Annie W. Shieh
A5036796031- Genetic Associations and Epidemiology
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Genomic variations and chromosomal abnormalities
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- HIV Research and Treatment
- Protist diversity and phylogeny
- Tryptophan and brain disorders
- Genetic Mapping and Diversity in Plants and Animals
- Muscle Physiology and Disorders
- Chromosomal and Genetic Variations
- Bacteriophages and microbial interactions
- Genomics and Rare Diseases
- Optical Imaging and Spectroscopy Techniques
- Virus-based gene therapy research
- Advanced Neuroimaging Techniques and Applications
- Cell Image Analysis Techniques
- Cancer Genomics and Diagnostics
University of Chicago
2022-2024
Brown Foundation
2022-2023
Center for Human Genetics
2022-2023
The University of Texas Health Science Center at Houston
2022-2023
University of Illinois Chicago
2015-2022
SUNY Upstate Medical University
2018-2021
San Francisco State University
2019-2020
Washington University in St. Louis
2012-2013
Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments transcriptomic organization diseased brains are limited. In this work, we integrated genotypes RNA sequencing brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, bipolar disorder, as well controls. More than 25% the transcriptome exhibits differential splicing or expression,...
INTRODUCTION The brain is responsible for cognition, behavior, and much of what makes us uniquely human. development the a highly complex process, this process reliant on precise regulation molecular cellular events grounded in spatiotemporal transcriptome. Disruption can lead to neuropsychiatric disorders. RATIONALE regulatory, epigenomic, transcriptomic features human have not been comprehensively compiled across time, regions, or cell types. Understanding etiology disorders requires...
Schizophrenia genome-wide association studies have identified >150 regions of the genome associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore mechanism non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals schizophrenia and 137 controls, 118,152 peaks. These accessible chromatin are highly enriched for SNP heritability. Accessible overlap...
POU3F2 regulates expression of key genes in postmortem brain tissue from patients with schizophrenia or bipolar disorder.
Cellular heterogeneity in the human brain obscures identification of robust cellular regulatory networks, which is necessary to understand function non-coding elements and impact genetic variation. Here we integrate genome-wide chromosome conformation data from purified neurons glia with transcriptomic enhancer profiles, characterize gene landscape two major cell classes brain. We then leverage cell-type-specific landscapes gain insight into etiology several disorders. find that Alzheimer's...
Myogenic differentiation of human pluripotent stem cells (hPSCs) has been done by gene overexpression or directed differentiation. However, viral integration, long-term culture, and the presence unwanted are main obstacles. By using CRISPR/Cas9n, a double-reporter embryonic cell (hESC) line was generated for PAX7/MYF5, allowing prospective readout. This strategy allowed pathway screen to define efficient myogenic induction in hPSCs. Next, surface marker identification CD10 CD24 purification...
Abstract Psychiatric disorders are highly heritable yet polygenic, potentially involving hundreds of risk genes. Genome-wide association studies have identified genomic susceptibility loci with to psychiatric disorders; however, the contribution these underlying psychopathology and etiology remains elusive. Here we generated deep human brain proteomics data by quantifying 11,608 proteins across 268 subjects using 11-plex tandem mass tag coupled two-dimensional liquid chromatography-tandem...
Genetic variants may lead to disease, denoted here by a dimmed letter representing nucleotide. The PsychENCODE Consortium presents research link the effects of genetic variation gene expression in brain.
During macronuclear differentiation of the ciliate Tetrahymena thermophila, genome-wide DNA rearrangements eliminate nearly 50 Mbp germline derived DNA, creating a streamlined somatic genome. The transposon-like and other repetitive sequences to be eliminated are identified using piRNA pathway packaged as heterochromatin prior their removal. In this study, we show that LIA5, which encodes zinc-finger protein likely transposon origin, is required for both chromosome fragmentation elimination...
Abstract Positive effects of alcohol drinking such as anxiolysis and euphoria appear to be a crucial factor in the initiation maintenance use disorder (AUD). However, mechanisms that lead from chromatin reorganization transcriptomic changes after acute ethanol exposure remain unknown. Here, we used Assay for Transposase-Accessible Chromatin followed by high throughput sequencing (ATAC-seq) RNA-seq investigate epigenomic underlie anxiolytic using an animal model. Analysis ATAC-seq data...
Mutations can occur throughout the virus genome and may be beneficial, neutral or deleterious. We are interested in mutations that yield a C next to G, producing CpG sites. sites rare eukaryotic viral genomes. For eukaryotes, it is thought because they prone mutation when methylated. In viruses, we know less about why rare. A previous study HIV suggested CpG-creating transition more costly than similar non-CpG-creating mutations. To determine if this case other analyzed allele frequencies of...
The impact of genetic variants on gene expression has been intensely studied at the transcription level, yielding in valuable insights into association between genes and risk complex disorders, such as schizophrenia (SCZ). However, downstream these molecular mechanisms connecting variation to disease are not well understood.We quantitated ribosome occupancy prefrontal cortex samples BrainGVEX cohort. Together with transcriptomics proteomics data from same cohort, we performed...
Studies of complex disorders benefit from integrative analyses multiple omics data. Yet, sample mix-ups frequently occur in multi-omics studies, weakening statistical power and risking false findings. Accurately aligning information, genotype, corresponding data is critical for analyses. We developed DRAMS (https://github.com/Yi-Jiang/DRAMS) to Detect Re-Align Mixed-up Samples address the mix-up problem. It uses a logistic regression model followed by modified topological sorting algorithm...
Autosomal recessive limb-girdle muscular dystrophy 21 (LGMDR21) is caused by pathogenic variants in protein O-glucosyltransferase 1 (POGLUT1), which responsible for O-glucosylation of specific epidermal growth factor (EGF) repeats found ∼50 mammalian proteins, including Notch receptors. Previous data from patient biopsies indicated that impaired signaling, reduction muscle stem cells, and accelerated differentiation are probably involved disease etiopathology. Using induced pluripotent cells...
<title>Abstract</title> Psychiatric disorders are highly heritable yet polygenetic, potentially involving hundreds of risk genes. Genome-wide association studies (GWAS) have identified genomic susceptibility loci for psychiatric disorders, but how these contribute to the underlying psychopathology and etiology remains elusive. Here we generated a deep human brain proteome by quantifying 11,672 proteins across 288 subjects using 11-plex tandem mass tag (TMT) coupled with two-dimensional...
Acute cellular stress is known to induce a global reduction in mRNA translation through suppression of cap dependent translation. Selective response acute has been shown play important roles regulating the response. However, accurately profiling translational changes transcriptome-wide challenging. Commonly used data normalization methods operate on assumption that any systematic shifts are experimental artifacts. Consequently, if applied stress-induced changes, these expected produce biased...
Abstract Mutations can occur throughout the virus genome and may be beneficial or deleterious. We are interested in mutations that yield a C next to G, producing CpG sites. sites rare eukaryotic viral genomes. For eukaryotes, it is thought because they prone mutation when methylated. In viruses, we know less about why rare. A previous study HIV suggested CpG-creating transition more costly similar non-CpG-creating mutations. To determine if this case other analyzed allele frequencies of...
Abstract Studies of complex disorders benefit from integrative analyses multiple omics data. Yet, sample mix-ups frequently occur in multi-omics studies, weakening statistical power and risking false findings. Accurately aligning information, genotype, corresponding data is critical for analyses. We developed DRAMS ( https://github.com/Yi-Jiang/DRAMS ) to Detect Re-Align Mixed-up Samples address the mix-up problem. It uses a logistic regression model followed by modified topological sorting...
Abstract Acute cellular stress is known to induce a global reduction in protein translation through suppression of cap dependent translation. However, selective response acute has been shown play important roles regulating the response. An accurate transcriptome-wide profile stress-induced translational changes challenging obtain. Commonly used data normalization methods, such as quantile normalization, operate based on assumption that any systematic shifts are artifacts introduced from...