78 research outputs found
Abstract 3586: Comprehensive assessment of mouse contamination removal strategies from patient-derived xenograft model sequencing data
No full textAbstract
Patient-derived xenograft (PDX) models of human tumors are an important and widely used platform for cancer research. Cancer drug development relies on PDX models to screen drugs and characterize tumor biology for potential drug targets. It has been well established that PDX models maintain similar biology as their original tumors, including histological patterning, gene expression, single-nucleotide variants, and copy number alterations. Using short-read sequencing technology to profile and characterize genomic alterations within PDX tumor models is becoming a common practice in cancer research. Mouse read contamination is a relevant source of noise in PDX tumor sequencing data and needs to be addressed prior to downstream analyses. Therefore, a key consideration for downstream analysis of PDX sequencing data, such as determining variant calls or gene expression values, is effectively removing contaminating mouse sequence. Removing contamination from PDX sequencing data is necessary for accurate and reproducible downstream analyses. A limited number of studies establishing best practices for handling PDX sequencing data exist. Thus, we set out to compare different strategies for removing mouse contamination from PDX tumor sequencing data for DNA and RNA using a set of controlled experimental in silico datasets and data from PDX tumors.
We designed a set of in silico experiments using these sequencing data to assess a range of approaches for removing contaminating mouse reads from human data. Our experiments used a set of publically available human and mouse DNA and RNA sequencing data available at the SRA site. Subsets of the raw human and mouse reads were mixed at different ratios and analyzed with five different approaches: 1) raw alignment to the human reference genome, 2) filtering with the Xenome algorithm followed by alignment to the human genome, 3) alignment to the human reference genome followed by filtering with the XenofilteR algorithm, 4) mouse-human hybrid reference genome alignment, and 5) our novel NextCODE approach.
We assessed the sensitivity and specificity of each procedure for removing mouse sequence and maintaining human sequence for downstream analyses. We also assessed the effects of each filtering procedure on gene expression quantification and variant calling.
Our results introduce a novel, improved method for removing mouse DNA, facilitating better-quality data for downstream analysis.
Citation Format: Ryan P. Abo, Zehua Chen, Shannon Bailey, Hao Wang, Sharvari Gujja, Pengwei Yang, Jim Lund, Jeff Gulcher, Tom Chittenden. Comprehensive assessment of mouse contamination removal strategies from patient-derived xenograft model sequencing data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3586. doi:10.1158/1538-7445.AM2017-3586</jats:p
Active Vibration Control of Smart Structure Using PZT Patches
No full textAbstractThe assembly that serves an engineering function is called as structure and structure that exhibits intelligence, efficiency, adaptability, accurate response and optimum performance is termed as a smart structure. Though, due to these advantages smart structures are used in many high end applications like aerospace engineering, microelectronics productions, precise positioning and automation industries, active vibration control of these structures is extremely important. This is because; mechanical vibrations in the structure can have detrimental effects as they can damage sensitive components of the structure or even the whole structure. Vibration control basically suppresses the effect of external disturbances and keeps the structure in its equilibrium position. In this paper, vibration control analysis of the structure for forced vibrations is carried out. The smart structure considered here, is a finite and flat beam-like fiber cantilever structure with PZT patches attached to its surface. Along with vibration control analysis effect of changing positions of PZT patches on this analysis is also discussed in this paper
Cholesterol-Independent SREBP-1 Maturation Is Linked to ARF1 Inactivation
No full textLipogenesis requires coordinated expression of genes for fatty acid, phospholipid, and triglyceride synthesis. Transcription factors, such as SREBP-1 (Sterol regulatory element binding protein), may be activated in response to feedback mechanisms linking gene activation to levels of metabolites in the pathways. SREBPs can be regulated in response to membrane cholesterol and we also found that low levels of phosphatidylcholine (a methylated phospholipid) led to SBP-1/SREBP-1 maturation in C. elegans or mammalian models. To identify additional regulatory components, we performed a targeted RNAi screen in C. elegans, finding that both lpin-1/Lipin 1 (which converts phosphatidic acid to diacylglycerol) and arf-1.2/ARF1 (a GTPase regulating Golgi function) were important for low-PC activation of SBP-1/SREBP-1. Mechanistically linking the major hits of our screen, we find that limiting PC synthesis or LPIN1 knockdown in mammalian cells reduces the levels of active GTP-bound ARF1. Thus, changes in distinct lipid ratios may converge on ARF1 to increase SBP-1/SREBP-1 activity
Cholesterol-Independent SREBP-1 Maturation Is Linked to ARF1 Inactivation
No full textSummaryLipogenesis requires coordinated expression of genes for fatty acid, phospholipid, and triglyceride synthesis. Transcription factors, such as SREBP-1 (Sterol regulatory element binding protein), may be activated in response to feedback mechanisms linking gene activation to levels of metabolites in the pathways. SREBPs can be regulated in response to membrane cholesterol and we also found that low levels of phosphatidylcholine (a methylated phospholipid) led to SBP-1/SREBP-1 maturation in C. elegans or mammalian models. To identify additional regulatory components, we performed a targeted RNAi screen in C. elegans, finding that both lpin-1/Lipin 1 (which converts phosphatidic acid to diacylglycerol) and arf-1.2/ARF1 (a GTPase regulating Golgi function) were important for low-PC activation of SBP-1/SREBP-1. Mechanistically linking the major hits of our screen, we find that limiting PC synthesis or LPIN1 knockdown in mammalian cells reduces the levels of active GTP-bound ARF1. Thus, changes in distinct lipid ratios may converge on ARF1 to increase SBP-1/SREBP-1 activity
Gld2-catalyzed 3′ monoadenylation of miRNAs in the hippocampus has no detectable effect on their stability or on animal behavior
No full textGld2, a noncanonical cytoplasmic poly(A) polymerase, interacts with the RNA binding protein CPEB1 to mediate polyadenylation-induced translation in dendrites of cultured hippocampal neurons. Depletion of Gld2 from the hippocampus leads to a deficit in long-term potentiation evoked by theta burst stimulation. At least in mouse liver and human primary fibroblasts, Gld2 also 3' monoadenylates and thereby stabilizes specific miRNAs, which enhance mRNA translational silencing and eventual destruction. These results suggest that Gld2 would be likely to monoadenylate and stabilize miRNAs in the hippocampus, which would produce measurable changes in animal behavior. We now report that using Gld2 knockout mice, there are detectable alterations in specific miRNA monoadenylation in the hippocampus when compared to wild type, but that these modifications produce no detectable effect on miRNA stability. Moreover, we surprisingly find no overt change in animal behavior when comparing Gld2 knockout to wild-type mice. These data indicate that miRNA monoadenylation-mediated stability is cell type-specific and that monoadenylation has no measurable effect on higher cognitive function
Gld2-catalyzed 3′ monoadenylation of miRNAs in the hippocampus has no detectable effect on their stability or on animal behavior
No full textThe Basics of Big Data and Security Concerns
No full textThe chapter is written on two important buildings, the basics of Big data and their security concern. The chapter is classifying in different sections. The chapter starts with the basic of big data and is concluded with security concern. The chapter is enriched with different category examples to make texts easy for author understanding. The chapter begins with the introduction of big data, their memory size followed by the examples. The chapter explains the category of big data in type of structured, semi-structured and unstructured data. The discussion on operational data service and big data application is also included to ensure the basic understanding to readers. The second portion of chapter which is based on security in big data. It's explaining the issues and challenges in big data. The section also focusing on the shift paradigm from cloud environment to big data environment changes and the problems encounter by organizations. The section discusses the framework issue and concluded with the necessity of understanding security in the big data, keeping in view of expansion of information technology infrastructure in the 21st century. </jats:p
Unveiling the dynamics of farmer producer organizations in India: a systematic review of status, challenges, and future directions
No full textAbstract India, a developing country heavily reliant on the agricultural sector, has witnessed the emergence of farmer producer organizations (FPOs) as a transformative collective model for farmers as an alternative to traditional cooperatives. The FPOs aim to solve the problems encountered by small and marginal farmers, especially those about better access to capital, technical improvements, and efficient inputs and markets. A comprehensive review of the literature in this field is essential because of the rapid advancement of FPO research articles. Scholars have published several review articles on FPO from different perspectives to tackle this issue. However, there is not a considerable number of published studies on FPO that incorporate bibliometric analysis. In the present study, an attempt is made to investigate the FPO publications with bibliometric analysis. This study employs a systematic literature review methodology, focusing on research published between 2002 and 2023. From an initial pool of 3796 research articles, 64 relevant studies from the Scopus database were identified for the study. These papers were analyzed using publication, journal, country, and author productivity, as well as the highest cited documents, co-citation analysis, bibliographic coupling analysis, and cluster analysis. The findings reveal that most studies focus on assessing the performance of FPOs, with limited attention to critical areas like institutional support, leadership, and policy execution. The cluster analysis results revealed that agricultural marketing, sustainable agriculture, the impact of membership on performance, women in agriculture, manufacturing, sustainability driving innovation, and technological efficiency of the food supply chain are the emerging themes in the literature. This paper provides policy recommendations on some significant challenges FPOs face, such as streamlining documentation, enhancing market access, ensuring fair tax treatment, allowing fertilizer distribution rights, and promoting farmer-led leadership
Nat Genet
No full textWe sequenced and annotated the genomes of four P. vivax strains collected from disparate geographic locations, tripling the number of genome sequences available for this understudied parasite and providing the first genome-wide perspective of global variability in this species. We observe approximately twice as much SNP diversity among these isolates as we do among a comparable collection of isolates of P. falciparum, a malaria-causing parasite that results in higher mortality. This indicates a distinct history of global colonization and/or a more stable demographic history for P. vivax relative to P. falciparum, which is thought to have undergone a recent population bottleneck. The SNP diversity, as well as additional microsatellite and gene family variability, suggests a capacity for greater functional variation in the global population of P. vivax. These findings warrant a deeper survey of variation in P. vivax to equip disease interventions targeting the distinctive biology of this neglected but major pathogen.20122013-03-01T00:00:00ZU19 AI089676/AI/NIAID NIH HHS/United StatesHHSN272200900018C/AI/NIAID NIH HHS/United StatesHHSN272200900008C/AI/NIAID NIH HHS/United StatesU19AI089676/AI/NIAID NIH HHS/United StatesHHSN272200900001C/AI/NIAID NIH HHS/United StatesR01GM084320/GM/NIGMS NIH HHS/United StatesHHSN266200400001C/AO/NIAID NIH HHS/United StatesR01 GM084320/GM/NIGMS NIH HHS/United StatesR01 GM080586/GM/NIGMS NIH HHS/United States22863733PMC34327101152
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