Mislocalization-related disease gene discovery using gene expression based computational protein localization prediction

Liu, Zhonghao; Hu, Jianjun

doi:10.1016/j.ymeth.2015.09.022

Cited by 17 publications

(11 citation statements)

References 67 publications

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“…Because abnormal localization of proteins participates in the pathogenesis of many human diseases ( Hung and Link, 2011 ; Agostinho et al , 2015 ; Liu and Hu, 2016 ), we also studied localization differences of pyrin-fl and pyrin-d2 exploring the localization of recombinant constructs via confocal microscopy. Our results also confirmed that pyrin full-length form was localized in cytoplasm and exon 2 spliced form in nucleus of HL-60 cell-line.…”

Section: Introductionmentioning

confidence: 99%

Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models

et al. 2017

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The function of gene body DNA methylation in alternative splicing, and its relation to disease pathogenesis is not fully elucidated. The gene for familial Mediterranean fever (MEFV) encodes the pyrin protein and contains a 998 bp CpG island, covering the second exon, which is differentially methylated in FMF patients compared to healthy controls. Our further observation of increased exon 2-spliced MEFV transcript in leukocytes of FMF patients provoked us to test the role of exon methylation in alternative splicing using inflammatory cell culture models. First, in vitro exon methylation triggered an increased level of exon 2 exclusion using a splicing cassette in a promyelocytic leukemia cell line (HL-60). HL-60 cells subjected to methylating and demethylating agents, as well as cells differentiated to neutrophil-like cells, exhibited different levels of spliced/unspliced transcripts. We observed increased levels of spliced transcripts in neutrophil-like (p = 0.0005), activated (p = 0.0034) and methylated cells (p < 0.0001), whereas decreased levels in demethylated cells (p = 0.0126) compared to control untreated HL-60 cells. We also showed that the protein isoform of pyrin lacking the exon 2 has an adverse subcellular localization in neutrophil-like cells. Therefore, it remains in the cytoplasm rather than the nucleus. This may point to an epigenetic involvement in an important inflammatory gene.

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Section: Introductionmentioning

confidence: 99%

Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models

et al. 2017

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“…It should be noted that our method is designed to find out the alteration of protein subcellular locations, rather than the exact subcellular locations in non-disease state. Therefore, we choose to compare our method to Liu and Hu's method (Liu and Hu, 2016). Since we applied virtual locative protein concept in our work, while Liu and Hu employed the top-k accuracy performance measure, it is difficult to perform an exact apple-to-apple orange-toorange comparison.…”

Section: Results and Discussion Prediction Performance Analysis In Thmentioning

confidence: 99%

“…Most of these works rely on machine learning algorithms (Chou, 2011). Unfortunately, almost all existing studies, which focus on predicting protein subcellular locations, only predict subcellular locations for a given protein in only one condition (Liu and Hu, 2016). This is because almost all existing studies of this kind utilize only the static information as the input data.…”

Section: Introductionmentioning

confidence: 99%

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DPPN-SVM: Computational Identification of Mis-Localized Proteins in Cancers by Integrating Differential Gene Expressions With Dynamic Protein-Protein Interaction Networks

Shen

et al. 2020

Front. Genet.

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Eukaryotic cells contain numerous components, which are known as subcellular compartments or subcellular organelles. Proteins must be sorted to proper subcellular compartments to carry out their molecular functions. Mis-localized proteins are related to various cancers. Identifying mis-localized proteins is important in understanding the pathology of cancers and in developing therapies. However, experimental methods, which are used to determine protein subcellular locations, are always costly and timeconsuming. We tried to identify cancer-related mis-localized proteins in three different cancers using computational approaches. By integrating gene expression profiles and dynamic protein-protein interaction networks, we established DPPN-SVM (Dynamic Protein-Protein Network with Support Vector Machine), a predictive model using the SVM classifier with diffusion kernels. With this predictive model, we identified a number of mis-localized proteins. Since we introduced the dynamic protein-protein network, which has never been considered in existing works, our model is capable of identifying more mis-localized proteins than existing studies. As far as we know, this is the first study to incorporate dynamic protein-protein interaction network in identifying mis-localized proteins in cancers.

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“…Subcellular localization determines the access of proteins to interacting partners and the post-translational modification machinery, which enables the integration of proteins into functional biological network [ 42 ]. It has also been demonstrated that the abnormalities of subcellular locations of protein are potentially involved in the pathogenesis of many human diseases [ 42 , 43 , 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Histological Analysis, Bioinformatics Profile, and Expression of Methylenetetrahydrofolate Reductase (MTHFR) in Bovine Testes

Afedo

Cui

et al. 2020

Animals

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Methylenetetrahydrofolate reductase (MTHFR), an enzyme expressed in mammalian testes, exerts a direct effect on spermatogenesis; however, its protein characteristics in bovine testes remain unknown. Here, we analysed bovine testicular structure, MTHFR bioinformatics profile, mRNA, and protein expression characteristics in yellow-cattle (y-c) and yak testis using histological procedures, bioinformatics analysis, qRT-PCR, and western blot. Testes from 13 bovines, ≤2 years juvenile (y-c, n = 3; yak, n = 3) and ≥3 years adult (y-c, n = 3; yak, n = 4) were collected and analysed. Anatomical characteristics of testis in y-c and yak were similar except the weight or size for which that of y-c was significantly higher or greater than yak. In y-c, an open reading frame (ORF) for 2600 nucleotides sequence, encoding 655 amino acids showed high homology with zebu cattle (99.51%) and wild yak (98.68%). Secondary and 3D protein structures were similar to that of humans with differences in the number of nucleotides, amino acids, and some physico-chemical characteristics. MTHFR mRNA expression in y-c and yak were significantly higher in adult testes compared with juvenile ones. However, its protein expression was higher, but not statistically significant, in adult y-c and yak compared to the juvenile ones. The highlights and inferences of these and other findings are discussed.

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Mislocalization-related disease gene discovery using gene expression based computational protein localization prediction

Cited by 17 publications

References 67 publications

Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models

Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models

DPPN-SVM: Computational Identification of Mis-Localized Proteins in Cancers by Integrating Differential Gene Expressions With Dynamic Protein-Protein Interaction Networks

Histological Analysis, Bioinformatics Profile, and Expression of Methylenetetrahydrofolate Reductase (MTHFR) in Bovine Testes

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