of novel treatment targets.

Common Aging Signature in the Peripheral Blood of Vascular Dementia and Alzheimer's Disease.

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most dominant forms of dementia in elderly people. Due to the large overlap between AD and VaD in clinical observations, great controversies exist regarding the distinction and connection between these two types of senile dementia. Here for the first time, we resort to the gene expression pattern of the peripheral blood to compare AD and VaD objectively.

Web resources for stem cell research.

In this short review, we have presented a brief overview on major web resources relevant to stem cell research. To facilitate more efficient use of these resources, we have provided a preliminary rating based on our own user experience of the overall quality for each resource. We plan to update the information on an annual basis.

AlzBase: an Integrative Database for Gene Dysregulation in Alzheimer's Disease.

Alzheimer's disease (AD) affects a significant portion of elderly people worldwide. Although the amyloid-β (Aβ) cascade hypothesis has been the prevailing theory for the molecular mechanism of AD in the past few decades, treatment strategies targeting the Aβ cascade have not demonstrated effectiveness as yet. Thus, elucidating the spatial and temporal evolution of the molecular pathways in AD remains to be a daunting task.

Genomics in neurological disorders.

Neurological disorders comprise a variety of complex diseases in the central nervous system, which can be roughly classified as neurodegenerative diseases and psychiatric disorders. The basic and translational research of neurological disorders has been hindered by the difficulty in accessing the pathological center (i.e.

Hidden risk genes with high-order intragenic epistasis in Alzheimer's disease.

Meta-analysis of data from genome-wide association studies (GWAS) of Alzheimer's disease (AD) has confirmed the high risk of APOE and identified twenty other risk genes/loci with moderate effect size. However, many more risk genes/loci remain to be discovered to account for the missing heritability. The contributions from individual singe-nucleotide polymorphisms (SNPs) have been thoroughly examined in traditional GWAS data analysis, while SNP-SNP interactions can be explored by a variety of alternative approaches.

Distinctive RNA expression profiles in blood associated with Alzheimer disease after accounting for white matter hyperintensities.

Background: Defining the RNA transcriptome in Alzheimer Disease (AD) will help understand the disease mechanisms and provide biomarkers. Though the AD blood transcriptome has been studied, effects of white matter hyperintensities (WMH) were not considered. This study investigated the AD blood transcriptome and accounted for WMH.

Robust gene dysregulation in Alzheimer's disease brains.

The brain transcriptome of Alzheimer's disease (AD) reflects the prevailing disease mechanism at the gene expression level. However, thousands of genes have been reported to be dysregulated in AD brains in existing studies, and the consistency or discrepancy among these studies has not been thoroughly examined. Toward this end, we conducted a comprehensive survey of the brain transcriptome datasets for AD and other neurological diseases.

Conformational elasticity can facilitate TALE-DNA recognition.

Sequence-programmable transcription activator-like effector (TALE) proteins have emerged as a highly efficient tool for genome engineering. Recent crystal structures depict a transition between an open unbound solenoid and more compact DNA-bound solenoid formed by the 34 amino acid repeats. How TALEs switch conformation between these two forms without substantial energetic compensation, and how the repeat-variable di-residues (RVDs) discriminate between the cognate base and other bases still remain unclear.

Functional networking of human divergently paired genes (DPGs).

Divergently paired genes (DPGs), also known as bidirectional (head-to-head positioned) genes, are conserved across species and lineages, and thus deemed to be exceptional in genomic organization and functional regulation. Despite previous investigations on the features of their conservation and gene organization, the functional relationship among DPGs in a given species and lineage has not been thoroughly clarified. Here we report a network-based comprehensive analysis on human DPGs and our results indicate that the two members of the DPGs tend to participate in different biological processes while enforcing related functions as modules.

Chromosome 19p in Alzheimer's disease: when genome meets transcriptome.

Genetic studies have identified several genomic loci including chr19p13.2 relevant to Alzheimer's disease (AD) susceptibility. However, the functional roles of these genomic loci in AD pathogenesis require further clarification.

iBIG: an integrative network tool for supporting human disease mechanism studies.

Understanding the mechanism of complex human diseases is a major scientific challenge. Towards this end, we developed a web-based network tool named iBIG (stands for integrative BIoloGy), which incorporates a variety of information on gene interaction and regulation. The generated network can be annotated with various types of information and visualized directly online.