Abstract:
BACKGROUND:Pancreatic cancer is a deadly disease with a five-year survival of less than 5%. A better understanding of the underlying biology may suggest novel therapeutic targets. Recent surveys of the pancreatic cancer genome have uncovered numerous new alterations; yet systematic functional characterization of candidate cancer genes has lagged behind. To address this challenge, here we have devised a highly-parallel RNA interference-based functional screen to evaluate many genomically-nominated candidate pancreatic cancer genes simultaneously. RESULTS:For 185 candidate pancreatic cancer genes, selected from recurrently altered genomic loci, we performed a pooled shRNA library screen of cell growth/viability across 10 different cell lines. Knockdown-associated effects on cell growth were assessed by enrichment or depletion of shRNA hairpins, by hybridization to barcode microarrays. A novel analytical approach (COrrelated Phenotypes for On-Target Effects; COPOTE) was used to discern probable on-target knockdown, based on identifying different shRNAs targeting the same gene and displaying concordant phenotypes across cell lines. Knockdown data were integrated with genomic architecture and gene-expression profiles, and selected findings validated using individual shRNAs and/or independent siRNAs. The pooled shRNA library design delivered reproducible data. In all, COPOTE analysis identified 52 probable on-target gene-knockdowns. Knockdown of known oncogenes (KRAS, MYC, SMURF1 and CCNE1) and a tumor suppressor (CDKN2A) showed the expected contrasting effects on cell growth. In addition, the screen corroborated purported roles of PLEKHG2 and MED29 as 19q13 amplicon drivers. Most notably, the analysis also revealed novel possible oncogenic functions of nucleoporin NUP153 (ostensibly by modulating TGFβ signaling) and Kruppel-like transcription factor KLF5 in pancreatic cancer. CONCLUSIONS:By integrating physical and functional genomic data, we were able to simultaneously evaluate many candidate pancreatic cancer genes. Our findings uncover new facets of pancreatic cancer biology, with possible therapeutic implications. More broadly, our study provides a general strategy for the efficient characterization of candidate genes emerging from cancer genome studies.
journal_name
BMC Genomicsjournal_title
BMC genomicsauthors
Shain AH,Salari K,Giacomini CP,Pollack JRdoi
10.1186/1471-2164-14-624subject
Has Abstractpub_date
2013-09-16 00:00:00pages
624issn
1471-2164pii
1471-2164-14-624journal_volume
14pub_type
杂志文章相关文献
BMC GENOMICS文献大全abstract:BACKGROUND:Whole-genome sequencing is an important method to understand the genetic information, gene function, biological characteristics and survival mechanisms of organisms. Sequencing large genomes is very simple at present. However, we encountered a hard-to-sequence genome of Pseudomonas aeruginosa phage PaP1. Sho...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-15-803
更新日期:2014-09-19 00:00:00
abstract:BACKGROUND:Alternative splicing (AS) is a central mechanism in the generation of genomic complexity and is a major contributor to transcriptome and proteome diversity. Alterations of the splicing process can lead to deregulation of crucial cellular processes and have been associated with a large spectrum of human disea...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-11-S5-S4
更新日期:2010-12-22 00:00:00
abstract:BACKGROUND:RNA-seq and microarray are the two popular methods employed for genome-wide transcriptome profiling. Current comparison studies have shown that transcriptome quantified by these two methods correlated well. However, none of them have addressed if they complement each other, considering the strengths and the ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-13-629
更新日期:2012-11-15 00:00:00
abstract:BACKGROUND:Aedes aegypti is the principle vector of many arboviruses, including dengue virus and Zika virus, which are transmitted when an infected female mosquito takes a blood meal in order to initiate vitellogenesis. During blood digestion, ~ 10 mM heme-iron is ingested into the midgut lumen. While heme acts as both...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-020-06981-5
更新日期:2020-08-31 00:00:00
abstract:BACKGROUND:Helicobacter pylori is presumed to be co-evolved with its human host and is a highly diverse gastric pathogen at genetic levels. Ancient origins of H. pylori in the New World are still debatable. It is not clear how different waves of human migrations in South America contributed to the evolution of strain d...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-7-191
更新日期:2006-07-27 00:00:00
abstract:BACKGROUND:The freshwater planarian Schmidtea mediterranea is recognised as a valuable model for research into adult stem cells and regeneration. With the advent of the high-throughput sequencing technologies, it has become feasible to undertake detailed transcriptional analysis of its unique stem cell population, the ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-015-1533-1
更新日期:2015-05-08 00:00:00
abstract:BACKGROUND:Major secondary metabolites, including flavonoids, caffeine, and theanine, are important components of tea products and are closely related to the taste, flavor, and health benefits of tea. Secondary metabolite biosynthesis in Camellia sinensis is differentially regulated in different tissues during growth a...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-015-1773-0
更新日期:2015-07-29 00:00:00
abstract:BACKGROUND:RNA-Seq is now widely used as a research tool. Choices must be made whether to use paired-end (PE) or single-end (SE) sequencing, and whether to use strand-specific or non-specific (NS) library preparation kits. To date there has been no analysis of the effect of these choices on identifying differentially e...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-017-3797-0
更新日期:2017-05-23 00:00:00
abstract:BACKGROUND:Ras-related proteins in brain (Rab)-family proteins are key members of the membrane trafficking pathway in cells. In addition, these proteins have been identified to have diverse functions such as cross-talking with different kinases and playing a role in cellular signaling. However, only a few Rab proteins ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-016-3145-9
更新日期:2016-10-10 00:00:00
abstract:BACKGROUND:Transporter proteins are one of an organism's primary interfaces with the environment. The expressed set of transporters mediates cellular metabolic capabilities and influences signal transduction pathways and regulatory networks. The functional annotation of most transporters is currently limited to general...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-12-S1-S8
更新日期:2011-06-15 00:00:00
abstract:BACKGROUND:Wild sugarcane Saccharum spontaneum plants vary in ploidy, which complicates the utilization of its germplasm in sugarcane breeding. Investigations on cold tolerance in relation to different ploidies in S. spontaneum may promote the exploitation of its germplasm and accelerate the improvement of sugarcane va...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-020-06917-z
更新日期:2020-07-22 00:00:00
abstract:BACKGROUND:Sugarcane is an economically important crop contributing to about 80% of the world sugar production. Increasing efforts in molecular biological studies have been performed for improving the sugar yield and other relevant important agronomic traits. However, due to sugarcane's complicated genomes, it is still...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-016-2419-6
更新日期:2016-02-01 00:00:00
abstract:BACKGROUND:Many species of the genus Prevotella are pathogens that cause oral diseases. Prevotella intermedia is known to cause various oral disorders e.g. periodontal disease, periapical periodontitis and noma as well as colonize in the respiratory tract and be associated with cystic fibrosis and chronic bronchitis. I...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-015-1272-3
更新日期:2015-02-25 00:00:00
abstract:BACKGROUND:The host response to influenza A infections is strongly influenced by host genetic factors. Animal models of genetically diverse mouse strains are well suited to identify host genes involved in severe pathology, viral replication and immune responses. Here, we have utilized a dual RNAseq approach that allowe...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-015-1867-8
更新日期:2015-09-02 00:00:00
abstract:BACKGROUND:Bacterial phenotype may be profoundly affected by the physical arrangement of their genes in the genome. The Gram-negative species Aggregatibacter actinomycetemcomitans is a major etiologic agent of human periodontitis. Individual clonal types of A. actinomycetemcomitans may exhibit variable virulence and di...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-11-489
更新日期:2010-09-08 00:00:00
abstract:BACKGROUND:Papain-like cysteine proteases (PLCPs), a large group of cysteine proteases structurally related to papain, play important roles in plant development, senescence, and defense responses. Papain, the first cysteine protease whose structure was determined by X-ray crystallography, plays a crucial role in protec...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-017-4394-y
更新日期:2018-01-06 00:00:00
abstract:BACKGROUND:V(D)J recombinations in lymphocytes are essential for immunological diversity. They are also useful markers of pathologies. In leukemia, they are used to quantify the minimal residual disease during patient follow-up. However, the full breadth of lymphocyte diversity is not fully understood. RESULTS:We prop...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-15-409
更新日期:2014-05-28 00:00:00
abstract:BACKGROUND:Diversification on the basis of utilization is a hallmark of Beta vulgaris (beet), as well as other crop species. Often, crop improvement and management activities are segregated by crop type, thus preserving unique genome diversity and organization. Full interfertility is typically retained in crosses betwe...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-020-6451-1
更新日期:2020-03-02 00:00:00
abstract:BACKGROUND:The Gram-negative bacterium Chlamydia pneumoniae (Cpn) is the leading intracellular human pathogen responsible for respiratory infections such as pneumonia and bronchitis. Basic and applied research in pathogen biology, especially the elaboration of new mechanism-based anti-pathogen strategies, target discov...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-13-632
更新日期:2012-11-16 00:00:00
abstract:BACKGROUND:Genome-wide association studies have revealed associations between single-nucleotide polymorphisms (SNPs) and phenotypes such as disease symptoms and drug tolerance. To address the small sample size for rare variants, association studies tend to group gene or pathway level variants and evaluate the effect on...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-016-3094-3
更新日期:2016-09-21 00:00:00
abstract:BACKGROUND:Genome-scale metabolic models (GSMM) integrating transcriptomics have been widely used to study cancer metabolism. This integration is achieved through logical rules that describe the association between genes, proteins, and reactions (GPRs). However, current gene-to-reaction formulation lacks the stoichiome...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-019-5979-4
更新日期:2019-08-15 00:00:00
abstract:BACKGROUND:Cultivated peanut (Arachis hypogaea) is an allotetraploid species whose ancestral genomes are most likely derived from the A-genome species, A. duranensis, and the B-genome species, A. ipaensis. The very recent (several millennia) evolutionary origin of A. hypogaea has imposed a bottleneck for allelic and ph...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-13-469
更新日期:2012-09-11 00:00:00
abstract:BACKGROUND:The microsporidian Encephalitozoon cuniculi is an obligate intracellular eukaryotic pathogen with a small nuclear genome (2.9 Mbp) consisting of 11 chromosomes. Although each chromosome end is known to contain a single rDNA unit, the incomplete assembly of subtelomeric regions following sequencing of the gen...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-015-1920-7
更新日期:2016-01-07 00:00:00
abstract:BACKGROUND:As an important nosocomial pathogen, Enterococcus faecium has received increasing attention in recent years. However, a large number of studies have focused on the hospital-associated isolates and ignored isolates originated from the natural environments. RESULTS:In this study, comparative genomic analysis ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-019-5975-8
更新日期:2019-07-22 00:00:00
abstract:BACKGROUND:Systems biology and functional genomics require genome-wide datasets and resources. Complete sets of cloned open reading frames (ORFs) have been made for about a dozen bacterial species and allow researchers to express and study complete proteomes in a high-throughput fashion. RESULTS:We have constructed an...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-11-470
更新日期:2010-08-11 00:00:00
abstract:BACKGROUND:The superior temporal gyrus (STG), which encompasses the primary auditory cortex, is believed to be a major anatomical substrate for speech, language and communication. The STG connects to the limbic system (hippocampus and amygdala), the thalamus and neocortical association areas in the prefrontal cortex, a...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-9-199
更新日期:2008-04-29 00:00:00
abstract:BACKGROUND:Milkweeds (Asclepias L.) have been extensively investigated in diverse areas of evolutionary biology and ecology; however, there are few genetic resources available to facilitate and compliment these studies. This study explored how low coverage genome sequencing of the common milkweed (Asclepias syriaca L.)...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-12-211
更新日期:2011-05-04 00:00:00
abstract:BACKGROUND:Bulbs of the ornamental flower Lilium pumilum enter a period of dormancy after flowering in spring, and require exposure to cold for a period of time in order to release dormancy. Previous studies focused mainly on anatomical, physiological and biochemical changes during dormancy release. There are no dorman...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-018-4536-x
更新日期:2018-03-14 00:00:00
abstract:BACKGROUND:Progress in genetics and breeding in pea still suffers from the limited availability of molecular resources. SNP markers that can be identified through affordable sequencing processes, without the need for prior genome reduction or a reference genome to assemble sequencing data would allow the discovery and ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-016-2447-2
更新日期:2016-02-18 00:00:00
abstract:BACKGROUND:Cultivated peanut (Arachis hypogaea L.) is an important oil and protein crop, but it has low disease resistance; therefore, it is important to reveal the number, sequence features, function, and evolution of genes that confer resistance. Nucleotide-binding site-leucine-rich repeats (NBS-LRRs) are resistance ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-019-6212-1
更新日期:2019-11-13 00:00:00