Background: Prediction of biochemical (metabolic) pathways has a wide range of applications, including the optimization of drug candidates, and the elucidation of toxicity mechanisms. Recently, several methods have been developed for pathway prediction to derive a goal compound from a start compound. However, these methods require high computational costs, and cannot perform comprehensive prediction of novel metabolic pathways. Our aim of this study is to develop a de novo prediction method for reconstructions of metabolic pathways and predictions of unknown biosynthetic pathways in the sense that it does not require any initial network such as KEGG metabolic network to be explored.
Results: We formulated pathway prediction between a start compound and a goal compound as the shortest path search problem in terms of the number of enzyme reactions applied. We propose an efficient search method based on A* algorithm and heuristic techniques utilizing Linear Programming (LP) solution for estimation of the distance to the goal. First, a chemical compound is represented by a feature vector which counts frequencies of substructure occurrences in the structural formula. Second, an enzyme reaction is represented as an operator vector by detecting the structural changes to compounds before and after the reaction. By defining compound vectors as nodes and operator vectors as edges, prediction of the reaction pathway is reduced to the shortest path search problem in the vector space. In experiments on the DDT degradation pathway, we verify that the shortest paths predicted by our method are biologically correct pathways registered in the KEGG database. The results also demonstrate that the LP heuristics can achieve significant reduction in computation time. Furthermore, we apply our method to a secondary metabolite pathway of plant origin, and successfully find a novel biochemical pathway which cannot be predicted by the existing method. For the reconstruction of a known biochemical pathway, our method is over 40 times as fast as the existing method.
Conclusions: Our method enables fast and accurate de novo pathway predictions and novel pathway detection.
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http://dx.doi.org/10.1186/1471-2105-13-S17-S8 | DOI Listing |
Cureus
December 2024
Department of Cardiology, Japanese Red Cross Maebashi Hospital, Maebashi, JPN.
When encountering severe hypoxemia that does not respond to oxygen supplementation, it is essential to consider underlying right-to-left shunting. Among various diagnostic approaches, the microbubble test via transthoracic echocardiography (TTE) is a simple, noninvasive method for detecting pulmonary arteriovenous shunts, particularly in hepatopulmonary syndrome (HPS). Although microbubbles are usually administered peripherally, using a Swan-Ganz (SG) catheter to inject microbubbles directly into the pulmonary artery may provide even more definitive diagnostic information.
View Article and Find Full Text PDFIntroduction: Idiopathic Intracranial Hypertension (IIH) presents an increasing health burden with changing demographic patterns. We studied nationwide trends in IIH epidemiology, treatment patterns, and associated outcomes using a large-scale database analysis within the United States (US).
Methods: We performed a retrospective analysis using the TriNetX US Collaborative Network database (1990-2024).
Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, exhibiting clinical and genomic heterogeneity. Of the four major subgroups, Group 3 tumors (MYC-MB), display high levels of MYC and metastasis rates. Despite treatment with surgery, radiation, and chemotherapy, patients with Group 3 MB are more likely to develop aggressive recurrent tumors with poor survival.
View Article and Find Full Text PDFJ Pineal Res
November 2024
School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China.
The dried root of Peucedanum praeruptorum is often used medicinally and has high pyran- and furanocoumarin content. Although exogenous melatonin (MT) impacts the regulation of plant growth, stress responses, secondary metabolism, etc., it remains unclear whether MT regulates the vegetative growth and development of P.
View Article and Find Full Text PDFFuture Microbiol
December 2024
Department of Pharmacy, The Third Affiliated Hospital of Soochow University/The First People's Hospital of Changzhou, Changzhou, Jiangsu, China.
Aims: A notable scarcity of research has focused on examining alterations in gut microbiota and its metabolites within tacrolimus (TAC)-induced diabetes models.
Methods: Tacrolimus-induced changes in glucose and lipid metabolism indices were analyzed through different routes of administration. The potential role of gut microbiota and its metabolites in TAC-induced diabetes was investigated using 16S rRNA sequencing and non-targeted metabolomics.
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