Chirag Nepal

Chirag Nepal
University of Copenhagen · Biotech Research and Innovation Centre (BRIC)

Ph.D

About

46
Publications
5,179
Reads
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1,361
Citations
Additional affiliations
June 2018 - present
University of Copenhagen
Position
  • Professor (Assistant)
June 2014 - June 2018
University of Copenhagen
Position
  • PostDoc Position
June 2013 - December 2013
University of Bergen
Position
  • Researcher
Education
October 2007 - May 2013
University of Bergen
Field of study
  • Computational Biology

Publications

Publications (46)
Preprint
Full-text available
Eukaryotic genes are regulated by multiple alternative promoters with distinct expression patterns. In cancer, alternative promoters are pervasively utilized, but our understanding of the mechanism of activation and how their regulatory architecture differs from reference promoters remains elusive. We analyzed 100 CAGE-seq libraries from HCC patien...
Article
Full-text available
Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental function...
Preprint
Full-text available
Despite being a popular model for embryonic development and diseases, zebrafish have lacked systematic functional annotation programmes seen in other animal models. To address this, we formed the international DANIO-CODE consortium and created the first central repository to store and process zebrafish functional genomic data. Our Data Coordination...
Article
Background & Aims Gallbladder cancer (GBC) is the most common type of biliary tract cancer, but the molecular mechanisms involved in gallbladder carcinogenesis remain poorly understood. In this study, we applied integrative genomics approaches to characterize GBC and explore molecular subtypes associated with patient survival. Methods We profiled...
Article
Full-text available
HOTAIR was proposed to regulate either HoxD cluster genes in trans or HoxC cluster genes in cis, a mechanism that remains unclear. We have identified a 32-nucleotide conserved noncoding element (CNE) as HOTAIR ancient sequence that likely originated at the root of vertebrate. The second round of whole-genome duplication resulted in one copy of the...
Article
Full-text available
Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Most metazoan polymerase II-transcribed genes carry canonical initiation with pyrimidine/purine (YR) dinucleotide, while translation machinery-associated genes carry polypyrimidine initiator (5’-TOP o...
Article
Cholangiocarcinoma (CCA) mortality rates are increasing due to rising incidence and limited curative treatment(s) for patients with advanced disease. NOTCH pathway reactivation has been reported in biliary malignancies to conflicting degrees, hindering prioritization of key therapeutic targets within the network and identification of candidate resp...
Preprint
Full-text available
The diversity and complexity of transcription start site (TSS) selection reflects variation of preinitiation complexes, divergent function of promoter-binding proteins and underlies not only transcriptional dynamics but may also impact on post-transcriptional fates of RNAs. The majority of metazoan genes are transcribed by RNA polymerase II from a...
Article
Full-text available
Neural stem cells (NSCs) in the adult vertebrate brain are found in a quiescent state and can preserve long-lasting progenitor potential (stemness). Whether and how these two properties are linked, and to what extent they can be independently controlled by NSC maintenance pathways, is unresolved. We previously identified Notch3 signaling as a major...
Preprint
Full-text available
HOTAIR is a long noncoding RNA transcribed between HOXC11 and HOXC12 in mammals. The proposed function(s) of HOTAIR lacks consensus as to whether it regulates HoxD cluster genes in trans or HoxC cluster genes in cis . We have identified a 32-nucleotide long conserved noncoding element (CNE) as HOTAIR ancient sequence which has a paralogous copy emb...
Article
Conclusion: Stratification of iCCA patients based on occurrence of mutations in three classifier genes (IDH, KRAS, TP53) revealed unique oncogenic programs (mutational, structural, epi-mutational) that influence pharmacologic response in drug repositioning protocols. This genome dissection approach highlights the potential of individual mutations...
Article
Full-text available
Background & aims: Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small molecule compounds that are active against CCAs. Levels of microRNA 21 (MIR21 or miRNA21) are increased in CCAs. We investigated whether miRNA21 mediates resistance of CCA cells and organoids to...
Article
Background: Aflatoxin, which is a risk factor for developing hepatocellular carcinoma, may also cause gallbladder cancer (GBC). We hypothesized that GBC patients have higher aflatoxin exposure than gallstone patients. Methods: We used samples and data from the Shanghai Biliary Tract Cancer Case-control Study conducted from 1997-2001. Of the 267 GBC...
Article
Background & aims: Aflatoxin, which causes hepatocellular carcinoma, may also cause gallbladder cancer. We investigated whether patients with gallbladder cancer have higher exposure to aflatoxin than patients with gallstones. Methods: We measured aflatoxin B1 (AFB1)-lysine adducts in plasma samples from the Shanghai Biliary Tract Cancer case-con...
Article
Full-text available
Pufferfish such as fugu and tetraodon carry the smallest genomes among all vertebrates and are ideal for studying genome evolution. However, comparative genomics using these species is hindered by the poor annotation of their genomes. We performed RNA sequencing during key stages of maternal to zygotic transition of Tetraodon nigroviridis and repor...
Article
Full-text available
MicroRNAs (miRNAs) play a major role in the post-transcriptional regulation of target genes, especially in development and differentiation. Our understanding about the transcriptional regulation of miRNA genes is limited by inadequate annotation of primary miRNA (pri-miRNA) transcripts. Here, we used CAGE-seq and RNA-seq to provide genome-wide iden...
Article
Full-text available
A core promoter is a stretch of DNA surrounding the transcription start site (TSS) that integrates regulatory inputs and recruits general transcription factors to initiate transcription. The nature and causative relationship of the DNA sequence and chromatin signals that govern the selection of most TSSs by RNA polymerase II remain unresolved. Mate...
Article
Full-text available
It was recently shown that duplications of the RevSex element, located 0.5 Mb upstream of SOX9, cause XX-disorder of sex development (DSD), and that deletions cause XY-DSD. To explore how a 148 kb RevSex duplication could have turned on gonadal SOX9 expression in the absence of SRY in an XX-male, we examined the chromatin landscape in primary skin...
Article
Full-text available
Recent meta-analyses of schizophrenia genome-wide association studies (GWASs) have identified the CUB and SUSHI multiple domains 1 (CSMD1) gene as a statistically strong risk factor. CSMD1 is a complement control-related protein suggested to inhibit the classical complement pathway, being expressed in developing neurons. However, expression of CSMD...
Article
Full-text available
Spatiotemporal control of gene expression is central to animal development. Core promoters represent a previously unanticipated regulatory level by interacting with cis-regulatory elements and transcription initiation in different physiological and developmental contexts. Here, we provide a first and comprehensive description of the core promoter r...
Article
Full-text available
Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The...
Conference Paper
Despite much progress in clinical and basic research on hepatitis C virus (HCV), interactions between HCV proteins and human proteins is not fully understood. HCV envelope proteins have many cellular targets in human proteins and affect several biological functions. From the analysis of known interactions between HCV E2 envelope proteins and human...
Article
A complete understanding of protein and RNA structures and their interactions is important for determining the binding sites in protein-RNA complexes. Computational approaches exist for identifying secondary structural elements in proteins from atomic coordinates. However, similar methods have not been developed for RNA, due in part to the very lim...
Conference Paper
Full-text available
Mining useful information from a large amount of biological data is becoming important, but most data mining research in bioinformatics is limited to molecular sequence data. We have developed a set of algorithms for analyzing hydrogen bond and van der Waals interactions between protein and RNA. Analysis of the most representative set of protein-R...
Conference Paper
Full-text available
Hepatitis C virus (HCV) remains a dangerous health problem for the reason that the mechanism of hepatocyte infection is still unknown. Hence, much attention has been put on the problem of interaction between HCV and human proteins. However, the research is still standing at the beginning point due to the lack of structure information of HCV and hum...
Chapter
Spatial reasoning is a core constituent in physical simulation, robotics, computer animation, computer-aided design, and geographic information systems. Many problems in these areas involve contact analysis and collision detection between static and/or moving objects. Due to its wide range of applications, collision detection between objects has be...

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Projects (2)