The Impact of Pathway Database Choice on Statistical Enrichment Analysis and Predictive Modeling.

Abstract:

:Pathway-centric approaches are widely used to interpret and contextualize -omics data. However, databases contain different representations of the same biological pathway, which may lead to different results of statistical enrichment analysis and predictive models in the context of precision medicine. We have performed an in-depth benchmarking of the impact of pathway database choice on statistical enrichment analysis and predictive modeling. We analyzed five cancer datasets using three major pathway databases and developed an approach to merge several databases into a single integrative one: MPath. Our results show that equivalent pathways from different databases yield disparate results in statistical enrichment analysis. Moreover, we observed a significant dataset-dependent impact on the performance of machine learning models on different prediction tasks. In some cases, MPath significantly improved prediction performance and also reduced the variance of prediction performances. Furthermore, MPath yielded more consistent and biologically plausible results in statistical enrichment analyses. In summary, this benchmarking study demonstrates that pathway database choice can influence the results of statistical enrichment analysis and predictive modeling. Therefore, we recommend the use of multiple pathway databases or integrative ones.

journal_name

Front Genet

journal_title

Frontiers in genetics

authors

Mubeen S,Hoyt CT,Gemünd A,Hofmann-Apitius M,Fröhlich H,Domingo-Fernández D

doi

10.3389/fgene.2019.01203

subject

Has Abstract

pub_date

2019-11-22 00:00:00

pages

1203

issn

1664-8021

journal_volume

10

pub_type

杂志文章
  • Immunohistochemical Evaluation of Histological Change in a Chinese Milroy Disease Family With Venous and Skin Abnormities.

    abstract::Background: Milroy disease (MD) is rare and autosomal dominant resulting from mutations of the vascular endothelial growth factor receptor-3 (VEGFR-3 or FLT4), which leads to dysgenesis of the lymphatic system. Methods: Here we report a Chinese MD family with 2 affected members of two generations. We identified the mu...

    journal_title:Frontiers in genetics

    pub_type:

    doi:10.3389/fgene.2019.00206

    authors: Zhang S,Chen X,Yuan L,Wang S,Moli D,Liu S,Wu Y

    更新日期:2019-03-19 00:00:00

  • Phthalate Exposure and Long-Term Epigenomic Consequences: A Review.

    abstract::Phthalates are esters of phthalic acid which are used in cosmetics and other daily personal care products. They are also used in polyvinyl chloride (PVC) plastics to increase durability and plasticity. Phthalates are not present in plastics by covalent bonds and thus can easily leach into the environment and enter the...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章,评审

    doi:10.3389/fgene.2020.00405

    authors: Dutta S,Haggerty DK,Rappolee DA,Ruden DM

    更新日期:2020-05-06 00:00:00

  • Y-STR Haplogroup Diversity in the Jat Population Reveals Several Different Ancient Origins.

    abstract::The Jats represent a large ethnic community that has inhabited the northwest region of India and Pakistan for several thousand years. It is estimated the community has a population of over 123 million people. Many historians and academics have asserted that the Jats are descendants of Aryans, Scythians, or other ancie...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2017.00121

    authors: Mahal DG,Matsoukas IG

    更新日期:2017-09-20 00:00:00

  • Draft Genome and Complete Hox-Cluster Characterization of the Sterlet (Acipenser ruthenus).

    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

    authors: Cheng P,Huang Y,Du H,Li C,Lv Y,Ruan R,Ye H,Bian C,You X,Xu J,Liang X,Shi Q,Wei Q

    更新日期:2019-09-05 00:00:00

  • Programmable Base Editing of the Sheep Genome Revealed No Genome-Wide Off-Target Mutations.

    abstract::Since its emergence, CRISPR/Cas9-mediated base editors (BEs) with cytosine deaminase activity have been used to precisely and efficiently introduce single-base mutations in genomes, including those of human cells, mice, and crop species. Most production traits in livestock are induced by point mutations, and genome ed...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.00215

    authors: Zhou S,Cai B,He C,Wang Y,Ding Q,Liu J,Liu Y,Ding Y,Zhao X,Li G,Li C,Yu H,Kou Q,Niu W,Petersen B,Sonstegard T,Ma B,Chen Y,Wang X

    更新日期:2019-03-15 00:00:00

  • DNA Methylation Patterns of a Satellite Non-coding Sequence - FA-SAT in Cancer Cells: Its Expression Cannot Be Explained Solely by DNA Methylation.

    abstract::Satellite ncRNAs are emerging as key players in cell and cancer pathways. Cancer-linked satellite DNA hypomethylation seems to be responsible for the overexpression of satellite non-coding DNAs in several tumors. FA-SAT is the major satellite DNA of Felis catus and recently, its presence and transcription was describe...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.00101

    authors: Ferreira D,Escudeiro A,Adega F,Chaves R

    更新日期:2019-02-12 00:00:00

  • Identification and Analysis of the GASR Gene Family in Common Wheat (Triticum aestivum L.) and Characterization of TaGASR34, a Gene Associated With Seed Dormancy and Germination.

    abstract::Seed dormancy and germination are important agronomic traits in wheat (Triticum aestivum L.) because they determine pre-harvest sprouting (PHS) resistance and thus affect grain production. These processes are regulated by Gibberellic Acid-Stimulated Regulator (GASR) genes. In this study, we identified 37 GASR genes in...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.00980

    authors: Cheng X,Wang S,Xu D,Liu X,Li X,Xiao W,Cao J,Jiang H,Min X,Wang J,Zhang H,Chang C,Lu J,Ma C

    更新日期:2019-10-18 00:00:00

  • The obesity epidemic: from the environment to epigenetics - not simply a response to dietary manipulation in a thermoneutral environment.

    abstract::The prevalence of obesity continues to increase particularly in developed countries. To establish the primary mechanisms involved, relevant animal models which track the developmental pathway to obesity are required. This need is emphasized by the substantial rise in the number of overweight and obese children, of whi...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2011.00024

    authors: Symonds ME,Sebert S,Budge H

    更新日期:2011-05-31 00:00:00

  • Using Integrative Analysis of DNA Methylation and Gene Expression Data in Multiple Tissue Types to Prioritize Candidate Genes for Drug Development in Obesity.

    abstract::Obesity has become a major public health issue which is caused by a combination of genetic and environmental factors. Genome-wide DNA methylation studies have identified that DNA methylation at Cytosine-phosphate-Guanine (CpG) sites are associated with obesity. However, subsequent functional validation of the results ...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2018.00663

    authors: Guo Q,Zheng R,Huang J,He M,Wang Y,Guo Z,Sun L,Chen P

    更新日期:2018-12-19 00:00:00

  • Rare or Overlooked? Structural Disruption of Regulatory Domains in Human Neurocristopathies.

    abstract::In the last few years, the role of non-coding regulatory elements and their involvement in human disease have received great attention. Among the non-coding regulatory sequences, enhancers are particularly important for the proper establishment of cell type-specific gene-expression programs. Furthermore, the disruptio...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章,评审

    doi:10.3389/fgene.2020.00688

    authors: Sánchez-Gaya V,Mariner-Faulí M,Rada-Iglesias A

    更新日期:2020-07-20 00:00:00

  • The Integrative Regulatory Network of circRNA, microRNA, and mRNA in Atrial Fibrillation.

    abstract::Atrial fibrillation (AF) is the most common irregular heart rhythm which influence approximately 1-2% of the general population. As a potential factor for ischemic stroke, AF could also cause heart failure. The mechanisms behind AF pathogenesis is complex and remains elusive. As a new category of non-coding RNAs (ncRN...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.00526

    authors: Jiang S,Guo C,Zhang W,Che W,Zhang J,Zhuang S,Wang Y,Zhang Y,Liu B

    更新日期:2019-06-13 00:00:00

  • Recombinant Chromosomes Resulting From Parental Pericentric Inversions-Two New Cases and a Review of the Literature.

    abstract::A balanced pericentric inversion is normally without any clinical consequences for its carrier. However, there is a well-known risk of such inversions to lead to unbalanced offspring. Inversion-loop formation is the mechanism which may lead to duplication or deletion of the entire or parts of the inverted segment in t...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.01165

    authors: Liehr T,Weise A,Mrasek K,Ziegler M,Padutsch N,Wilhelm K,Al-Rikabi A

    更新日期:2019-11-14 00:00:00

  • The Active Constituent From Gynostemma Pentaphyllum Prevents Liver Fibrosis Through Regulation of the TGF-β1/NDRG2/MAPK Axis.

    abstract::Liver fibrosis resulting from chronic liver damage constitutes a major health care burden worldwide; however, no antifibrogenic agents are currently available. Our previous study reported that the small molecule NPLC0393 extracted from the herb Gynostemma pentaphyllum exerts efficient antifibrotic effects both in vivo...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.594824

    authors: Huang H,Wang K,Liu Q,Ji F,Zhou H,Fang S,Zhu J

    更新日期:2020-11-04 00:00:00

  • Circular RNA circSVIL Promotes Myoblast Proliferation and Differentiation by Sponging miR-203 in Chicken.

    abstract::Circular RNAs (circRNAs), expressed abundantly and universally in various eukaryotes, are involved in growth and development of animals. Our previous study on circRNA sequencing revealed that circSVIL, an exonic circular, expressed differentially among skeletal muscle at 11 embryo age (E11), 16 embryo age (E16), and 1...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2018.00172

    authors: Ouyang H,Chen X,Li W,Li Z,Nie Q,Zhang X

    更新日期:2018-05-16 00:00:00

  • DRIM: A Web-Based System for Investigating Drug Response at the Molecular Level by Condition-Specific Multi-Omics Data Integration.

    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 ...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.564792

    authors: Oh M,Park S,Lee S,Lee D,Lim S,Jeong D,Jo K,Jung I,Kim S

    更新日期:2020-11-12 00:00:00

  • Function and evolution of microRNAs in eusocial Hymenoptera.

    abstract::The emergence of eusociality ("true sociality") in several insect lineages represents one of the most successful evolutionary adaptations in the animal kingdom in terms of species richness and global biomass. In contrast to solitary insects, eusocial insects evolved a set of unique behavioral and physiological traits ...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2015.00193

    authors: Søvik E,Bloch G,Ben-Shahar Y

    更新日期:2015-05-27 00:00:00

  • Genetic analysis of long-lived families reveals novel variants influencing high density-lipoprotein cholesterol.

    abstract::The plasma levels of high-density lipoprotein cholesterol (HDL) have an inverse relationship to the risks of atherosclerosis and cardiovascular disease (CVD), and have also been associated with longevity. We sought to identify novel loci for HDL that could potentially provide new insights into biological regulation of...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2014.00159

    authors: Feitosa MF,Wojczynski MK,Straka R,Kammerer CM,Lee JH,Kraja AT,Christensen K,Newman AB,Province MA,Borecki IB

    更新日期:2014-06-03 00:00:00

  • Photoprotective Acclimation of the Arabidopsis thaliana Leaf Proteome to Fluctuating Light.

    abstract::Plants are subjected to strong fluctuations in light intensity in their natural growth environment, caused both by unpredictable changes due to weather conditions and movement of clouds and upper canopy leaves and predictable changes during day-night cycle. The mechanisms of long-term acclimation to fluctuating light ...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.00154

    authors: Niedermaier S,Schneider T,Bahl MO,Matsubara S,Huesgen PF

    更新日期:2020-03-05 00:00:00

  • Association of Fibroblast Growth Factor 23 With Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study.

    abstract::Fibroblast growth factor 23 (FGF23), which is involved in the regulation of vitamin D, is an emerging independent risk factor for cardiovascular diseases. Previous studies have demonstrated a positive association between FGF23 and stroke. In this study, we aimed to assess the association of FGF23 with ischemic stroke ...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.608517

    authors: Zheng K,Lin L,Cui P,Liu T,Chen L,Yang C,Jiang W

    更新日期:2020-12-23 00:00:00

  • S100A6 Promotes B Lymphocyte Penetration Through the Blood-Brain Barrier in Autoimmune Encephalitis.

    abstract::Autoimmune encephalitis (AE) is a severe neurological disease. The brain of the AE patient is attacked by a dysregulated immune system, which is caused by the excessive production of autoantibodies against neuronal receptors and synaptic proteins. AE is also characterized by the uncontrolled B lymphocyte infiltration ...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.01188

    authors: Tsai MH,Lin CH,Tsai KW,Lin MH,Ho CJ,Lu YT,Weng KP,Lin Y,Lin PH,Li SC

    更新日期:2019-11-22 00:00:00

  • Mechanisms Underlying the Environmentally Induced Plasticity of Leaf Morphology.

    abstract::The primary function of leaves is to provide an interface between plants and their environment for gas exchange, light exposure and thermoregulation. Leaves have, therefore a central contribution to plant fitness by allowing an efficient absorption of sunlight energy through photosynthesis to ensure an optimal growth....

    journal_title:Frontiers in genetics

    pub_type: 杂志文章,评审

    doi:10.3389/fgene.2018.00478

    authors: Fritz MA,Rosa S,Sicard A

    更新日期:2018-10-24 00:00:00

  • Identification of Potential Long Non-coding RNA Expression Quantitative Trait Methylations in Lung Adenocarcinoma and Lung Squamous Carcinoma.

    abstract::There are associations between DNA methylation and the expression of long non-coding RNA (lncRNA), also known as lncRNA expression quantitative trait methylations (lnc-eQTMs). Lnc-eQTMs may induce a wide range of carcinogenesis pathways. However, lnc-eQTMs have not been globally identified and studied, and their roles...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.602035

    authors: Wu X,Gao Y,Bu J,Deng L,Zhang P,Chi M,Jiang L,Shi X,Ning S,Wang G

    更新日期:2020-12-09 00:00:00

  • The Trp73 Mutant Mice: A Ciliopathy Model That Uncouples Ciliogenesis From Planar Cell Polarity.

    abstract::p73 transcription factor belongs to one of the most important gene families in vertebrate biology, the p53-family. Trp73 gene, like the other family members, generates multiple isoforms named TA and DNp73, with different and, sometimes, antagonist functions. Although p73 shares many biological functions with p53, it a...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章,评审

    doi:10.3389/fgene.2019.00154

    authors: Marques MM,Villoch-Fernandez J,Maeso-Alonso L,Fuertes-Alvarez S,Marin MC

    更新日期:2019-03-15 00:00:00

  • Lost in Translation: Ribosome-Associated mRNA and Protein Quality Controls.

    abstract::Aberrant, misfolded, and mislocalized proteins are often toxic to cells and result in many human diseases. All proteins and their mRNA templates are subject to quality control. There are several distinct mechanisms that control the quality of mRNAs and proteins during translation at the ribosome. mRNA quality control ...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章,评审

    doi:10.3389/fgene.2018.00431

    authors: Karamyshev AL,Karamysheva ZN

    更新日期:2018-10-04 00:00:00

  • Comparing Genomic Signatures of Selection Between the Abbassa Strain and Eight Wild Populations of Nile Tilapia (Oreochromis niloticus) in Egypt.

    abstract::Domestication to captive rearing conditions, along with targeted selective breeding have genetic consequences that vary from those in wild environments. Nile tilapia (Oreochromis niloticus) is one of the most translocated and farmed aquaculture species globally, farmed throughout Asia, North and South America, and its...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.567969

    authors: Nayfa MG,Jones DB,Benzie JAH,Jerry DR,Zenger KR

    更新日期:2020-10-15 00:00:00

  • Fine-tuning the ubiquitin code at DNA double-strand breaks: deubiquitinating enzymes at work.

    abstract::Ubiquitination is a reversible protein modification broadly implicated in cellular functions. Signaling processes mediated by ubiquitin (ub) are crucial for the cellular response to DNA double-strand breaks (DSBs), one of the most dangerous types of DNA lesions. In particular, the DSB response critically relies on act...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章,评审

    doi:10.3389/fgene.2015.00282

    authors: Citterio E

    更新日期:2015-09-08 00:00:00

  • Lifetime Smoking and Asthma: A Mendelian Randomization Study.

    abstract::Evidence from clinical and epidemiological studies indicates that asthma is associated with allergic diseases including hay fever, allergic rhinitis, and eczema. Genetic analysis demonstrated that asthma had a positive genetic correlation with allergic diseases. A Mendelian randomization (MR) analysis using the rs1696...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.00769

    authors: Shen M,Liu X,Li G,Li Z,Zhou H

    更新日期:2020-08-04 00:00:00

  • Gene and Protein Expression in Subjects With a Nystagmus-Associated AHR Mutation.

    abstract::Recently, a consanguineous family was identified in Israel with three children affected by Infantile Nystagmus and Foveal Hypoplasia, following an autosomal recessive mode of inheritance. A homozygous stop mutation c.1861C > T; p.Q621∗ in the aryl hydrocarbon receptor (AHR) gene (AHR; MIM 600253) was identified that c...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.582796

    authors: Borovok N,Weiss C,Sharkia R,Reichenstein M,Wissinger B,Azem A,Mahajnah M

    更新日期:2020-09-24 00:00:00

  • Epigenetic Modifications in Acute Myeloid Leukemia: Prognosis, Treatment, and Heterogeneity.

    abstract::Leukemia, specifically acute myeloid leukemia (AML), is a common malignancy that can be differentiated into multiple subtypes based on leukemogenic history and etiology. Although genetic aberrations, particularly cytogenetic abnormalities and mutations in known oncogenes, play an integral role in AML development, epig...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章,评审

    doi:10.3389/fgene.2019.00133

    authors: Goldman SL,Hassan C,Khunte M,Soldatenko A,Jong Y,Afshinnekoo E,Mason CE

    更新日期:2019-03-01 00:00:00

  • Regular exercise, subjective wellbeing, and internalizing problems in adolescence: causality or genetic pleiotropy?

    abstract::This study tests in a genetically informative design whether exercise behavior causally influences subjective wellbeing (SWB) and internalizing problems (INT). If exercise causally influences SWB and INT, genetic and environmental factors influencing exercise behavior will also influence SWB and INT. Furthermore, with...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2012.00004

    authors: Bartels M,de Moor MH,van der Aa N,Boomsma DI,de Geus EJ

    更新日期:2012-01-19 00:00:00