scholarly journals Inferring the metabolism of human orphan metabolites from their metabolic network context affirms human gluconokinase activity

2012 ◽  
Vol 449 (2) ◽  
pp. 427-435 ◽  
Author(s):  
Óttar Rolfsson ◽  
Giuseppe Paglia ◽  
Manuela Magnusdóttir ◽  
Bernhard Ø. Palsson ◽  
Ines Thiele

Metabolic network reconstructions define metabolic information within a target organism and can therefore be used to address incomplete metabolic information. In the present study we used a computational approach to identify human metabolites whose metabolism is incomplete on the basis of their detection in humans but exclusion from the human metabolic network reconstruction RECON 1. Candidate solutions, composed of metabolic reactions capable of explaining the metabolism of these compounds, were then identified computationally from a global biochemical reaction database. Solutions were characterized with respect to how metabolites were incorporated into RECON 1 and their biological relevance. Through detailed case studies we show that biologically plausible non-intuitive hypotheses regarding the metabolism of these compounds can be proposed in a semi-automated manner, in an approach that is similar to de novo network reconstruction. We subsequently experimentally validated one of the proposed hypotheses and report that C9orf103, previously identified as a candidate tumour suppressor gene, encodes a functional human gluconokinase. The results of the present study demonstrate how semi-automatic gap filling can be used to refine and extend metabolic reconstructions, thereby increasing their biological scope. Furthermore, we illustrate how incomplete human metabolic knowledge can be coupled with gene annotation in order to prioritize and confirm gene functions.

2016 ◽  
Vol 85 (2) ◽  
pp. 289-304 ◽  
Author(s):  
Huili Yuan ◽  
C.Y. Maurice Cheung ◽  
Mark G. Poolman ◽  
Peter A. J. Hilbers ◽  
Natal A. W. Riel

2018 ◽  
Vol 14 (10) ◽  
pp. e1006541 ◽  
Author(s):  
Hao Wang ◽  
Simonas Marcišauskas ◽  
Benjamín J. Sánchez ◽  
Iván Domenzain ◽  
Daniel Hermansson ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Yang Cao ◽  
Xiaofei Zheng ◽  
Fei Li ◽  
Xiaochen Bo

The human microbiome plays important roles in human health and disease. Previous microbiome studies focused mainly on single pure species function and overlooked the interactions in the complex communities on system-level. A metagenomic approach introduced recently integrates metagenomic data with community-level metabolic network modeling, but no comprehensive tool was available for such kind of approaches. To facilitate these kinds of studies, we developed an R package,mmnet, to implement community-level metabolic network reconstruction. The package also implements a set of functions for automatic analysis pipeline construction including functional annotation of metagenomic reads, abundance estimation of enzymatic genes, community-level metabolic network reconstruction, and integrated network analysis. The result can be represented in an intuitive way and sent to Cytoscape for further exploration. The package has substantial potentials in metagenomic studies that focus on identifying system-level variations of human microbiome associated with disease.


2019 ◽  
Vol 105 ◽  
pp. 64-71 ◽  
Author(s):  
Kristopher D. Rawls ◽  
Bonnie V. Dougherty ◽  
Edik M. Blais ◽  
Ethan Stancliffe ◽  
Glynis L. Kolling ◽  
...  

2007 ◽  
Vol 3 (1) ◽  
pp. 135 ◽  
Author(s):  
Hongwu Ma ◽  
Anatoly Sorokin ◽  
Alexander Mazein ◽  
Alex Selkov ◽  
Evgeni Selkov ◽  
...  

2020 ◽  
pp. jmedgenet-2020-107087
Author(s):  
Zerin Hyder ◽  
Adele Fairclough ◽  
Mike Groom ◽  
Joan Getty ◽  
Elizabeth Alexander ◽  
...  

BackgroundNephroblastomatosis is a recognised precursor for the development of Wilms tumour (WT), the most common childhood renal tumour. While the majority of WT is sporadic in origin, germline intragenic mutations of predisposition genes such as WT1, REST and TRIM28 have been described in apparently isolated (non-familial) WT.Despite constitutional CNVs being a well-studied cause of developmental disorders, their role in cancer predisposition is less well defined, so that the interpretation of cancer risks associated with specific CNVs can be complex.ObjectiveTo highlight the role of a constitutional deletion CNV (delCNV) encompassing the REST tumour suppressor gene in diffuse hyperplastic perilobar nephroblastomatosis (HPLN).Methods/resultsArray comparative genomic hybridisation in an infant presenting with apparently sporadic diffuse HPLN revealed a de novo germline CNV, arr[GRCh37] 4q12(57,385,330–57,947,405)x1. The REST tumour suppressor gene is located at GRCh37 chr4:57,774,042–57,802,010.ConclusionThis delCNV encompassing REST is associated with nephroblastomatosis. Deletion studies should be included in the molecular work-up of inherited predisposition to WT/nephroblastomatosis. Detection of delCNVs involving known cancer predisposition genes can yield insights into the relationship between underlying genomic architecture and associated tumour risk.


2008 ◽  
Vol 26 (10) ◽  
pp. 1155-1160 ◽  
Author(s):  
Markus J Herrgård ◽  
Neil Swainston ◽  
Paul Dobson ◽  
Warwick B Dunn ◽  
K Yalçin Arga ◽  
...  

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