Junwen Wang

• PhD, UW-Seattle; MCIT, UPenn
• Professor at Mayo Clinic - Scottsdale

Background Hypomagnesemia has been correlated with inferior outcomes in patients with large B cell lymphoma (LBCL) undergoing stem cell transplants. As T-cell and myeloid cell dysfunction have been associated with low magnesium conditions, we investigated whether serum magnesium (Mg) levels could predict clinical outcomes in LBCL patients who recei...

Recipients’ age has emerged as a key factor that impacts on acute renal allograft rejection and graft survival. Age-related functional and structural changes in the immune system have been observed, yet the precise influence of aged immunity on kidney transplant remains unclear. In an initial retrospective analysis of clinical data gathered from tw...

The role of the bone marrow (BM) microenvironment in regulating the antitumor immune response in Waldenstrom macroglobulinemia (WM) remains poorly understood. Here we transcriptionally and phenotypically profiled non-malignant (CD19⁻ CD138⁻) BM cells from WM patients with a focus on myeloid derived suppressive cells (MDSCs) to provide a deeper unde...

Background Liver cancer remains the top death-related cancer type globally with limited treatment options for patients with unresectable hepatocellular carcinoma [HCC] and intrahepatic cholangiocarcinoma [iCCA].1–3 We hypothesize that combining the in-situ dendritic cell (DC) after external beam radiotherapy (EBRT) would enhance tumor-specific immu...

Background Hypomagnesemia has been correlated with inferior outcomes in patients with large B cell lymphoma (LBCL) undergoing stem cell transplants. As T-cell and myeloid cell dysfunction have been associated with low magnesium conditions, we investigated whether serum magnesium (Mg) levels could predict clinical outcomes in LBCL patients who recei...

The role of the bone marrow (BM) microenvironment in regulating the antitumor immune response in Waldenstrom macroglobulinemia (WM) remains limited. Here we transcriptionally and phenotypically profiled non-malignant (CD19 ⁻ CD138 ⁻ ) BM cells from WM patients with a focus on myeloid derived suppressive cells (MDSCs) to provide a deeper understandi...

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, inc...

T-lymphocytes are prevalent in the tumor microenvironment of follicular lymphoma (FL). However, the phenotype of T-cells may vary, and the prevalence of certain T-cell subsets may influence tumor biology and patient survival. We therefore analyzed a cohort of 82 FL patients using CyTOF to determine whether specific T-cell phenotypes were associated...

CCCTC-binding factor (CTCF) is a transcription regulator with a complex role in gene regulation. The recognition and effects of CTCF on DNA sequences, chromosome barriers, and enhancer blocking are not well understood. Existing computational tools struggle to assess the regulatory potential of CTCF-binding sites and their impact on chromatin loop f...

Background Alzheimer’s disease (AD) is the most common type of age-related dementia, affecting 6.2 million people aged 65 or older according to CDC data. It is commonly agreed that discovering an effective AD diagnosis biomarker could have enormous public health benefits, potentially preventing or delaying up to 40% of dementia cases. Tau neurofibr...

High grade glioma (HGG) represents a group of devastating diseases with dismal prognosis. Surgical resection of the contrast enhancing (CE) region of HGG remains the mainstay of treatment, but recurrence inevitably arises from the unresected non-contrast enhancing (NE) region, surgically inaccessible due to cancer cell invasion into healthy brain t...

Background: Alzheimer's Disease (AD) is the most common type of age-related dementia, affecting 6.2 million people aged 65 or older according to CDC data. It is commonly agreed that discovering an effective AD diagnosis biomarker could have enormous public health benefits, potentially preventing or delaying up to 40% of dementia cases. Tau neurofib...

Focal segmental glomerulosclerosis (FSGS) has an over 30% risk of recurrence after kidney transplantation (Ktx) and is associated with an extremely high risk of graft loss. However, mechanisms remain largely unclear. Thus, this study identifies novel genes related to the recurrence of FSGS (rFSGS). Whole genome-wide sequencing and next-generation R...

Predicting metal-binding sites in proteins is critical for understanding the protein’s biological function. Here, we develop an ensemble deep convolutional neural network (CNN) method for predicting metal-binding sites based on their three-dimensional (3D) structure. We build multi-channel 3D voxels based on biophysical characteristics obtained fro...

Understanding intra-tumor heterogeneity is critical for studying tumorigenesis and designing personalized treatments. To decompose the mixed cell population in a tumor, subclones are inferred computationally based on variant allele frequency (VAF) from bulk sequencing data. In this study, we showed that sequencing depth, mean VAF, and variance of V...

How CTCF recognizes insulators to exert chromosome barrier or enhancer blocking effects remains to be interrogated. Despite many computational tools were developed to predict CTCF-mediated loops qualitatively or quantitatively, few could specially evaluate the insulative potential of DNA sequence at CTCF binding sites (CBSs) and how it affects chro...

High-grade gliomas represent the most common type of primary adult malignant brain tumor historically diagnosed and graded from histologic criteria alone. Gliomas harboring isocitrate dehydrogenase (IDH) 1 or 2 mutations, which are present in more than 80% of World Health Organization (WHO) grade 2 or 3 tumors, portend a favorable prognosis as comp...

Glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median survival time of 12-15 months and 5-year survival rate of 5%. Despite the application of advanced genetics and biological breakthroughs in GBM, the outcome for GBM remains dismal. Previous genome-wide association studies (GWAS) for GBM shows that the incidence ra...

Purpose: Regulatory T cells (Tregs) are essential to T-cell homeostasis and modulate the anti-tumor immune response in lymphoma patients. However, the biology and prognostic impact of Tregs in splenic marginal zone lymphoma (SMZL) have not been studied. Experimental design: Biopsy specimens from 24 SMZL patients and 12 reactive spleens (rSP) fro...

OBJECTIVES/GOALS: The goal of this study is to evaluate the role of WNT5A and WNT5a-AS1 in sex-differences of GBM progression. In our preliminary studies, we found that a long non-coding RNA WNT5A-AS1 is overexpressed in male GBM patients. We also found that WNT5A-AS1s expression shows a negative correlation with overall survival within male patien...

Alzheimer's disease (AD) affects more than 1 in 9 people age 65 and older and becomes an urgent public health concern as the global population ages. Tau tangle is the specific protein pathological hallmark of AD and plays a crucial role in leading to dementia-related structural deformations observed in magnetic resonance imaging (MRI) scans. The vo...

Alzheimer's disease (AD) affects more than 1 in 9 people age 65 and older and becomes an urgent public health concern as the global population ages. In clinical practice, structural magnetic resonance imaging (sMRI) is the most accessible and widely used diagnostic imaging modality. Additionally, genome-wide association studies (GWAS) and transcrip...

Background Imaging, cognitive and fluid data have been widely studied to identify quantitative biomarkers that can help predict the status and progression of Alzheimer’s disease (AD). However, it is still an underexplored topic whether there exist subpopulations with different genetic profiles across which the biomarker‐based prediction models may...

Alzheimer's disease (AD) affects more than 1 in 9 people age 65 and older and becomes an urgent public health concern as the global population ages. In clinical practice, structural magnetic resonance imaging (sMRI) is the most accessible and widely used diagnostic imaging modality. Additionally, genome-wide association studies (GWAS) and transcrip...

Cell fate conversion by overexpressing defined factors is a powerful tool in regenerative medicine. However, identifying key factors for cell fate conversion requires laborious experimental efforts; thus, many of such conversions have not been achieved yet. Nevertheless, cell fate conversions found in many published studies were incomplete as the e...

Regulatory B cells (Bregs) contribute to immune regulation. However, the mechanisms of action of Bregs remain elusive. Here, we report that T cell immunoreceptor with Ig and ITIM domains (TIGIT) expressed on human memory B cells especially CD19 ⁺ CD24 hi CD27 ⁺ CD39 hi IgD ⁻ IgM ⁺ CD1c ⁺ B cells is essential for effective immune regulation. Mechani...

Radiogenomics uses machine-learning (ML) to directly connect the morphologic and physiological appearance of tumors on clinical imaging with underlying genomic features. Despite extensive growth in the area of radiogenomics across many cancers, and its potential role in advancing clinical decision making, no published studies have directly addresse...

The advances of large-scale genomics studies have enabled compilation of cell type-specific, genome-wide DNA functional elements at high resolution. With the growing volume of functional annotation data and sequencing variants, existing variant annotation algorithms lack the efficiency and scalability to process big genomic data, particularly when...

Disturbed intrauterine development increases the risk of renal disease. Various studies have reported that the Notch signalling plays a significant role in kidney development and kidney diseases. A disintegrin and metalloproteinase domain 10 (ADAM10), an upstream protease of Notch pathway, is also reportedly involved in renal fibrosis. However, how...

BACKGROUND: Radiogenomics uses machine-learning (ML) to directly connect the morphologic and physiological appearance of tumors on clinical imaging with underlying genomic features. Despite extensive growth in the area of radiogenomics across many cancers, and its potential role in advancing clinical decision making, no published studies have direc...

Background Disease progression prediction based on neuroimaging biomarkers is vital in Alzheimer’s disease (AD) research. Convolutional neural networks (CNN) have been proved to be powerful for various computer vision research by refining reliable and high-level feature maps from image patches. Objective A key challenge in applying CNN to neuroima...

TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a co-inhibitory receptor, highly expressed by Tregs, and contributes to the suppressive function of Tregs by limiting pro-inflammatory Th1 and Th17 cell responses. Herein, we report that subsets of human regulatory B cells (Bregs) express surface TIGIT and can thus play a critical role in im...

[This corrects the article DOI: 10.18632/oncotarget.18150.].

Motivation: Functions of cancer driver genes vary substantially across tissues and organs. Distinguishing passenger genes, oncogenes (OGs) and tumor-suppressor genes (TSGs) for each cancer type is critical for understanding tumor biology and identifying clinically actionable targets. Although many computational tools are available to predict putat...

Metalloproteins play important roles in many biological processes. Mutations at the metal-binding sites may functionally disrupt metalloproteins, initiating severe diseases; however, there seemed to be no effective approach to predict such mutations until now. Here we develop a deep learning approach to successfully predict disease-associated mutat...

In clinical cancer treatment, genomic alterations would often affect the response of patients to anticancer drugs. Studies have shown that molecular features of tumors could be biomarkers predictive of sensitivity or resistance to anticancer agents, but the identification of actionable mutations are often constrained by the incomplete understanding...

Understanding intratumor heterogeneity is critical to designing personalized treatments and improving clinical outcomes of cancers. Such investigations require accurate delineation of the subclonal composition of a tumor, which to date can only be reliably inferred from deep-sequencing data (>300x depth). To enable accurate subclonal discovery in t...

Functions of cancer driver genes depend on cellular contexts that vary substantially across tissues and organs. Distinguishing oncogenes (OGs) and tumor suppressor genes (TSGs) for each cancer type is critical to identifying clinically actionable targets. However, current resources for context-aware classifications of cancer drivers are limited. In...

We performed a comprehensive pan-cancer analysis in the Cancer Genomics Cloud of HTSeq-FPKM normalized protein coding mRNA data from 17 cancer projects in the Cancer Genome Atlas, these are Adrenal Gland, Bile Duct, Bladder, Brain, Breast, Cervix, Colorectal, Esophagus, Head and Neck, Kidney, Liver, Lung, Pancreas, Prostate, Stomach, Thyroid and Ut...

We present MetaMarker, a pipeline for discovering metagenomic biomarkers from WMS samples. Different from existing methods, MetaMarker is based on a de novo approach that does not require mapping raw reads to a reference database. We applied MetaMarker on WMS of colorectal cancer (CRC) stool samples from France to discover CRC specific metagenomic...

Background: Chromatin alterations are important mediators of gene expression changes. We have recently shown that activated non-canonical NF-κB signaling (RelB/p52) recruits histone acetyltransferase CBP and deacetylase HDAC1 to selectively acetylate H3K9 (H3K9ac) to induce expression of corticotropin-releasing hormone (CRH) and prostaglandin-endo...

Integration and analysis of high content omics data have been critical to the investigation of molecule interactions (e.g., DNA–protein, protein–protein, chemical–protein) in biological systems. Human proteomic strategies that provide enriched information on cell surface proteins can be utilized for repurposing of drug targets and discovery of dise...

Glioblastoma (GBM) is one of the most common, deadly, and difficult-to-treat adult brain tumors. Surgical removal of the tumor, followed by radiotherapy (RT) and temozolomide (TMZ) administration, is the current treatment modality, but this regimen only modestly improves overall patient survival. Invasion of cells into the surrounding healthy brain...

Aims: We propose a novel machine learning approach to expand the knowledge about drug-target interactions. Our method may help to develop effective, less harmful treatment strategies and to enable the detection of novel indications for existing drugs. Methods: We developed a novel machine learning strategy to predict drug-target interactions bas...

Lung cancer has the highest mortality across all cancers in the world. Epidermal growth factor receptor () is commonly mutated in lung adenocarcinomas from Asian non-smoking females. These tumors usually respond to tyrosine kinase inhibitors (-TKI), but the outcomes vary in different patients. Though T790M, amplification of MET and other mechanisms...

Genome-wide association studies have generated over thousands of susceptibility loci for many human complex traits, and yet for most of these associations the true causal variants remain unknown. Tissue/cell type-specific prediction and prioritization of non-coding regulatory variants will facilitate the identification of causal variants and underl...

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Background: Characterizing the binding preference of RNA-binding proteins (RBP) is essential for us to understand the interaction between an RBP and its RNA targets, and to decipher the mechanism of post-transcriptional regulation. Experimental methods have been used to generate protein-RNA binding data for a number of RBPs in vivo and in vitro. U...

AIM To determine the frequency and risk factors for colorectal cancer (CRC) development among individuals with resected advanced adenoma (AA)/traditional serrated adenoma (TSA)/advanced sessile serrated adenoma (ASSA). METHODS Data was collected from medical records of 14663 subjects found to have AA, TSA, or ASSA at screening or surveillance colo...

Traditional RNA sequencing (RNA-seq) allows the detection of gene expression variations between two or more cell populations through differentially expressed gene (DEG) analysis. However, genes that contribute to cell-to-cell differences are not discoverable with RNA-seq because RNA-seq samples are obtained from a mixture of cells. Single-cell RNA-...

The majority of colorectal cancer (CRC) arises from precursor lesions known as polyps. The molecular determinants that distinguish benign from malignant polyps remain unclear. To molecularly characterize polyps, we utilized Cancer Adjacent Polyp (CAP) and Cancer Free Polyp (CFP) patients. CAPs had tissues from the residual polyp of origin and conti...

Aims: MicroRNAs (miRNAs) are crucial for the post-transcriptional control of protein-encoding genes, and together with transcription factors (TFs) regulate gene expression; however, the regulatory activities of miRNAs during cardiac development are only partially understood. In this study, we tested the hypothesis that integrative computational ap...

Urease as a potential target of antimicrobial drugs has received considerable attention given its versatile roles in microbial infection. Development of effective urease inhibitors, however, is a significant challenge due to the deeply buried active site and highly specific substrate of a bacterial urease. Conventionally, urease inhibitors are desi...

Normalized urease and GTPase activity of E. coli cells expressing the completed urease gene. The ureG gene (plasmid pET32a-ureG) was complemented to E. coli cells harboring plasmid pHP8080ΔG; the expression of ureG gene was induced by 100 μM IPTG. After growth, with the addition of gradient amounts of CBS in cultured medium, the GTPase and ureolyti...

UV-vis spectra of proteins with or without addition of BiNTA. (A) UreE, (B) UreFH complex, (C) UreG-C48A, (D) UreG-C66A, and (E) UreG-C48C66A. The peaks at approximately 340 nm and approximately 360 nm indicated Bi(III) binding to Cys66 and Cys48 (in UreG-C48A and UreG-C66A), respectively (C, D). the shift of absorption peaks may be due to the diff...

Interplay between Bi(III) and Ni(II) binding to UreG. Given the critical role of GTP and Mg(II) in Ni-binding of UreG, UV spectroscopic studies were carried out in HEPES buffer containing 100 μM GTP and 1 mM MgSO4. (A) UV spectra of Bi-UreG upon addition of zero to two molar equivalents of Ni(II) ions. (B) UV spectra of Ni-UreG upon incubation with...

Effect of Bi(III) on UreG dimer and UreE-UreG complexes by gel filtration chromatography. (A) Oligomeric states of Ni-UreG with (red curve) or without (black curve) two molar equivalents of Bi(III) treatment in the presence of KHCO3 (1 mM). (B) Oligomeric states of UreE-UreG complex (2E-2G) with (red curve) or without (green curve) molar equivalent...

Comparison of inhibition of urease by CBS and AHA in different bacteria. AHA exerts only moderate inhibitory activity against urease with IC50 values at around mM levels, whereas CBS exhibits more potent efficiency on anti-urease activity in bacteria cells. For convenient comparison, the activities of urease in the samples without CBS/AHA treatment...

(A) Fluorescence spectra of cmpd4 (B) Titration of cmpd4 produced FRET between UreG and cmpd4. When the mixture of UreG and cmpd4 was excited at 280 nm, the emission intensity at 410 nm (FLUreG+cmpd4, as shown in Fig 4) consisted of two components: the direct emission of cmpd4 and the emission of cmpd4 excited by energy transferred from UreG. There...

Representative binding curve of GTP to UreG protein. The dissociation constant of GTP to apo-UreG was determined to be ca. 65 μM, consitent with the previous report that apo-UreG does poorly at GTP-binding. The underlying data can be found in S1 Data. (PNG)

Ni content of H. pylori cells with the addition of Bi as CBS in cultured medium. H. pylori was cultured with or without supplementation of Bi(III) to medium. After harvest and washing, the Ni content of H. pylori cells was determined by ICP-MS sequentially. For convenient comparison, the Ni contents in the samples without CBS treatment were set as...

Excitation (blue) and emission (red) spectra of cmpd4 (A) and cmpd8 (B). cmpd4 (100 μM) showed λex = 250, 280, 310 nm and λem = 410 nm, whereas the excitation maxium of cmpd8 (20 μM) was observed at 257 nm and emission maximum at 440 nm. cmpd8 exhibited little excitation at 280 nm; thus, only UreG and cmpd4 have significant fluorescent signals with...

Surface representation showing guanine nucleotide binding pocket of UreG. (A) GDP (PDB: 2HI0), (B) cmpd4, and (C) cmpd8. The G1 (P-loop) motif is in magenta, and residues K146 and R179 of UreG are in red, which provide potential hydrophobic interaction with compounds. (PNG)

Gel filtration profiles of protein UreGΔNKXD with or without GTPγs. UreG recognizes GTP using the canonical NKXD motif (G4) and is likely to form UreG dimer upon Ni and GTP binding. To examine the effect of the triple mutagenesis (N145A/K146A/D148A) on GTP binding of UreG, UreGΔNKXD (10 μM) was incubated with or without GTPγs (30 μM) in HEPES buffe...

Representative binding curves of cmpd4 and cmpd8 to UreGΔNKXD. The mutant exhibits lower binding affinity (3 to 4 folds) towards cmpd4/cmpd8 compared to the wild-type UreG. The underlying data can be found in S1 Data. (PNG)

List of primers for plasmid construction. The mutation sites are indicated in red. (DOCX)

Gel filtration profiles of UreE with or without Bi(III). Apo-UreE was eluted at approximately 13.5 ml corresponding to its dimeric form. Incubation with three molar equivalents of Bi(III) has little effect on the UreE dimer. (PNG)

Nickel-dependent GTPase UreG is conserved in various bacteria. Chaperone UreI, which is not required for urease maturation, has not been illustrated in the figure. (PNG)

The structures of the 11 representative hits from the virtual screening (cmpd1–cmpd11). (PNG)

GTPase assay and urease assay for validation of compounds from virtual screening. (A) GTPase activity of purified Ni-UreG (5 μM) in the presence of 20 μM small compounds. cmpd7 resulted in serious precipitation in the reaction, which led to the high absorption at 620 nm and false high activity. (B) urease activity of H. pylori cells with the supple...

Thermal shift assay to confirm binding of cmpd4 and cmpd8 to UreG. cmpd1, an inactive molecule, was used as a negative control. The underlying data can be found in S1 Data. (PNG)

UV-vis spectra of UreG with cmpd4 (A), and cmpd8 (B). Both cmpd4 and cmpd8 (100 μM) alone or in the presence of UreG (1 μM) gave rise to intense absorbance at around 280 nm, whereas the spectra of cmpd4/8-UreG mixture obtained after subtracting the spectra of cmpd4/8 are similar to those of UreG, indicating the presence of cmpd4/8 has negligible ef...

Effect of cmpd4 and cmpd8 on nickel binding property of UreG. UreG (5 μM) in HEPES buffer (5 μM GTP, 1 mM MgSO4) was titrated with NiSO4 in the presence of cmpd4 or cmpd8 at various concentrations. Titration of nickel ion into UreG samples led to the increasing of absorption at 337 nm, the highest of which was set as 100% for the percentage of Ni-b...

Effect of AHA, CBS, cmpd4 and cmpd8 on the survival of AGS with H. pylori infection. AHA, CBS, cmpd4, and cmpd8 (10 μM) were administrated to AGS cells with H. pylori infection. AHA showed little effect on inhibition of activity of H. pylori; CBS could protect AGS from cytotoxicity of H. pylori. As expected, low viability of AGS with the supplement...

Background Illumina paired-end sequencing has been increasingly popular for 16S rRNA gene-based microbiota profiling. It provides higher phylogenetic resolution than single-end reads due to a longer read length. However, the reverse read (R2) often has significant low base quality and a large proportion of R2s will be discarded after quality contro...

Background/aims: Infection with Acinetobacter baumannii was emerging as one of the leading causes of mortality after donation after cardiac death transpalantion. Methods: We reported a case of a recipient who underwent DCD renal transplantation and later got infected by A.baumannii. Etests were done to verify the susceptibility test results in c...

Long non-coding RNA (lncRNA) is a large class of gene transcripts with regulatory functions discovered in recent years. Many more are expected to be revealed with accumulation of RNA-seq data from diverse types of normal and diseased tissues. However, discovering novel lncRNAs and accurately quantifying known lncRNAs is not trivial from massive RNA...