Abhishek Shah - Academia.edu (original) (raw)

Papers by Abhishek Shah

Research paper thumbnail of RNA-Seq of Human Neurons Derived from iPS Cells Reveals Candidate Long Non-Coding RNAs Involved in Neurogenesis and Neuropsychiatric Disorders

PLOS One, 2011

Genome-wide expression analysis using next generation sequencing (RNA-Seq) provides an opportunit... more Genome-wide expression analysis using next generation sequencing (RNA-Seq) provides an opportunity for in-depth molecular profiling of fundamental biological processes, such as cellular differentiation and malignant transformation. Differentiating human neurons derived from induced pluripotent stem cells (iPSCs) provide an ideal system for RNA-Seq since defective neurogenesis caused by abnormalities in transcription factors, DNA methylation, and chromatin modifiers lie at the heart of some neuropsychiatric disorders. As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs), pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ), bipolar disorder (BD) and autism spectrum disorders (ASD) that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients.

Research paper thumbnail of Catenin Promoter ChIP-Chip Reveals Potential Schizophrenia and Bipolar Disorder Gene Network

Journal of Neurogenetics, 2010

Therapeutic concentrations of lithium salts inhibit glycogen synthase kinase 3 beta (GSK3β) and p... more Therapeutic concentrations of lithium salts inhibit glycogen synthase kinase 3 beta (GSK3β) and phosphoinositide (PI) signaling suggesting that abnormal activation of these pathways could be a factor in the pathophysiology of bipolar disorder (BD). Involvement of these pathways is also supported by recent genome-wide association studies (GWASs). One way investigators have investigated the molecular basis of BD and the therapeutic action of lithium is by microarray expression studies, since both GSK3β- and PI-mediated signal transduction pathways are coupled to transcriptional activation and inhibition. However, expression profiling has some limitations and investigators cannot use the approach to analyze fetal brain tissue, arguably the most relevant biological structure related to the development of genetically based psychiatric disorders. To address these shortcomings, the authors have taken a novel approach using chromatin immunoprecipitation-enriched material annealed to microarrays (ChIP-chip) targeting genes in fetal brain tissue bound by β-catenin, a transcription factor that is directly regulated by GSK3β. The promoters for 640 genes were found to be bound by β-catenin, many of which are known schizophrenia (SZ), autism spectrum disorder (ASD), and BD candidates, including CACNA1B, NRNG, SNAP29, FGFR1, PCDH9, and nine others identified in recently published GWASs and genome-wide searches for copy number variants (CNVs). The findings suggest that seemingly disparate candidate genes for SZ and BD can be incorporated into a common molecular network revolving around GSK3β/β-catenin signaling. In addition, the finding that a putative lithium-responsive pathway may influence a subgroup of SZ and ASD candidate genes could have therapeutic implications.

Research paper thumbnail of A Study of Digital Image Filtering Techniques in Spatial Image Processing

Digital Image Processing refers to processing digital images by means of digital computer [1]. Fo... more Digital Image Processing refers to processing digital images by means of digital computer [1]. For Digital Image Processing Algorithm input image is obtained by image input devices such as digital cameras. Different types of noise got added while image is obtaining from image input devices. This noise degrades the quality of image. Noise can be removed by various image filtering techniques. Image filtering is the process of remove noise from image. Digital image filtering can be either spatial domain or frequency domain. This Paper describes various digital image filtering techniques in spatial domain.

Research paper thumbnail of RNA-Seq of Human Neurons Derived from iPS Cells Reveals Candidate Long Non-Coding RNAs Involved in Neurogenesis and Neuropsychiatric Disorders

PLOS One, 2011

Genome-wide expression analysis using next generation sequencing (RNA-Seq) provides an opportunit... more Genome-wide expression analysis using next generation sequencing (RNA-Seq) provides an opportunity for in-depth molecular profiling of fundamental biological processes, such as cellular differentiation and malignant transformation. Differentiating human neurons derived from induced pluripotent stem cells (iPSCs) provide an ideal system for RNA-Seq since defective neurogenesis caused by abnormalities in transcription factors, DNA methylation, and chromatin modifiers lie at the heart of some neuropsychiatric disorders. As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs), pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ), bipolar disorder (BD) and autism spectrum disorders (ASD) that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients.

Research paper thumbnail of Catenin Promoter ChIP-Chip Reveals Potential Schizophrenia and Bipolar Disorder Gene Network

Journal of Neurogenetics, 2010

Therapeutic concentrations of lithium salts inhibit glycogen synthase kinase 3 beta (GSK3β) and p... more Therapeutic concentrations of lithium salts inhibit glycogen synthase kinase 3 beta (GSK3β) and phosphoinositide (PI) signaling suggesting that abnormal activation of these pathways could be a factor in the pathophysiology of bipolar disorder (BD). Involvement of these pathways is also supported by recent genome-wide association studies (GWASs). One way investigators have investigated the molecular basis of BD and the therapeutic action of lithium is by microarray expression studies, since both GSK3β- and PI-mediated signal transduction pathways are coupled to transcriptional activation and inhibition. However, expression profiling has some limitations and investigators cannot use the approach to analyze fetal brain tissue, arguably the most relevant biological structure related to the development of genetically based psychiatric disorders. To address these shortcomings, the authors have taken a novel approach using chromatin immunoprecipitation-enriched material annealed to microarrays (ChIP-chip) targeting genes in fetal brain tissue bound by β-catenin, a transcription factor that is directly regulated by GSK3β. The promoters for 640 genes were found to be bound by β-catenin, many of which are known schizophrenia (SZ), autism spectrum disorder (ASD), and BD candidates, including CACNA1B, NRNG, SNAP29, FGFR1, PCDH9, and nine others identified in recently published GWASs and genome-wide searches for copy number variants (CNVs). The findings suggest that seemingly disparate candidate genes for SZ and BD can be incorporated into a common molecular network revolving around GSK3β/β-catenin signaling. In addition, the finding that a putative lithium-responsive pathway may influence a subgroup of SZ and ASD candidate genes could have therapeutic implications.

Research paper thumbnail of A Study of Digital Image Filtering Techniques in Spatial Image Processing

Digital Image Processing refers to processing digital images by means of digital computer [1]. Fo... more Digital Image Processing refers to processing digital images by means of digital computer [1]. For Digital Image Processing Algorithm input image is obtained by image input devices such as digital cameras. Different types of noise got added while image is obtaining from image input devices. This noise degrades the quality of image. Noise can be removed by various image filtering techniques. Image filtering is the process of remove noise from image. Digital image filtering can be either spatial domain or frequency domain. This Paper describes various digital image filtering techniques in spatial domain.