Abstract:
:Pharmacogenomics is the study of how genes affect a person's response to drugs. Thus, understanding the effect of drug at the molecular level can be helpful in both drug discovery and personalized medicine. Over the years, transcriptome data upon drug treatment has been collected and several databases compiled before drug treatment cancer cell multi-omics data with drug sensitivity (IC50, AUC) or time-series transcriptomic data after drug treatment. However, analyzing transcriptome data upon drug treatment is challenging since more than 20,000 genes interact in complex ways. In addition, due to the difficulty of both time-series analysis and multi-omics integration, current methods can hardly perform analysis of databases with different data characteristics. One effective way is to interpret transcriptome data in terms of well-characterized biological pathways. Another way is to leverage state-of-the-art methods for multi-omics data integration. In this paper, we developed Drug Response analysis Integrating Multi-omics and time-series data (DRIM), an integrative multi-omics and time-series data analysis framework that identifies perturbed sub-pathways and regulation mechanisms upon drug treatment. The system takes drug name and cell line identification numbers or user's drug control/treat time-series gene expression data as input. Then, analysis of multi-omics data upon drug treatment is performed in two perspectives. For the multi-omics perspective analysis, IC50-related multi-omics potential mediator genes are determined by embedding multi-omics data to gene-centric vector space using a tensor decomposition method and an autoencoder deep learning model. Then, perturbed pathway analysis of potential mediator genes is performed. For the time-series perspective analysis, time-varying perturbed sub-pathways upon drug treatment are constructed. Additionally, a network involving transcription factors (TFs), multi-omics potential mediator genes, and perturbed sub-pathways is constructed, and paths to perturbed pathways from TFs are determined by an influence maximization method. To demonstrate the utility of our system, we provide analysis results of sub-pathway regulatory mechanisms in breast cancer cell lines of different drug sensitivity. DRIM is available at: http://biohealth.snu.ac.kr/software/DRIM/.
journal_name
Front Genetjournal_title
Frontiers in geneticsauthors
Oh M,Park S,Lee S,Lee D,Lim S,Jeong D,Jo K,Jung I,Kim Sdoi
10.3389/fgene.2020.564792subject
Has Abstractpub_date
2020-11-12 00:00:00pages
564792issn
1664-8021journal_volume
11pub_type
杂志文章abstract:Background:Recent evidence has indicated that long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) to modulate mRNAs expression by sponging microRNAs (miRNAs). However, the specific mechanism and function of lncRNA-miRNA-mRNA regulatory network in non-small cell lung cancer (NSCLC) remains ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.511676
更新日期:2020-09-18 00:00:00
abstract::Recent advances in genomics and proteomics generated a large amount of trans regulatory data such as those mediated by RNA binding proteins (RBPs) and microRNAs. Since many trans regulators target 3' UTR of mRNA transcripts, it is likely that there would be interactions, i.e., competitive or cooperative effect, among ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.515094
更新日期:2020-09-08 00:00:00
abstract::Over millions of years, vertebrate species populated vast environments spanning the globe. Among the most challenging habitats encountered were those with limited availability of oxygen, yet many animal and human populations inhabit and perform life cycle functions and/or daily activities in varying degrees of hypoxia...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2020.00743
更新日期:2020-07-22 00:00:00
abstract::A variety of statistical methods, such as admixture models, have been used to estimate genomic breed composition (GBC). These methods, however, tend to produce non-zero components to reference breeds that shared some genomic similarity with a test animal. These non-essential GBC components, in turn, offset the estimat...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00576
更新日期:2020-06-11 00:00:00
abstract::Genome-wide association study (GWAS), exploring the historical and evolutionary recombinations at the population level, is a major method adopted to identify quantitative trait loci (QTL) for complex traits. However, to summarize GWAS results, gene structure, and linkage disequilibrium (LD) in a single view, multiple ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00260
更新日期:2020-03-20 00:00:00
abstract::Single variant analysis in genome-wide association studies (GWAS) has been proven to be successful in identifying thousands of genetic variants associated with hundreds of complex diseases. However, these identified variants only explain a small fraction of inheritable variability in many diseases, suggesting that oth...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00395
更新日期:2014-11-12 00:00:00
abstract::Fragile-X syndrome is one of the most common forms of inherited mental retardation and autistic behaviors. The reduction/absence of the functional FMRP protein, coded by the X-linked Fmr1 gene in humans, is responsible for the syndrome. Patients exhibit a variety of symptoms predominantly linked to the function of FMR...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2019.00010
更新日期:2019-02-13 00:00:00
abstract::Poultry feed constitutes the largest cost in poultry production, estimated to be up to 70% of the total cost. Moreover, there is pressure on the poultry industry to increase production to meet the protein demand of humans and simultaneously reduce emissions to protect the environment. Therefore, improving feed efficie...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00243
更新日期:2020-04-03 00:00:00
abstract::Alport syndrome (AS) is a rare and inherited renal disorder with an autosomal recessive mode of inheritance. AS patients usually manifest with hematuria and progressive renal disorder also occasionally accompanied by hearing loss and ophthalmic disease. Germline variants in collagen type IV α-4 (COL4A4) gene lead to a...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00748
更新日期:2019-01-28 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disease that affects millions of individuals worldwide and can occur relatively early or later in life. It is well known that genetic components, such as the amyloid precursor protein gene on chromosome 21, are fundamental in early-onset AD (EOAD). To date, however, only...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2019.01368
更新日期:2020-01-28 00:00:00
abstract::Epithelial ovarian cancer (EOC) is one of the malignancies in women, which has the highest mortality. However, the microlevel mechanism has not been discussed in detail. The expression profiles GSE27651, GSE38666, GSE40595, and GSE66957 including 188 tumor and 52 nontumor samples were downloaded from the Gene Expressi...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.01031
更新日期:2019-10-24 00:00:00
abstract::Goats (Capra hircus) are an economically important livestock species providing meat and milk across the globe. They are of particular importance in tropical agri-systems contributing to sustainable agriculture, alleviation of poverty, social cohesion, and utilisation of marginal grazing. There are excellent genetic an...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.01080
更新日期:2019-11-04 00:00:00
abstract::Our ability to overcome the challenges behind metabolic disorders will require a detailed understanding of the regulation of responses to nutrition. The Creb3 transcription factor family appears to have a unique regulatory role that links cellular secretory capacity with development, nutritional state, infection, and ...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2019.00591
更新日期:2019-06-21 00:00:00
abstract:Background:SOX2 overlapping transcript (SOX2-OT) produces alternatively spliced long non-coding RNAs (lncRNA). Previous studies of the prognostic role of SOX2-OT expression met with conflicting results. The aim of this study was to properly consider the prognostic role of SOX2-OT expression in several cancers. In addit...
journal_title:Frontiers in genetics
pub_type:
doi:10.3389/fgene.2019.01375
更新日期:2020-01-23 00:00:00
abstract::Long non-coding RNAs (lncRNAs) are an emerging class of RNA species that may play a critical regulatory role in gene expression. However, the association between lncRNAs and atrial fibrillation (AF) is still not fully understood. In this study, we used RNA sequencing data to identify and quantify the both protein codi...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00908
更新日期:2019-10-02 00:00:00
abstract::Postpartum depression (PPD) affects up to 19% of women, negatively impacting maternal and infant health. Reductions in plasma oxytocin levels have been associated with PPD and heritability studies have established a genetic contribution. Epigenetic regulation of the oxytocin receptor gene (OXTR) has been demonstrated ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2015.00243
更新日期:2015-07-21 00:00:00
abstract::Reliability of genomic selection (GS) models was tested in an admixed population of Atlantic salmon, originating from crossing of several wild subpopulations. The models included ordinary genomic BLUP models (GBLUP), using genome-wide SNP markers of varying densities (1-220 k), a genomic identity-by-descent model (IBD...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00402
更新日期:2014-11-21 00:00:00
abstract::In the last 40 years, the Asian tiger mosquito Aedes albopictus, indigenous to East Asia, has colonized every continent except Antarctica. Its spread is a major public health concern, given that this species is a competent vector for numerous arboviruses, including those causing dengue, chikungunya, West Nile, and the...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2016.00208
更新日期:2016-11-23 00:00:00
abstract::One of the challenges in the analysis of large data sets, particularly in a population-based setting, is the ability to perform comparisons across projects. This has to be done in such a way that the integrity of each individual project is maintained, while ensuring that the data are comparable across projects. These ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00325
更新日期:2014-09-18 00:00:00
abstract::We report on three new patients with spondyloocular syndrome (SOS) in a consanguineous Pakistani family. All three patients present progressive generalized osteoporosis, short stature, recurrent fractures, hearing loss and visual impairments. WES revealed a novel homozygous frameshift variant in exon 11 of XYLT2 (NG 0...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00144
更新日期:2019-03-05 00:00:00
abstract::The evolutionary dynamics and tissue specificity of protein-coding genes are well documented in plants. However, the evolutionary consequences of small RNAs (sRNAs) on tissue-specific functions remain poorly understood. Here, we performed integrated analysis of 195 deeply sequenced sRNA libraries of maize B73, represe...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00051
更新日期:2020-02-11 00:00:00
abstract::Germline variants of PIP4K2A impact susceptibility of acute lymphoblastic leukemia (ALL) through inducing its overexpression. Although limited reports suggested the oncogenic role of PIP4K2A in cancers, regulatory network and prognostic effect of this gene remains poorly understood in tumorigenesis and leukemogenesis....
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00721
更新日期:2019-01-15 00:00:00
abstract::Mechanotransduction is an essential mechanism of transforming external mechanical stimulus to biochemical response. In cardiomyocytes mechanotransduction plays an important role in contraction, stretch sensing and homeostasis regulation. One of the major mechanosensitive area in cardiomyocytes, the Z-disk, consists of...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00684
更新日期:2019-01-07 00:00:00
abstract::Autism spectrum disorder (ASD) is marked by a strong genetic heterogeneity, which is underlined by the low overlap between ASD risk gene lists proposed in different studies. In this context, molecular networks can be used to analyze the results of several genome-wide studies in order to underline those network regions...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2017.00129
更新日期:2017-09-25 00:00:00
abstract::Variability of the comet assay is a serious issue, whether it occurs from experiment to experiment in the same laboratory, or between different laboratories analysing identical samples. Do we have to live with high variability, just because the comet assay is a biological assay rather than analytical chemistry? Numero...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00359
更新日期:2014-10-20 00:00:00
abstract::Pearl millet is a climate-resilient, drought-tolerant crop capable of growing in marginal environments of arid and semi-arid regions globally. Pearl millet is a staple food for more than 90 million people living in poverty and can address the triple burden of malnutrition substantially. It remained a neglected crop un...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2019.01389
更新日期:2020-02-28 00:00:00
abstract::The increased feasibility of whole-genome (or whole-exome) sequencing has led to renewed interest in using family data to find disease mutations. For clinical phenotypes that lend themselves to study in large families, this approach can be particularly effective, because it may be possible to obtain strong evidence of...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2013.00059
更新日期:2013-04-19 00:00:00
abstract::Background: Sturgeons (Chondrostei: Acipenseridae) are a group of "living fossil" fishes at a basal position among Actinopteri. They have raised great public interest due to their special evolutionary position, species conservation challenges, as well as their highly-prized eggs (caviar). The sterlet, Acipenser ruthen...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00776
更新日期:2019-09-05 00:00:00
abstract::Growing evidences have indicated that microRNAs (miRNAs) play a significant role relating to many important bioprocesses; their mutations and disorders will cause the occurrence of various complex diseases. The prediction of miRNAs associated with underlying diseases via computational approaches is beneficial to ident...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00389
更新日期:2020-04-30 00:00:00
abstract::RNA is a unique bio-macromolecule that can both record genetic information and perform biological functions in a variety of molecular processes, including transcription, splicing, translation, and even regulating protein function. RNAs adopt specific three-dimensional conformations to enable their functions. Experimen...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2020.574485
更新日期:2020-10-26 00:00:00