Quan Li

Quan Li
University of Toronto | U of T · University Health network

Ph.D

About

76
Publications
7,339
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Introduction
I am a bioinformatics researcher at University health network, University of Toronto. My research focused on human genetics ,genomics,cancers and complex diseases. I am interested in computational genomic methods/tools development.
Additional affiliations
February 2009 - November 2015
February 2009 - April 2015
McGill University
Position
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Publications

Publications (76)
Preprint
Full-text available
NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. N-alpha-acetylation is one of the most common co-translational protein modifications in humans and is essential for normal cell function. The auxiliary and regulatory subunits of the NatA complex are NAA15 and Huntington-interact...
Article
Full-text available
Genetic variants in Ankyrin Repeat Domain 11 (ANKRD11) and deletions in 16q24.3 are known to cause KBG syndrome, a rare syndrome associated with craniofacial, intellectual, and neurobehavioral anomalies. We report 25 unpublished individuals from 22 families with molecularly confirmed diagnoses. Twelve individuals have de novo variants, three have i...
Article
Several knowledgebases are manually curated to support clinical interpretations of thousands of hotspot somatic mutations in cancer. However, discrepancies or even conflicting interpretations are observed among these databases. Furthermore, many previously undocumented mutations may have clinical or functional impacts on cancer but are not systemat...
Article
Full-text available
Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. Only a fraction of NSCLC harbor actionable driver mutations and there is an urgent need for patient-derived model systems that will enable the development of new targeted therapies. NSCLC and other cancers display profound proteome remodeling compared to normal tiss...
Article
Objectives To define imaging sub-phenotypes in patients with psoriatic arthritis (PsA); determine their association with whole blood gene expression, and identify biological pathways characterizing the sub-phenotypes. Methods 55 patients with PsA ready to initiate treatment for active disease were prospectively recruited. We performed musculoskele...
Article
Full-text available
Cancer development requires a permissive microenvironment that is shaped by interactions between tumor cells, stroma, and the surrounding matrix. As collagen receptors, the leukocyte-associated immunoglobulin-like receptor (LAIR) family allows the immune system to interact with the extracellular matrix. However, little is known about their role in...
Article
Introduction: Mutations in BRAF occur in 2-4% of lung adenocarcinoma (LUAD) patients. Combination dabrafenib/trametinib or single-agent vemurafenib is approved only for patients with cancers driven by the V600E BRAF mutation. Targeted therapy is not currently available for patients harboring non-V600 BRAF mutations. Methods: An LUAD patient-deri...
Article
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Gain-of-function Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations occur in 25% of lung adenocarcinomas, and these tumors are challenging to treat. Some preclinical work, largely based on cell lines, suggested KRASmut lung cancers are especially dependent on the nuclear export protein exportin-1 (XPO1), while other work supports XPO1 bein...
Article
Background PsA patients have been observed to have a higher body mass index (BMI) compared to individuals with a similar disease (e.g., rheumatoid arthritis) or healthy controls¹. Approximately 45% of PsA patients are considered obese with BMI’s exceeding 30 kg/m², and these patients have more severe articular disease and lower response to therapy²...
Article
Background Using transcriptomic data at initiation of therapy, we recently identified differentially expressed genes (DEGs) that separated IL-17Ai response from non-response ¹ . Integration of cell-type-specific DEGs with protein-protein interactions (PPIs) and further comprehensive pathway enrichment analysis revealed Rho GTPase signaling pathway...
Article
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Patient-derived xenograft (PDX) and their xenograft-derived organoid (XDO) models that recapitulate the genotypic and phenotypic landscape of patient cancers could help to advance research and lead to improved clinical management. PDX models were established from 276 pancreato-duodenal and biliary cancer resections. Initial, passage 0 (P0) engraftm...
Article
Full-text available
Psoriatic arthritis (PsA) is a relatively common inflammatory arthritis, a spondyloarthritis (SpA), that occurs most often in patients with psoriasis, a common immune-mediated inflammatory skin disease. Both psoriasis and PsA are highly heritable. Genetic and recent genomic studies have identified variants associated with psoriasis and PsA, but var...
Preprint
Full-text available
Background: Improved understanding of the genetic architecture of psoriatic disease (PsD) and reduction in genotyping costs provide an opportunity to assess the application of genetic testing for psoriatic arthritis (PsA) diagnosis. The study aimed to assess the performance of a multi-marker genetic kit in classifying patients as PsD and PsA and to...
Preprint
Full-text available
Patient-derived xenograft (PDX) and their xenograft-derived organoid (XDO) models that recapitulate the genotypic and phenotypic landscape of patient cancers could help to advance research and lead to improved clinical management. PDX models were established from 276 pancreato-duodenal and biliary cancer resections. Initial, passage 0 (P0) engraftm...
Article
Full-text available
Background Human leukocyte antigen class 1 (HLA-1)-dependent immune activity is linked to autoimmune diseases. HLA-1-dependent CD8+ T cells are required for immune checkpoint blockade (ICB) anti-tumor activity. It is unknown if HLA-1 genotype is predictive of toxicity to ICB. Methods Patients with advanced solid tumors stratified into five cohorts...
Article
Full-text available
Biological therapies have dramatically improved the therapeutic landscape of psoriatic arthritis (PsA); however, 40–50% of patients are primary non-responders with response rates declining significantly with each successive biological therapy. Therefore, there is a pressing need to develop a coherent strategy for effective initial and subsequent se...
Preprint
Full-text available
Several knowledgebases, such as CIViC, CGI and OncoKB, have been manually curated to support clinical interpretations of somatic mutations and copy number abnormalities (CNAs) in cancer. However, these resources focus on known hotspot mutations, and discrepancies or even conflicting interpretations have been observed between these knowledgebases. T...
Article
Full-text available
Background There appears to be large regional variation for susceptibility, severity, and mortality for COVID‐19 infections. Numerous potential factors could explain the wide variability in the number of infections and death among the countries. We examined genetic differences in the human angiotensin‐converting enzyme 2 (hACE2) gene, as its recept...
Article
Background In PsA there is a pressing need to develop a coherent strategy for identifying initial and subsequent biologic responders. PsA patients present substantial heterogeneity in response to biologics, and molecular subtyping will help to identify the right patient for the right treatment. Objectives To identify transcript profiles (biomarker...
Article
Background Heterogeneity is a hallmark of psoriatic arthritis (PsA), which is reflected in diverse clinical, imaging and molecular features that may reflect disease course and response to treatment. We hypothesized that specific molecular pathways underlie the various manifestations of PsA. Objectives To create a model for accurate and biologicall...
Article
Background Improved understanding of the complex genetic architecture of psoriatic arthritis (PsA) along with the reduction in the cost of genetic testing provide an opportunity to assess the application of genetic testing for PsA diagnosis in clinical setting. Objectives The study aimed to assess the performance of the multi-SNP genetic test in p...
Article
3571 Background: Genomic events giving rise to driver negative LA in never smokers remain elusive. Here we report results of whole exome sequencing (WES) and targeted RNA sequencing in NS who had no mutation drivers found on routine clinical testing by targeted next generation sequencing (NGS). Methods: The cohort of never smokers with EGFR/ALK neg...
Article
Objective Patient-derived xenografts (PDX) are useful preclinical models to study cancer biology and mechanisms of drug response/resistance, particularly in molecularly targetable tumors. However, PDX engraftment may not be stochastic. We investigated clinical, histological and molecular features associated with PDX engraftment in a large cohort of...
Article
Background Anaplastic lymphoma kinase (ALK) targeted therapies have demonstrated remarkable efficacy in ALK-positive lung adenocarcinomas. However, patients inevitably develop resistance to such therapies. To investigate novel mechanisms of resistance to second generation ALK inhibitors, we characterized and modeled ALK inhibitor resistance of ALK-...
Preprint
Full-text available
There appears to be large regional variations for susceptibility, severity and mortality for Covid-19 infections. We set out to examine genetic differences in the human angiotensin-converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARS-CoV-2. By comparing 56,885 Non-Finnish European and 9,197 East Asians (including 1,...
Article
Full-text available
Chronic plaque psoriasis and psoriatic arthritis are multifactorial inter-related diseases with strong genetic contributions. Better elucidation of the heritability of psoriatic disease subsets is important for identifying novel genes, risk stratification and potential clinical applications. In this study, we used two mixed-effect modelling methodo...
Conference Paper
Background/Purpose: Delay in diagnosis of psoriatic arthritis (PsA) has been shown to contribute to poor radiographic and functional outcome and less successful response to treatment (Haroon et al 2015). Disease interception models are now being proposed to identify siblings at risk of psoriasis (PsC) and PsA among PsA probands, to facilitate earl...
Article
Purpose: Non-small cell lung cancer (NSCLC) is the most common cause of cancer deaths worldwide. There is an unmet need to develop novel clinically relevant models of NSCLC to accelerate identification of drug targets and our understanding of the disease. Experimental design: Thirty surgically resected NSCLC primary patient tissue and 35 previou...
Article
Concordance for type 1 diabetes is far from 100% in monozygotic twins and in the inbred NOD mice, despite genetic identity and shared environment during incidence peak years. This points to stochastic determinants such as post-zygotic mutations (PZMs) in the expanding antigen-specific autoreactive T cell lineages, by analogy to their role in the ex...
Article
We recently described a new neurodevelopmental syndrome (TAF1/MRXS33 intellectual disability syndrome) (MIM# 300966) caused by pathogenic variants involving the X‐linked gene TAF1, which participates in RNA polymerase II transcription. The initial study reported eleven families, and the syndrome was defined as presenting early in life with hypotoni...
Article
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Background: Clinical laboratories implement a variety of measures to classify somatic sequence variants and identify clinically significant variants to facilitate the implementation of precision medicine. To standardize the interpretation process, the Association for Molecular Pathology (AMP), American Society of Clinical Oncology (ASCO), and Coll...
Article
Full-text available
Whole-exome sequencing was used to identify the genetic etiology of a rapidly progressing neurological disease present in two of six siblings with early childhood onset of severe progressive spastic paraparesis and learning disabilities. A homozygous mutation (c.2005G>T, p, V669L) was found in VAC14, and the clinical phenotype is consistent with th...
Article
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Carcinoma-associated fibroblasts (CAFs) are abundant stromal cells in tumor microenvironment that are critically involved in cancer progression. Contrasting reports have shown that CAFs can have either pro- or antitumorigenic roles, indicating that CAFs are functionally heterogeneous. Therefore, to precisely target the cancer-promoting CAF subsets,...
Article
In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published updated standards and guidelines for the clinical interpretation of sequence variants with respect to human diseases on the basis of 28 criteria. However, variability between individual interpreters can be extensive beca...
Article
Full-text available
Genetic isolates provide unprecedented opportunities to identify pathogenic mutations and explore the full natural history of clinically heterogeneous phenotypes such as hearing loss. We noticed a unique audioprofile, characterized by prelingual and rapid deterioration of hearing thresholds at frequencies >0.5 kHz in several adults from unrelated f...
Article
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Background It is unclear whether and how whole-genome sequencing (WGS) data can be used to implement genomic medicine. Our objective is to retrospectively evaluate whether WGS can facilitate improving prevention and care for patients with susceptibility to cancer syndromes. Methods and Findings We analyzed genetic mutations in 60 autosomal dominan...
Data
Genetic Variants of the 300 Patients Across the 60 Cancer-Predisposition Genes. (XLS)
Data
60 Autosomal Dominant Cancer-Predisposition Genes. (XLS)
Article
Full-text available
Short-read sequencing has enabled the de novo assembly of several individual human genomes, but with inherent limitations in characterizing repeat elements. Here we sequence a Chinese individual HX1 by single-molecule real-time (SMRT) long-read sequencing, construct a physical map by NanoChannel arrays and generate a de novo assembly of 2.93 Gb (co...
Data
Supplementary Figures 1-23, Supplementary Tables 1-12, Supplementary Methods, Supplementary References
Data
A list of gaps in GRCh38 that can be closed or extended by HX1.
Article
Full-text available
The rapid progress of genomic technologies has been providing new opportunities to address the need of maturity-onset diabetes of the young (MODY) molecular diagnosis. However, whether a new mutation causes MODY can be questionable. A number of in silico methods have been developed to predict functional effects of rare human mutations. The purpose...
Article
Full-text available
Abstract The Thr allele at the Thr946Ala non-synonymous single-nucleotide polymorphism (nsSNP) in the IFIH1 gene confers risk for type 1 diabetes (T1D). IFIH1 binds viral double-stranded RNA (dsRNA), inducing a type I interferon (IFN) response. Reports of this nsSNP's role in IFIH1 expression regulation have produced conflicting results and a study...
Article
Full-text available
The search for expression quantitative trait loci has traditionally centred entirely on the process of transcription, whereas variants with effects on messenger RNA translation have not been systematically studied. Here we present a high-throughput approach for measuring translational cis-regulation in the human genome. Using ribosomal association...
Article
Full-text available
According to the ramp model of mRNA translation, the first 50 codons favor rare codons and have slower speed of translation. This study aims to detect translational selection on coding synonymous single nucleotide polymorphisms (sSNP) to support the ramp theory. We investigated fourfold degenerate site (FFDS) sSNPs with A↔G or C↔T substitutions in...
Data
Human codon usage calculated by the EMBL human coding sequences (CDS) data release 115. (DOC)
Data
Stepwise analysis of the distribution bias of FFDS sSNPs. FFDS sSNPs were analyzed in different size windows of the initial segments of coding sequences. (XLS)
Article
Background T-lymphocytes have the capacity to recognize antigens from millions of pathogens with a remarkable degree of specificity, due to the molecular diversity of the T cell receptor (TCR) repertoire. Because of this diversity, the TCR, arguably the most important molecule in both host defense and autoimmunity has been impossible to study in-de...
Article
Elevated alanine aminotransferase (ALT >40 IU/mL) is a marker of liver injury but provides little insight into etiology. We aimed to identify and stratify risk factors associated with elevated ALT in a randomly selected population with a high prevalence of elevated ALT (39%), obesity (49%) and diabetes (30%). Two machine learning methods, the suppo...
Article
Full-text available
OBJECTIVE An elevated insulin resistance index (homeostasis model assessment of insulin resistance [HOMA-IR]) is more commonly seen in the Mexican American population than in European populations. We report quantitative ancestral effects within a Mexican American population, and we correlate ancestral components with HOMA-IR.RESEARCH DESIGN AND MET...
Article
Full-text available
This study examined genetic associations of patatin-like phospholipase domain containing 3 gene (PNPLA3) polymorphisms and liver aminotransferases in an extensively documented, randomly recruited Mexican American population at high risk of liver disease. Two single nucleotide polymorphisms (SNP) in the PNPLA3 gene (i.e., rs738409 and rs2281135) wer...
Article
To analyze the correlation between insulin requirements of type 1 diabetic (T1D) patients and genotype at type 2 diabetes (T2D) risk loci, obtained in our genome-wide association study. From a database of detailed insulin dosing of 567 patients, we selected 177 for whom we also had genome-wide genotyping data. Using PLINK software, we examined the...
Article
Full-text available
The population of Han Chinese is ∼1.226 billion people. Genetic heterogeneity between northern Han Chinese (N-Han) and southern Han Chinese (S-Han) has been demonstrated by recent genome-wide studies. As an initial step toward health disparities and personalized medicine in Chinese population, this study developed a set of ancestry informative mark...
Article
Relating to our Review article published in this journal (Understanding type 1 diabetes through genetics: advances and prospects. Nature Reviews Genetics 12, 781–792)¹, we thank Kari Hemminki (Familial risks in understanding type 1 diabetes genetics. Nature Reviews Genetics 17 Jan 2012 (doi:10.1038/nrg3069-c1)
Article
Starting with early crucial discoveries of the role of the major histocompatibility complex, genetic studies have long had a role in understanding the biology of type 1 diabetes (T1D), which is one of the most heritable common diseases. Recent genome-wide association studies (GWASs) have given us a clearer picture of the allelic architecture of gen...
Article
Full-text available
Adiponectin and leptin play critical roles in the development of Metabolic Syndrome (MetS). This study was designed to assess the feasibility of using circulating levels of adiponectin and leptin for the early diagnosis of MetS. A cross-sectional study was performed using data from 367 participants randomly selected from a well-characterized cohort...
Data
The performances of machine learning methods in the identification of HOMA-IR corrected factors in the Cameron Cohort Hispanic Cohort (CCHC). (a) The SVM model; (b) The BLR model. As shown by the area under the receiver operator characteristic curve (AUROC) scores, both methods have good performance in modeling the HOMA-IR corrected factors, while...
Data
Identification of HOMA-IR corrected factors by SVM and BLR. (DOCX)