“Super Gene Set” Causal Relationship Discovery from Functional Genomics Data

Yue, Zongliang; Neylon, Michael T.; Nguyen, Thanh; Ratliff, Timothy L.; Chen, Jake Y.

doi:10.1109/tcbb.2018.2858755

Cited by 4 publications

(5 citation statements)

References 36 publications

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“…Next, we tested the association between the DS pathway and other pathways enriched in MS based on the expression data. This reveals a regulatory relationship regardless of direct or indirect interactions between pathways [28]. We found quite a few pathways correlated with the DS pathway in either grey or white matter (Fig.…”

Section: Transcriptome Analysis Of Dopaminergic Gene Setsmentioning

confidence: 54%

“…To calculate the relationship between two gene sets, "Super Gene Set" causal relationship analysis was performed as previously described [28]. Gene expression values were discretized as follows: the highest 1/3 absolute gene expression was converted to +1, the lowest 1/3 absolute expression values were represented as -1, while the other 1/3 in between were assigned to 0.…”

Section: Gene Set Causal Relationship Analysismentioning

confidence: 99%

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Integrative systems and functional analyses reveal a role of dopaminergic signaling in myelin pathogenesis

Ding

Cai

et al. 2020

J Transl Med

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Background: Myelin sheaths surrounding axons are critical for electrical signal transmission in the central nervous system (CNS). Diseases with myelin defects such as multiple sclerosis (MS) are devastating neurological conditions for which few effective treatments are available. Dysfunction of the dopaminergic system has been observed in multiple neurological disorders. Its role in myelin pathogenesis, however, is unclear. Methods: This work used a combination of literature curation, bioinformatics, pharmacological and genetic manipulation, as well as confocal imaging techniques. Literature search was used to establish a complete set of genes which is associated with MS in humans. Bioinformatics analyses include pathway enrichment and crosstalk analyses with human genetic association studies as well as gene set enrichment and causal relationship analyses with transcriptome data. Pharmacological and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPRassociated protein 9) genetic manipulation were applied to inhibit the dopaminergic signaling in zebrafish. Imaging techniques were used to visualize myelin formation in vivo. Results: Systematic analysis of human genetic association studies revealed that the dopaminergic synapse signaling pathway is enriched in candidate gene sets. Transcriptome analysis confirmed that expression of multiple dopaminergic gene sets was significantly altered in patients with MS. Pathway crosstalk analysis and gene set causal relationship analysis reveal that the dopaminergic synapse signaling pathway interacts with or is associated with other critical pathways involved in MS. We also found that disruption of the dopaminergic system leads to myelin deficiency in zebrafish. Conclusions: Dopaminergic signaling may be involved in myelin pathogenesis. This study may offer a novel molecular mechanism of demyelination in the nervous system.

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Section: Transcriptome Analysis Of Dopaminergic Gene Setsmentioning

confidence: 54%

Section: Gene Set Causal Relationship Analysismentioning

confidence: 99%

Integrative systems and functional analyses reveal a role of dopaminergic signaling in myelin pathogenesis

Ding

Cai

et al. 2020

J Transl Med

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“…We found that cell adhesion pathways are enriched following administration of the dopamine Though evidence suggests that to some extent the levels of dopamine in platelets and urine is associated with symptoms of ASD (Launay et al 1987) (Clin 1992), and also that dopaminergic signaling has been shown to be associated with a wide range of developmental disorders, few studies have described the role of dopamine in producing developmental defects in ASD patients. We conducted causal relationship analysis of several key gene sets for dopaminergic signal transduction with the developmental gene sets of interest (Yue et al 2018). The results indicate that the dopamine gene set is strongly linked to the developmental gene set.…”

Section: Discussionmentioning

confidence: 99%

“…"Super Gene Set" causal relationship analysis was conducted to determine the relationship between two selected gene sets (Yue et al 2018). Gene expression values were discretized: the highest 1/3, lowest 1/3, and the middle 1/3 were assigned to 1, -1, and 0, respectively.…”

Section: Gene Set Causal Relationship Analysismentioning

confidence: 99%

Dopaminergic signaling is linked to neurodevelopmental deficits in autism spectrum disorder (ASD)

Wang

Chai

Lin

et al. 2022

Preprint

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Neural circuit defects are a prominent feature of autism spectrum disorder (ASD). However, the specific defects in neural circuits and the resulting pathogenesis are not well understood. We conducted a systematic analysis of two ASD datasets and found alterations in multiple neurodevelopmental pathways and in dopaminergic signaling pathways. Interestingly, the dopaminergic signaling pathways are associated with neurodevelopmental pathways in patients with ASD. We also discovered that disruption of the dopaminergic system leads to neural circuit formation defects. Our study suggests a new therapeutic target for ASD.

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“…The fifth paper, "'Super gene set' casual relationship discovery from functional genomics data", by Zongliang Yue, Michael T. Neylon, Thanh Nguyen, Timothy Ratliff, and Jake J. Chen [5], presents a powerful framework to identify stimulatory and inhibitory regulatory relationships among super gene sets, including pathways, annotated lists, and gene signatures (PAG). They extend their previous work on identifying PAG-to-PAG relationships by further requiring them to be significantly enriched with gene-to-gene coexpression pairs across the two PAGs involved.…”

mentioning

confidence: 99%

Multiscale and Multimodal Analysis for Computational Biology

Gao

Chen

Zaki

2018

IEEE/ACM Trans. Comput. Biol. and Bioinf.

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It brought together international researchers in the interacting disciplines of data mining, medical informatics, and bioinformatics at the World Trade and Convention Centre venue. The goal of this workshop is to encourage Knowledge Discovery and Data mining (KDD) researchers to take on the numerous challenges that Bioinformatics offers. This year, the workshop featured the theme of "Multiscale and multimodal analysis for computational biology".Bioinformatics is the science of managing, mining, and interpreting information from biological data. Various genome projects have contributed to an exponential growth in DNA and protein sequence databases. Rapid advances in high-throughput technologies, such as microarrays, mass spectrometry and new/next-generation sequencing, can monitor quantitatively the presence or activity of thousands of genes, RNAs, proteins, metabolites, and compounds in a given biological state. The ongoing influx of these data, the pressing need to address complex biomedical challenges, and the gap between the two have collectively created exciting opportunities for data mining researchers.While tremendous progress has been made over the years, many of the fundamental problems in bioinformatics, such as protein structure prediction, gene-environment interaction, and regulatory network mapping, have not been convincingly addressed. Besides these, new technologies such as next-generation sequencing are now producing massive amounts of sequence data; managing, mining and compressing these data raise challenging issues. Finally, there is a pressing need to use these data coupled with efficient and effective computational techniques to build models of complex biological processes and disease phenotypes. Data mining plays an essential role in addressing these fundamental problems and in the development of

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“Super Gene Set” Causal Relationship Discovery from Functional Genomics Data

Cited by 4 publications

References 36 publications

Integrative systems and functional analyses reveal a role of dopaminergic signaling in myelin pathogenesis

Integrative systems and functional analyses reveal a role of dopaminergic signaling in myelin pathogenesis

Dopaminergic signaling is linked to neurodevelopmental deficits in autism spectrum disorder (ASD)

Multiscale and Multimodal Analysis for Computational Biology

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