Yang Dai

• Ph.D
• Professor at University of Illinois Chicago

Accurate prediction of the host phenotype from a metagenomic sample and identification of the associated microbial markers are important in understanding potential host-microbiome interactions related to disease initiation and progression. We introduce PopPhy-CNN, a novel convolutional neural network (CNN) learning framework that effectively exploi...

The microbiome of the human body has been shown to have profound effects on physiological regulation and disease pathogenesis. However, association analysis based on statistical modeling of microbiome data has continued to be a challenge due to inherent noise, complexity of the data, and high cost of collecting large number of samples. To address t...

The advance in microbiome and metabolome studies has generated rich omics data revealing the involvement of the microbial community in host disease pathogenesis through interactions with their host at a metabolic level. However, the computational tools to uncover these relationships are just emerging. Here, we present MiMeNet, a neural network fram...

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful experimental approach to study cellular heterogeneity. One of the challenges in scRNA-seq data analysis is integrating different types of biological data to consistently recognize discrete biological functions and regulatory mechanisms of cells, such as transcription factor activities...

Gene expression is regulated at both transcriptional and post-transcriptional levels. DNA sequence and epigenetic modifications are key factors which regulate gene transcription. Understanding their complex interactions and their respective contributions to gene expression regulation remains a challenge in biological studies. We have developed iSEG...

Senescent cells accumulate in most tissues with organismal aging, exposure to stressors, or disease progression. It is challenging to identify senescent cells because cellular senescence signatures and phenotypes vary widely across distinct cell types and tissues. Here we developed an analytical algorithm that defines cell-type-specific and univers...

Uterine fibroids (UFs) are the most common non-cutaneous tumors in women worldwide. UFs arise from genetic alterations in myometrial stem cells (MM SCs) that trigger their transformation into tumor-initiating cells (UF SCs). Mutations in the RNA polymerase II Mediator subunit MED12 are dominant drivers of UFs, accounting for 70% of these clinically...

Fibrosis of the lower abdominal muscle (LAM) contributes to muscle weakening and inguinal hernia formation, an ailment affecting a noteworthy fifty percent of men by age 75, necessitating surgical correction as the singular therapy. Despite its prevalence, the mechanisms driving LAM fibrosis and hernia development remain poorly understood. Utilizin...

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with lung metastases being the most common site of distant spread and significantly worsening prognosis. Despite the growing availability of clinical and demographic data, predictive models for lung metastasis in HCC remain limited in scope and clinical applicability. In...

Because large brains are energetically expensive, they are associated with metabolic traits that facilitate energy availability across vertebrates. However, the biological underpinnings driving these traits are not known. Given its role in regulating host metabolism in disease studies, we hypothesized that the gut microbiome contributes to variatio...

Objective This cross-sectional study aims to assess the associations between serum leptin, adiponectin, leptin-to-adiponectin ratio (L/A ratio), and metabolic syndrome (MS) and HOMA-IR in five African-origin populations: Ghana, South Africa, Jamaica, Seychelles, and US. Methods Clinical measures included serum glucose, insulin, adipokines, blood p...

Exposure to toxic metals impacts obesity and type 2 diabetes (T2DM) risk. Yet, the underlying mechanisms remain largely unknown. Gut microbiota has been strongly associated with progression of cardiometabolic risk. To determine whether high metal exposures and gut dysbiosis interact to promote metabolic dysregulation and cardiometabolic risk, we as...

Importance Lung cancer disparities occur across minorities, namely Black populations, who face increased risks yet are screened at lower rates. Standards set by the United States Preventive Services Task Force (USPSTF) are derived from a predominantly White cohort: the National Lung Cancer Screening Trial (NLST), which exacerbates disparities in lu...

Disclosure: J. Jorgensen: None. C. Choo-Kang: None. L. Issa: None. J.A. Gilbert: None. G. Ecklu-Mensah: None. A. Luke: None. K. Bedu-Addo: None. T. Forrester: None. P. Bovet: None. E.V. Lambert: None. D. Rae: None. M. Argos: None. Y. Dai: None. R.M. Sargis: None. L.R. Dugas: None. B.T. Layden: None. Obesity is associated with an increased risk for...

Uterine fibroids (UFs) are the most common non-cutaneous tumors in women worldwide. UFs arise from genetic alterations in myometrial stem cells (MM SCs) that trigger their transformation into tumor initiating cells (UF SCs). Mutations in the RNA polymerase II Mediator subunit MED12 are dominant drivers of UFs, accounting for 70% of these clinically...

Since its introduction, generative artificial intelligence (AI) has seamlessly integrated into everyday life and dramatically changed our workflows. With its growing presence, it has become increasingly important to explore the full extent of its capabilities to ensure responsible use. While previous research has investigated generative AI’s abilit...

Background Perinatal depression is one of the most common medical complications during pregnancy and postpartum period, affecting 10% to 20% of pregnant individuals, with higher rates among Black and Latina women who are also less likely to be diagnosed and treated. Machine learning (ML) models based on electronic medical records (EMRs) have effect...

Monocytes and macrophages (Mos/Mϕs) play diverse roles in wound healing by adopting a spectrum of functional phenotypes; however, the regulation of such heterogeneity remains poorly defined. We enhanced our previously published Bayesian inference TF activity model, incorporating both single-cell RNA sequencing and single-cell ATAC sequencing data t...

Purpose of review This review evaluates the current knowledge of gut microbiome alterations in acute pancreatitis, including those that can increase acute pancreatitis risk or worsen disease severity, and the mechanisms of gut microbiome driven injury in acute pancreatitis. Recent findings Recent observational studies in humans showed the associat...

Background: Skeletal muscle fibrosis represents accumulation of extracellular matrix (ECM), often leading to muscle weakness and atrophy. Notably, lower abdominal muscle (LAM) fibrosis and atrophy cause inguinal herniation—a prevalent condition lacking pharmacological treatment. We developed a herniation mouse model, Arom hum , characterized by spo...

Uterine leiomyosarcoma (LMS) is a deadly uterine smooth muscle tumor. Leiomyoma with bizarre nuclei (LM-BN) and fumarate hydratase-deficient leiomyoma (FH-LM) are benign uterine smooth muscle tumors with remarkable nuclear atypia. FH-LM is driven by biallelic inactivation of fumarate hydratase, but the pathogenesis of LMS and LM-BN remains largely...

Disclosure: A. Zuberi: None. Y. Huang: None. A. Dotts: None. H. Wei: None. J. Coon V: None. T. Lizuka: None. O. Wu: None. O. Sotos: None. D. Chakravarti: None. Y. Dai: None. S.E. Bulun: None. P. Yin: None. A.Z. and Y.H. contributed equally to this work.† Y.D., S.E.B., and P.Y. are co-senior authors. ‡To whom correspondence should be addressed: Serd...

Disclosure: J. Jorgensen: None. C. Choo-Kang: None. G. Ecklu-Mensah: None. J. Gilbert: None. A. Luke: None. K. Bedu-Addo: None. T.E. Forrester: None. P. Bovet: None. E.V. Lambert: None. D. Rae: None. L. Dugas: None. Y. Dai: None. B.T. Layden: None. Obesity is a global public health crisis, which since 1975 has tripled world-wide. Concomitantly, obe...

Senescent cells accumulate in tissues with organismal age and contribute causally to multiple chronic diseases. In vivo senescent cell phenotypes are heterogeneous because cellular context and stressors vary by cell type and tissue. Due to the variability of senescence programs, there is no universal method to identify senescent cells and even wide...

Uterine leiomyomas cause heavy menstrual bleeding, anemia, and pregnancy loss in approximately 10 million US women. Driver mutations in the transcriptional mediator complex subunit 12 (MED12) gene in uterine myometrial cells initiate 70% of leiomyoma that grow in a progesterone-dependent manner. We showed a distinct chromatin occupancy landscape of...

Perinatal depression (PND) is one of the most common medical complications during pregnancy and postpartum period, affecting 10-20% of pregnant individuals. Black and Latina women have higher rates of PND, yet they are less likely to be diagnosed and receive treatment. Machine learning (ML) models based on Electronic Medical Records (EMRs) have bee...

Introduction: Diet and decreased gut microbiome diversity has been associated with acute pancreatitis (AP) risk. However, differences in dietary intake, gut microbiome and their impact on microbial end-metabolites have not been studied in AP. We aimed to determine differences in i) dietary intake ii) gut microbiome diversity and sulfidogenic bacte...

Mesenchymal stem cell (MSCs)-derived extracellular vesicles (EVs) are emerging therapeutic tools. Hypoxic pre-conditioning (HPC) of MSCs altered the production of microRNAs (miRNAs) in EVs, and enhanced the cytoprotective, anti-inflammatory, and neuroprotective properties of their derivative EVs in retinal cells. EV miRNAs were identified as the pr...

Pregnancy is a dynamic state with multiple metabolic changes occurring including insulin resistance. Gestational diabetes mellitus (GDM), a form of diabetes that appears during pregnancy, develops if metabolic aberrations occur, in particular, in normal pregnancy-induced insulin resistance. Multi-omics is a powerful approach for uncovering the mech...

Single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) assesses genome-wide chromatin accessibility in thousands of cells to reveal regulatory landscapes in high resolutions. However, the analysis presents challenges due to the high dimensionality and sparsity of the data. Several methods have been developed, including trans...

Single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) assesses genome-wide chromatin accessibility in thousands of cells to reveal regulatory landscapes in high resolutions. However, the analysis presents challenges due to the high dimensionality and sparsity of the data. Several methods have been developed, including trans...

Host-microbiome interactions are known to have substantial effects on human health, but the diversity of the human microbiome makes it difficult to definitively attribute specific microbiome features to a host phenotype. One approach to overcoming this challenge is to use animal models of host-microbiome interaction, but it must be determined that...

STUDY QUESTION What are the cellular composition and single-cell transcriptomic differences between myometrium and leiomyomas as defined by single-cell RNA sequencing? SUMMARY ANSWER We discovered cellular heterogeneity in smooth muscle cells (SMCs), fibroblast and endothelial cell populations in both myometrium and leiomyoma tissues. WHAT IS KNO...

The alterations in myometrial biology during labor are not well understood. The myometrium is the contractile portion of the uterus and contributes to labor, a process that may be regulated by the steroid hormone progesterone. Thus, human myometrial tissues from term pregnant in-active-labor (TIL) and term pregnant not-in-labor (TNIL) subjects were...

Studies have demonstrated the phenotypic heterogeneity of vascular endothelial cells (ECs) within a vascular bed; however, little is known about how distinct endothelial subpopulations in a particular organ respond to an inflammatory stimulus. We performed single cell RNA-sequencing of 35,973 lung ECs obtained during the baseline state as well as p...

Studying temporal gene expression shifts during disease progression provides important insights into the biological mechanisms that distinguish adaptive and maladaptive responses. Existing tools for the analysis of time course transcriptomic data are not designed to optimally identify distinct temporal patterns when analyzing dynamic differentially...

Background and aims Normal gestation involves reprogramming of maternal gut microbiome (GM) that contributes to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of GM – maternal metabolism interaction. Methods The GM and plasma metabolome of CD1, NIH-Swiss and C57 mice were analyzed usi...

Uterine leiomyoma (LM) is the most common tumor in women. Via its receptor (PGR) expressed in differentiated LM cells, progesterone stimulates paracrine signaling that induces proliferation of PGR-deficient LM stem cells (LSCs). Antiprogestins shrink LM but tumors regrow after treatment cessation possibly due to persisting LSCs. Using sorted primar...

The concurrent profiles of the gut microbiome and metabolome can be used in the diagnosis of complex diseases. However, the establishment of robust predictive models is challenging due to the high dimensionality of data and complex interactions among microbiome, metabolites, and host. Using deep neural networks consisting of an autoencoder for extr...

Background and aims: Normal gestation involves reprogramming of maternal gut microbiome (GM) that may contribute to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of GM maternal metabolism interaction. Methods: The GM and plasma metabolome of CD1, NIH Swiss and C57BL/6J mice were analy...

A recent analysis of endothelial cell (EC) gene expression suggests that ECs of distinct organs vary in their gene expression profiles and respond distinctly to the systemic inflammatory stimulus of endotoxemia (Jambusaria et al., 2020). There is a need to systematically define tissue-specific gene expression dynamics in response to inflammation bu...

Metagenomic studies of the microbiome community have revealed associations of the microbiome community to host disease state. The detection of these associations can rely on statistical analyses identifying differentially abundant taxa between diseased and healthy populations. Accurate prediction of the host phenotype from a metagenomic sample and...

The advance of metagenomic studies provides the opportunity to identify microbial taxa that are associated with human diseases. Multiple methods exist for the association analysis. However, the results could be inconsistent, presenting challenges in interpreting the host-microbiome interactions. To address this issue, we develop Meta-Signer, a nove...

The advance in microbiome and metabolome studies has generated rich omics data revealing the involvement of the microbial community in host disease pathogenesis through interactions with their host at a metabolic level. However, the computational tools to uncover these relationships are just emerging. Here, we present MiMeNet, a neural network fram...

Uterine leiomyoma is the most common tumor in women and can cause severe morbidity. Leiomyoma growth requires maintenance and proliferation of a stem cell population. Dysregulated DNA methylation has been reported in leiomyoma, but its role in leiomyoma stem cell regulation remains unclear. Here, we FACS sorted cells from human leiomyoma tissues in...

Accurate prediction of the host phenotypes from a microbial sample and identification of the associated microbial markers are important in understanding the impact of the microbiome on the pathogenesis and progression of various diseases within the host. A deep learning tool, PopPhy-CNN, has been developed for the task of predicting host phenotypes...

Background: The advance of metagenomic studies provides the opportunity to identify microbial taxa that are associated with human diseases. Multiple methods exist for the association analysis. However, the results could be inconsistent, presenting challenges in interpreting the host-microbiome interactions. To address this issue, we introduce Meta-...

Microbiota derived metabolites act as chemical messengers that elicit a profound impact on host physiology. Vitamin D receptor (VDR) is a key genetic factor for shaping the host microbiome. However, it remains unclear how microbial metabolites are altered in the absence of VDR. We investigated metabolites from mice with tissue-specific deletion of...

Blood vessels are lined by endothelial cells engaged in distinct organ-specific functions but little is known about their characteristic gene expression profiles. RNA-Sequencing of the brain, lung, and heart endothelial translatome identified specific pathways, transporters and cell-surface markers expressed in the endothelium of each organ, which...

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that di↵erences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 di↵e...

Oral mucosal wounds heal faster than skin wounds, yet the role of microRNAs in this differential healing has never been examined. To delineate the role of microRNAs in this site-specific injury response, we first compared the microRNAome of uninjured skin and oral mucosa in mice. A total of 53 tissue-specific microRNAs for skin and oral mucosa epit...

Food allergy is usually difficult to diagnose in early life, and the inability to diagnose patients with atopic diseases at an early age may lead to severe complications. Numerous studies have suggested an association between the infant gut microbiome and development of allergy. In this work, we investigated the capacity of Long Short-Term Memory (...

Computational prediction of cis-regulatory elements for a set of co-expressed genes based on sequence analysis provides an overwhelming volume of potential transcription factor binding sites. It presents a challenge to prioritize a set of functional transcription factors and their binding sites on the regulatory regions of the target genes that are...

Background DNA methylation of CpG dinucleotides is an essential epigenetic modification that plays a key role in transcription. Widely used DNA enrichment-based methods offer high coverage for measuring methylated CpG dinucleotides, with the lowest cost per CpG covered genome-wide. However, these methods measure the DNA enrichment of methyl-CpG bin...

Metabolic syndrome is a multi-faceted disease. The microbiota, as a newly discovered organ, contributes to the pathogenesis and progression of metabolic syndrome. Recent studies have demonstrated that nuclear receptors play critical roles in metabolic diseases. In the current review, we discuss the general role of the microbiome in health and metab...

Bacteria sense and respond to their environments using a sophisticated array of sensors and regulatory networks to optimize their fitness and survival in a constantly changing environment. Understanding how these regulatory and sensory networks work will provide the capacity to predict bacterial behaviors and, potentially, to manipulate their inter...

Background: The heterogeneity of cells across tissue types represents a major challenge for studying biological mechanisms as well as for therapeutic targeting of distinct tissues. Computational prediction of tissue-specific gene regulatory networks may provide important insights into the mechanisms underlying the cellular heterogeneity of cells i...

Background: Microbial longitudinal studies are powerful experimental designs utilized to classify diseases, determine prognosis, and analyze microbial systems dynamics. In longitudinal studies, only identifying differential features between two phenotypes does not provide sufficient information to determine whether a change in the relative abundanc...

Motivation Accurate prediction of the host phenotype from a metgenomic sample and identification of the associated bacterial markers are important in metagenomic studies. We introduce PopPhy-CNN, a novel convolutional neural networks (CNN) learning architecture that effectively exploits phylogentic structure in microbial taxa. PopPhy-CNN provides a...

Oral tongue squamous cell carcinoma (TSCC) is a complex disease with extensive genetic and epigenetic defects, including microRNA deregulation. The aims of the present study were to test the feasibility of performing the microRNA profiling analysis on archived TSCC specimens and to assess the potential diagnostic utility of the identified microRNA...

Background DNA methylation of dinucleotide CpG is an essential epigenetic modification that plays a key role in transcription. Bisulfite conversion method is a “gold standard” for DNA methylation profiling that provides single nucleotide resolution. However, whole-genome bisulfite conversion is very expensive. Alternatively, DNA enrichment-based me...

We examine the problem of constructing fitness landscape of proteins for generating amino acid sequences that would fold into an a priori determined structural fold. Such a landscape would be useful for engineering proteins with novel or enhanced biochemistry. It should be able to characterize the global fitness landscape of many proteins simultane...

Lung transplantation offers the only treatment for multiple chronic diseases. Transplantation is dependent upon successful resistance to organ rejection. For children, a vulnerable population, the five and ten-year survival for lung transplants is only 52% and 29%, respectively. The reason for this low survival rate is primary due to chronic lung g...

Metagenomic longitudinal studies have become a widely-used study design to investigate the dynamics of the microbial ecological systems and their temporal effects. One of the important questions to be addressed in longitudinal studies is the identification of time intervals when microbial features show changes in their abundance. We propose a stati...

The microbiome has been shown to have an impact on the development of various diseases in the host. Being able to make an accurate prediction of the phenotype of a genomic sample based on its microbial taxonomic abundance profile is an important problem for personalized medicine. In this paper, we examine the potential of using a deep learning fram...

Oral tongue squamous cell carcinoma (TSCC) is a complex disease with extensive genetic and epigenetic defects, including microRNA deregulation. The aims of the present study were to test the feasibility of performing the microRNA profiling analysis on archived TSCC specimens and to assess the potential diagnostic utility of the identified microRNA...

Supplementary table S1. The levels of 12 microRNAs on 10 cases of OTSCC and paired normal tissues. Supplementary table S2. The levels of 12 microRNAs on 15 paired OTSCC and normal tissues (TCGA dataset).

[This corrects the article DOI: 10.1371/journal.pone.0163491.].

Background Metagenome shotgun sequencing presents opportunities to identify organisms that may prevent or promote disease. The analysis of sample diversity is achieved by taxonomic identification of metagenomic reads followed by generating an abundance profile. Numerous tools have been developed based on different design principles. Tools achievin...

Number of tools agreed on WEVOTE decision. (XLSX)

Running time. (XLSX)

Sensitivity and Precision. (XLSX)

Hellinger Distance. (XLSX)

Background: The identification of enhancers is a challenging task. Various types of epigenetic information including histone modification have been utilized in the construction of enhancer prediction models based on a diverse panel of machine learning schemes. However, DNA methylation profiles generated from the whole genome bisulfite sequencing (...