Lishuang Shen

Lishuang Shen
Children's Hospital Los Angeles | CHLA · Department of Pathology and Laboratory Medicine

Ph.D

About

123
Publications
32,283
Reads
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Introduction
I , 沈利爽,started career in web-lab genetics and rice genomics in 中科院遗传所. Prof. Lihuang Zhu was my Ph.D. mentor. I transited to bioinformatics in 2003 after 2 years of course work. I worked on genomic and epigenomic projects in human and other species, including 5 years in diabetes, cancer, and Mendelian diseases. I'm building resources for mitochondrial diseases (mseqdr.org) and pipelines in personalized medicine. I focus on NGS data analysis and warehousing, Chip-seq, RNA-seq, methylation, and variation (SNP/Indel/SV) discovery.
Additional affiliations
August 2015 - present
Children's Hospital Los Angeles
Position
  • Bioinformatician
Description
  • • R & D of NGS-based genetic disease and tumor diagnosis through CES/Panel/Liquid biopsy assays. • Build new bioinformatics hardware and software platform from scratch, combing local HPC with Amazon AWS cloud platforms. • Lead Bioinformatician for MSeqDR Mitochondrial Disease Sequence Data Resource Consortium. • Editor for <MEDICINE>, reviewer for multiple medical, genomics & bioinformatics journals. • SARS-CoV-2 Coronavirus and TB infectious microbe genomics and epidemiology.
January 2014 - July 2015
MEEI, Harvard Medical School
Position
  • Bioinformaticist
August 1997 - November 1999
International Rice Research Institute
Position
  • Project Scientist
Description
  • The best of my life, the people, the institute, and the born of my son.

Publications

Publications (123)
Research
Full-text available
I am honored to become a full member of Sigma Xi, The Scientific Research Honor Society. Sigma Xi is the international honor society of science and engineering and is one of the oldest and largest scientific organizations in the world. The organization was founded in 1886 to honor excellence in scientific investigation and encourage a sense of co...
Article
The international Mitochondrial Disease Sequence Data Resource Consortium (MSeqDR) Quick‐Mitome (QM) is a web‐based platform enabling automated variant interpretation of whole‐exome sequencing (WES) datasets for the genetic diagnosis of primary mitochondrial diseases (PMD). Designed specifically to address the unique dual genome nature of PMD etiol...
Article
Objective: Primary mitochondrial diseases (PMDs) are heterogeneous disorders caused by inherited mitochondrial dysfunction. Classically defined neuropathologically as subacute necrotizing encephalomyelopathy, Leigh syndrome spectrum (LSS) is the most frequent manifestation of PMD in children, but may also present in adults. A major challenge for a...
Article
Full-text available
We characterized the world’s second case with ascertained extreme resilience to autosomal dominant Alzheimer’s disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact...
Preprint
Full-text available
The significantly greater infectivity of the SARS-CoV-2 Delta variants of concern (VOC) is hypothesized to be driven by key mutations that result in increased transmissibility, viral load and/or evasion of host immune response. We surveyed the mutational profiles of Delta VOC genomes between September 2020 and mid-August 2021 and identified a previ...
Conference Paper
p>Purpose: Germline alterations in the RB1 tumor suppressor gene predispose patients to developing retinoblastoma (RB) in both eyes. However, tumors in bilateral RB may not respond identically to treatment. The additional genomic events that occur independently in each eye during tumorigenesis are not well characterized. The aqueous humor (AH) prov...
Article
Full-text available
Germline alterations in the RB1 tumor suppressor gene predispose patients to develop retinoblastoma (RB) in both eyes. While similar treatment is given for each eye, there is often a variable therapeutic response between the eyes. Herein, we use the aqueous humor (AH) liquid biopsy to evaluate the cell-free tumor DNA (ctDNA) from each eye in a pati...
Article
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The SARS-CoV-2 B.1.1.7 lineage is highly infectious and as of April 2021 accounted for 92% of COVID-19 cases in Europe and 59% of COVID-19 cases in the U.S. It is defined by the N501Y mutation in the receptor binding domain (RBD) of the Spike (S) protein, and a few other mutations. These include two mutations in the N terminal domain (NTD) of the S...
Preprint
Full-text available
The evolution of SARS-CoV2 virus has led to the emergence of variants of concern (VOC). Children, particularly <12 years old not yet eligible for vaccines, continue to be important reservoirs of SARS-CoV-2 yet VOC prevalence data in this population is lacking. We report data from a genomic surveillance program that includes 9 U.S. children's hospit...
Preprint
Full-text available
The SARS-CoV-2 B.1.1.7 lineage is highly infectious and as of April 2021 accounted for 92% of COVID-19 cases in Europe and 59% of COVID-19 cases in the U.S. It is defined by the N501Y mutation in the receptor binding domain (RBD) of the Spike (S) protein, and a few other mutations. These include two mutations in the N terminal domain (NTD) of the S...
Article
Full-text available
Mutations in the SARS-CoV-2 Membrane (M) gene are relatively uncommon. The M gene encodes the most abundant viral structural protein, and is implicated in multiple viral functions, including initial attachment to the host cell via heparin sulfate proteoglycan, viral protein assembly in conjunction with the N and E genes, and enhanced glucose transp...
Article
Full-text available
Background: There is increasing concern that persistent infection of SARS-CoV-2 within immunocompromised hosts could serve as a reservoir for mutation accumulation and subsequent emergence of novel strains with the potential to evade immune responses. Methods: We describe three patients with acute lymphoblastic leukemia who were persistently pos...
Article
Full-text available
Because direct tumor biopsy is prohibited for retinoblastoma (RB), eye-specific molecular biomarkers are not used in clinical practice for RB. Recently, we demonstrated that the aqueous humor (AH) is a rich liquid biopsy source of cell-free tumor DNA. Herein, we detail clinically-relevant molecular biomarkers from the first year of prospective vali...
Preprint
Full-text available
Mutations in the SARS-CoV-2 Membrane (M) gene are relatively uncommon. The M gene encodes the most abundant viral structural protein, and is implicated in multiple viral functions, including initial attachment to the host cell via heparin sulfate proteoglycan, viral protein assembly in conjunction with the N and E genes, and enhanced glucose transp...
Preprint
Full-text available
Background There is increasing concern that persistent infection of SARS-CoV-2 within immunocompromised hosts could serve as a reservoir for mutation accumulation and subsequent emergence of novel strains with the potential to evade immune responses. Methods We describe three patients with acute lymphoblastic leukemia who were persistently positive...
Article
Full-text available
Objectives Pseudomonas aeruginosa is a leading cause of opportunistic infections worldwide, particularly in healthcare settings, and frequently demonstrates resistance to commonly prescribed antimicrobials. Carbapenem resistance is prevalent worldwide; however, there are currently limited data available from Haiti. The aim of this study was to char...
Preprint
Full-text available
Background In the US, community circulation of the SARS-CoV-2 virus likely began in February 2020 after mostly travel-related cases. Children's Hospital of Philadelphia began testing on 3/9/2020 for pediatric and adult patients, and for all admitted patients on 4/1/2020, allowing an early glimpse into the local molecular epidemiology of the virus....
Article
Full-text available
Background Full spectrum of disease phenotype and viral genotype of COVID-19 have yet to be thoroughly explored in children. Here, we analyze the relationships between viral genetic variants and clinical characteristics in children. Methods Whole genome sequencing was performed on respiratory specimens collected on all SARS-CoV-2 positive children...
Conference Paper
Many detection methods have been used or reported for the diagnosis and/or surveillance of COVID-19. Among them, reverse transcription polymerase chain reaction (RT-PCR) is the most commonly used because of its high sensitivity, typically claiming detection of about 5 copies of viruses. However, it has been reported that only 47-59% of the positive...
Article
Mitochondrial DNA (mtDNA) variant pathogenicity interpretation has special considerations given unique features of the mtDNA genome, including maternal inheritance, variant heteroplasmy, threshold effect, absence of splicing, and contextual effects of haplogroups. Currently there are insufficient standardized criteria for mtDNA variant assessment,...
Article
Full-text available
Genomic analysis of SARS-CoV-2 sequences is crucial in determining the effectiveness of prudent safer at home measures in the United States (US). By haplotype analysis of 6,356 US isolates, we identified a pattern of strongly localized outbreaks at the city-, state-, and country-levels, and temporal transmissions. This points to the effectiveness o...
Article
Results Four of 7 AH samples contained clinically significant SCNAs. Of the 3 other samples, 1 showed focal MYCN amplification and 1 showed focal RB1 deletion. All 4 enucleated tumors contained SCNAs. Mutational analysis of tumor DNA identified all first hits (2 germline RB1 SNVs, 2 germline CNAs) and second hits (4 RB1 SNVs). RB1 variants in AH we...
Conference Paper
Purpose: Retinoblastoma (RB) tumorigenesis is associated with mutations in the RB1 tumour suppressor gene and somatic copy number alterations (SCNAs). Both alleles of the RB1 gene must be mutated for tumour development. The initial RB1 mutation may be germline or somatic. However, the somatic RB1 mutation was only detectable in enucleated RB eyes,...
Preprint
Full-text available
Understanding the genetic etiology of COVID-19 requires a comprehensive understanding of the variant and haplotype landscape of all reported genomes of SARS-COV-2, the causative virus of the disease. Country-, state/region- and possibly even city-private variant profiles may contribute to varied disease exemplifications and fatality rates observed...
Article
Clinical bioinformatics system is well-established for diagnosing genetic disease based on next-generation sequencing, but requires special considerations when being adapted for the next-generation sequencing-based genetic diagnosis of mitochondrial diseases. Challenges are caused by the involvement of mitochondrial DNA genome in disease etiology....
Preprint
Full-text available
Clinical presentation of COVID-19 in children remains under investigation. In this manuscript, we present a summary of clinical findings from the first 23 cases of COVID-19 in children at Children's Hospital Los Angeles. Considering the paucity of genomics data for circulating SARS-CoV-2 isolates in Southern California, we also present an overview...
Preprint
Full-text available
Genomic analysis of SARS-CoV-2 sequences is crucial in determining the effectiveness of prudent safer at home measures in the United States (US). By haplotype analysis of 6,356 US isolates, we identified a pattern of strongly localized outbreaks at the city-, state-, and country-levels, and temporal transmissions. This points to the effectiveness o...
Preprint
Full-text available
Effective response to the Coronavirus Disease 2019 (COVID-19) pandemic requires genomic resources and bioinformatics tools for genomic epidemiology and surveillance studies that involve characterizing full-length viral genomes, identifying origins of infections, determining the relatedness of viral infections, performing phylogenetic analyses, and...
Chapter
This book was designed to provide a readily usable clinical compendium of all forms of mitochondrial disease from the perspective of individual causal disease genes. As such, this book will serve as a generally approachable companion to gain access to the more comprehensive set of highly detailed data and informatics resources available in the Mito...
Book
About the book Description The field of Mitochondrial Medicine has been dominated by symptom constellation-based diagnostic categorization since the first clinical syndrome was described three decades ago. Now, as rapidly expanding knowledge has revealed that mitochondrial diseases may result from several hundred distinct gene disorders with exten...
Article
Full-text available
We identified a PSEN1 (presenilin 1) mutation carrier from the world’s largest autosomal dominant Alzheimer’s disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amylo...
Poster
MSeqDR (https://mseqdr.org) is a centralized genomic bioinformatics Web resource that supports genetic analyses and variant interpretation for people working in mitochondrial biology and disease. MSeqDR is a central data resource hub for the mitochondrial disease community, including MitoMap, HmtDB, LeighMap, ClinVar, ClinGen, PhenoTips, and GENOMI...
Article
Full-text available
Mitochondrial DNA (mtDNA) genome integrity is essential for proper mitochondrial respiratory chain function to generate cellular energy. Nuclear genes encode several proteins that function at the mtDNA replication fork, including mitochondrial single-stranded DNA-binding protein (SSBP1), which is a tetrameric protein that binds and protects single-...
Article
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Advancing the clinical utility of whole-exome sequencing (WES) for patients with suspected genetic disorders is largely driven by bioinformatics approaches that streamline data processing and analysis. Herein, we describe our experience with implementing a semiautomated and phenotype-driven WES diagnostic workflow, incorporating both the DRAGEN pip...
Article
Accurate mitochondrial DNA (mtDNA) variant annotation is essential for the clinical diagnosis of diverse human diseases. Substantial challenges to this process include the inconsistency in mtDNA nomenclatures, the existence of multiple reference genomes, and a lack of reference population frequency data. Clinicians need a simple bioinformatics tool...
Article
Rare or novel gene variants in patients with proliferative diabetic retinopathy may contribute to disease development. We performed whole exome sequencing (WES) on patients at the phenotypic extremes of diabetic retinal complications: 57 patients diagnosed with proliferativediabetic retinopathy (PDR) as cases and 13 patients with no diabetic retino...
Article
Full-text available
Proliferative diabetic retinopathy (PDR) is a common cause of blindness in the developed world's working adult population, and affects those with type 1 and type 2 diabetes mellitus. We identified Runt-related transcription factor 1 (RUNX1) as a gene upregulated in CD31+ vascular endothelial cells obtained from human PDR fibrovascular membranes (FV...
Article
Full-text available
We report a family in which two brothers had an undiagnosed genetic disorder comprised of dysmorphic features, microcephaly, severe intellectual disability (non-verbal), mild anemia, and cryptorchidism. Both developed osteosarcoma. Trio exome sequencing (using blood samples from the younger brother and both parents) was performed and a nonsense NM_...
Article
Full-text available
The HmtDB resource hosts a database of human mitochondrial genome sequences from individuals with healthy and disease phenotypes. The database is intended to support both population geneticists as well as clinicians undertaking the task to assess the pathogenicity of specific mtDNA mutations. The wide application of next-generation sequencing (NGS)...
Article
Human cancer genome studies have identified the SWI/SNF chromatin remodeling complex member ARID1A as one of the most frequently altered genes in several tumor types. Its role as an ovarian tumor suppressor has been supported in compound knockout mice. Here, we provide genetic and functional evidence that Arid1a is a bona fide mammary tumor suppres...
Article
Full-text available
Purpose: Identifying genetic risk factors for developing sarcoidosis-associated uveitis could provide insights into its pathogenesis which is poorly understood. We determine if variants in NOD2 confer an increased risk of developing uveitis in adults with sarcoidosis. Methods: In this genetic case-control study, 51 total subjects were enrolled: 39...
Conference Paper
The X-linked alpha-thalassemia/intellectual disability syndrome (ATR-X) is a disorder predominantly affecting males, and is characterized by severe intellectual disability, mild Hemoglobin H disease, dysmorphic facies, genital anomalies, and skeletal abnormalities. ATR-X syndrome is caused by germline pathogenic variants in the ATRX gene. The first...
Article
MSeqDR is the Mitochondrial Disease Sequence Data Resource, a centralized and comprehensive genome and phenome bioinformatics resource built by the mitochondrial disease community to facilitate clinical diagnosis and research investigations of individual patient phenotypes, genomes, genes, and variants. A central Web portal (https://mseqdr.org) int...
Article
Full-text available
The World Health Organization recommends diagnosing Multidrug-Resistant Tuberculosis (MDR-TB) in high burden countries by detection of mutations in Rifampin (RIF) Resistance Determining Region of Mycobacterium tuberculosis rpoB gene with rapid molecular tests GeneXpert MTB/RIF and Hain MTBDRplus. Such mutations are found in >95% of Mycobacterium tu...
Article
Common variable immunodeficiency (CVID) is a late-onset humoral deficiency characterized by B lymphocyte dysfunction or loss, decreased immunoglobulin production, and recurrent bacterial infections. CVID is the most frequent human primary immunodeficiency but still presents challenges in the understanding of its etiology and treatment. CVID in equi...
Article
Full-text available
All current mitochondrial haplogroup classification tools require variants to be detected from an alignment with the reference sequence and to be properly named according to the canonical nomenclature standards for describing mitochondrial variants, before they can be compared to the haplogroup determining polymorphisms. With the emergence of high-...
Article
Full-text available
Identifying genomic alterations driving breast cancer is complicated by tumor diversity and genetic heterogeneity. Relevant mouse models are powerful for untangling this problem because such heterogeneity can be controlled. Inbred Chaos3 mice exhibit high levels of genomic instability leading to mammary tumors that have tumor gene expression profil...
Article
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The transcriptional regulation of mammalian meiosis is poorly characterized, owing to few genetic and ex vivo models. From a genetic screen, we identify the transcription factor MYBL1 as a male-specific master regulator of several crucial meiotic processes. Spermatocytes bearing a novel separation-of-function allele (Mybl1(repro9)) had subtle defec...
Article
Full-text available
Forward genetic screens in mice provide an unbiased means to identify genes and other functional genetic elements in the genome. Previously, a large scale ENU mutagenesis screen was conducted to query the functional content of a ~50 Mb region of the mouse genome on proximal Chr 5. The majority of phenotypic mutants recovered were embryonic lethals....
Article
Full-text available
Genome-wide association studies have identified common variants that only partially explain the genetic risk for type 2 diabetes (T2D). Using genome-wide association data from 1,376 French individuals, we identified 16,360 SNPs nominally associated with T2D and studied these SNPs in an independent sample of 4,977 French individuals. We then selecte...
Article
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Nat. Genet. 41, 1110–1115; published online 6 September; corrected online 13 September 2009 In the version of this article initially published online, there were errors in the e-mail addresses of two of the corresponding authors. The correct e-mail address for Robert Sladek is e-mail: robert.sladek@mcgill.ca; the correct e-mail address for Philipp...
Article
Full-text available
Type 2 diabetes mellitus results from the interaction of environmental factors with a combination of genetic variants, most of which were hitherto unknown. A systematic search for these variants was recently made possible by the development of high-density arrays that permit the genotyping of hundreds of thousands of polymorphisms. We tested 392,93...
Article
Full-text available
Type 2 diabetes mellitus results from the interaction of environmental factors with a combination of genetic variants, most of which were hitherto unknown. A systematic search for these variants was recently made possible by the development of high-density arrays that permit the genotyping of hundreds of thousands of polymorphisms. We tested 392,93...
Article
BarleyBase (http://barleybase.org/) and its successor, PLEXdb (http://plexdb.org/), are public resources for large-scale gene expression analysis for plants and plant pathogens. BarleyBase/PLEXdb provides a unified web interface to support the functional interpretation of highly parallel microarray experiments integrated with traditional structural...
Article
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BarleyExpress is a web-based microarray experiment data submission tool for BarleyBase, a public data resource of Affymetrix GeneChip® data for plants. BarleyExpress uses the Plant Ontology vocabularies and enhances the MIAME guidelines to standardize the annotation of microarray gene expression experiments. In addition, BarleyExpress provides expl...