scholarly journals Exploring the Metabolic Heterogeneity of Cancers: A Benchmark Study of Context-Specific Models

2021 ◽  
Vol 11 (6) ◽  
pp. 496
Author(s):  
Mahdi Jalili ◽  
Martin Scharm ◽  
Olaf Wolkenhauer ◽  
Mehdi Damaghi ◽  
Ali Salehzadeh-Yazdi
Keyword(s):  
Learning Algorithm ◽  
Metabolic Model ◽  
Relevant Information ◽  
Quality Data ◽  
Metabolic Pattern ◽  
Metabolic Fingerprint ◽  
Balance Analysis ◽  
Cancer Phenotype ◽  
Metabolic Heterogeneity ◽  
Context Specific

Metabolic heterogeneity is a hallmark of cancer and can distinguish a normal phenotype from a cancer phenotype. In the systems biology domain, context-specific models facilitate extracting physiologically relevant information from high-quality data. Here, to utilize the heterogeneity of metabolic patterns to discover biomarkers of all cancers, we benchmarked thousands of context-specific models using well-established algorithms for the integration of omics data into the generic human metabolic model Recon3D. By analyzing the active reactions capable of carrying flux and their magnitude through flux balance analysis, we proved that the metabolic pattern of each cancer is unique and could act as a cancer metabolic fingerprint. Subsequently, we searched for proper feature selection methods to cluster the flux states characterizing each cancer. We employed PCA-based dimensionality reduction and a random forest learning algorithm to reveal reactions containing the most relevant information in order to effectively identify the most influential fluxes. Conclusively, we discovered different pathways that are probably the main sources for metabolic heterogeneity in cancers. We designed the GEMbench website to interactively present the data, methods, and analysis results.

scholarly journals Flux-dependent graphs for metabolic networks

2018 ◽  
Author(s):  
Mariano Beguerisse-Díaz ◽  
Gabriel Bosque ◽  
Diego Oyarzún ◽  
Jesús Picóo ◽  
Mauricio Barahona
Keyword(s):  
Metabolic Networks ◽  
Metabolic Model ◽  
Central Carbon Metabolism ◽  
System Level ◽  
Metabolic Fluxes ◽  
Genetic Perturbations ◽  
Balance Analysis ◽  
Frame Work ◽  
Context Specific ◽  
Specific Reactions

Cells adapt their metabolic fluxes in response to changes in the environment. We present a frame-work for the systematic construction of flux-based graphs derived from organism-wide metabolic networks. Our graphs encode the directionality of metabolic fluxes via edges that represent the flow of metabolites from source to target reactions. The methodology can be applied in the absence of a specific biological context by modelling fluxes probabilistically, or can be tailored to different environ-mental conditions by incorporating flux distributions computed through constraint-based approaches such as Flux Balance Analysis. We illustrate our approach on the central carbon metabolism ofEscherichia coliand on a metabolic model of human hepatocytes. The flux-dependent graphs under various environmental conditions and genetic perturbations exhibit systemic changes in their topo-logical and community structure, which capture the re-routing of metabolic fluxes and the varying importance of specific reactions and pathways. By integrating constraint-based models and tools from network science, our framework allows the study of context-specific metabolic responses at a system level beyond standard pathway descriptions.

scholarly journals Drought Stress Responses in Context-Specific Genome-Scale Metabolic Models of Arabidopsis thaliana

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 159
Author(s):  
Ratklao Siriwach ◽  
Fumio Matsuda ◽  
Kentaro Yano ◽  
Masami Yokota Hirai
Keyword(s):  
Arabidopsis Thaliana ◽  
Drought Stress ◽  
Stress Responses ◽  
In Silico ◽  
Metabolic Model ◽  
Metabolic Reaction ◽  
A Genome ◽  
Balance Analysis ◽  
Context Specific ◽  
Genome Scale

Drought perturbs metabolism in plants and limits their growth. Because drought stress on crops affects their yields, understanding the complex adaptation mechanisms evolved by plants against drought will facilitate the development of drought-tolerant crops for agricultural use. In this study, we examined the metabolic pathways of Arabidopsis thaliana which respond to drought stress by omics-based in silico analyses. We proposed an analysis pipeline to understand metabolism under specific conditions based on a genome-scale metabolic model (GEM). Context-specific GEMs under drought and well-watered control conditions were reconstructed using transcriptome data and examined using metabolome data. The metabolic fluxes throughout the metabolic network were estimated by flux balance analysis using the context-specific GEMs. We used in silico methods to identify an important reaction contributing to biomass production and clarified metabolic reaction responses under drought stress by comparative analysis between drought and control conditions. This proposed pipeline can be applied in other studies to understand metabolic changes under specific conditions using Arabidopsis GEM or other available plant GEMs.

scholarly journals DEXOM: Diversity-based enumeration of optimal context-specific metabolic networks

2020 ◽  
Author(s):  
Pablo Rodríguez-Mier ◽  
Nathalie Poupin ◽  
Carlo de Blasio ◽  
Laurent Le Cam ◽  
Fabien Jourdan
Keyword(s):  
Metabolic Network ◽  
Metabolic Networks ◽  
Relevant Information ◽  
Experimental Information ◽  
Correct Identification ◽  
Good Representation ◽  
Metabolic State ◽  
Whole Space ◽  
Context Specific ◽  
Optimal Networks

AbstractThe correct identification of metabolic activity in tissues or cells under different environmental or genetic conditions can be extremely elusive due to mechanisms such as post-transcriptional modification of enzymes or different rates in protein degradation, making difficult to perform predictions on the basis of gene expression alone. Context-specific metabolic network reconstruction can overcome these limitations by leveraging the integration of multi-omics data into genome-scale metabolic networks (GSMN). Using the experimental information, context-specific models are reconstructed by extracting from the GSMN the sub-network most consistent with the data, subject to biochemical constraints. One advantage is that these context-specific models have more predictive power since they are tailored to the specific organism and condition, containing only the reactions predicted to be active in such context. A major limitation of this approach is that the available information does not generally allow for an unambiguous characterization of the corresponding optimal metabolic sub-network, i.e., there are usually many different sub-network that optimally fit the experimental data. This set of optimal networks represent alternative explanations of the possible metabolic state. Ignoring the set of possible solutions reduces the ability to obtain relevant information about the metabolism and may bias the interpretation of the true metabolic state. In this work, we formalize the problem of enumeration of optimal metabolic networks, we implement a set of techniques that can be used to enumerate optimal networks, and we introduce DEXOM, a novel strategy for diversity-based extraction of optimal metabolic networks. Instead of enumerating the whole space of optimal metabolic networks, which can be computationally intractable, DEXOM samples solutions from the set of optimal metabolic sub-networks maximizing diversity in order to obtain a good representation of the possible metabolic state. We evaluate the solution diversity of the different techniques using simulated and real datasets, and we show how this method can be used to improve in-silico gene essentiality predictions in Saccharomyces Cerevisiae using diversity-based metabolic network ensembles. Both the code and the data used for this research are publicly available on GitHub1.

A Bird’s Eye View of 100 years of research on Hypertension: Machine Learning Classifications of Topics (Preprint)

2021 ◽  
Author(s):  
Mustapha Abba ◽  
Chidozie Nduka ◽  
Seun Anjorin ◽  
Shukri Mohamed ◽  
Emmanuel Agogo ◽  
...  
Keyword(s):  
Machine Learning ◽  
Latent Dirichlet Allocation ◽  
Learning Algorithm ◽  
Temporal Trends ◽  
Relevant Information ◽  
Research Articles ◽  
Major Cardiovascular Events ◽  
And Shifts ◽  
Negative Sentiment ◽  
Over Time

BACKGROUND Due to scientific and technical advancements in the field, published hypertension research has developed during the last decade. Given the huge amount of scientific material published in this field, identifying the relevant information is difficult. We employed topic modelling, which is a strong approach for extracting useful information from enormous amounts of unstructured text. OBJECTIVE To utilize a machine learning algorithm to uncover hidden topics and subtopics from 100 years of peer-reviewed hypertension publications and identify temporal trends. METHODS The titles and abstracts of hypertension papers indexed in PubMed were examined. We used the Latent Dirichlet Allocation (LDA) model to select 20 primary subjects and then ran a trend analysis to see how popular they were over time. RESULTS We gathered 581,750 hypertension-related research articles from 1900 to 2018 and divided them into 20 categories. Preclinical, risk factors, complications, and therapy studies were the categories used to categorise the publications. We discovered themes that were becoming increasingly ‘hot,' becoming less ‘cold,' and being published seldom. Risk variables and major cardiovascular events subjects displayed very dynamic patterns over time (how? – briefly detail here). The majority of the articles (71.2%) had a negative valency, followed by positive (20.6%) and neutral valencies (8.2 percent). Between 1980 and 2000, negative sentiment articles fell somewhat, while positive and neutral sentiment articles climbed significantly. CONCLUSIONS This unique machine learning methodology provided fascinating insights on current hypertension research trends. This method allows researchers to discover study subjects and shifts in study focus, and in the end, it captures the broader picture of the primary concepts in current hypertension research articles. CLINICALTRIAL Not applicable

A portable method for acquiring information extraction patterns without annotated corpora

2003 ◽  
Vol 9 (2) ◽  
pp. 151-179 ◽  
Author(s):  
NEUS CATALÀ ◽  
NÚRIA CASTELL ◽  
MARIO MARTÍN
Keyword(s):  
Information Extraction ◽  
Learning Algorithm ◽  
Relevant Information ◽  
General Purpose ◽  
Human Intervention ◽  
Lexical Knowledge ◽  
Distinctive Features ◽  
Domain Specific ◽  
Building Information ◽  
Automatic Acquisition

The main issue when building Information Extraction (IE) systems is how to obtain the knowledge needed to identify relevant information in a document. Most approaches require expert human intervention in many steps of the acquisition process. In this paper we describe ESSENCE, a new method for acquiring IE patterns that significantly reduces the need for human intervention. The method is based on ELA, a specifically designed learning algorithm for acquiring IE patterns without tagged examples. The distinctive features of ESSENCE and ELA are that (1) they permit the automatic acquisition of IE patterns from unrestricted and untagged text representative of the domain, due to (2) their ability to identify regularities around semantically relevant concept-words for the IE task by (3) using non-domain-specific lexical knowledge tools such as WordNet, and (4) restricting the human intervention to defining the task, and validating and typifying the set of IE patterns obtained. Since ESSENCE does not require a corpus annotated with the type of information to be extracted and it uses a general purpose ontology and widely applied syntactic tools, it reduces the expert effort required to build an IE system and therefore also reduces the effort of porting the method to any domain. The results of the application of ESSENCE to the acquisition of IE patterns in an MUC-like task are shown.

scholarly journals Biochemical Characteristics and a Genome-Scale Metabolic Model of an Indian Euryhaline Cyanobacterium with High Polyglucan Content

Metabolites ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 177 ◽  
Author(s):  
Ahmad Ahmad ◽  
Ruchi Pathania ◽  
Shireesh Srivastava
Keyword(s):  
Biomass Accumulation ◽  
Metabolic Model ◽  
Metabolic Characteristics ◽  
Protein Levels ◽  
A Genome ◽  
Lower Protein ◽  
Balance Analysis ◽  
Synechococcus Sp ◽  
The Difference ◽  
Genome Scale

Marine cyanobacteria are promising microbes to capture and convert atmospheric CO2 and light into biomass and valuable industrial bio-products. Yet, reports on metabolic characteristics of non-model cyanobacteria are scarce. In this report, we show that an Indian euryhaline Synechococcus sp. BDU 130192 has biomass accumulation comparable to a model marine cyanobacterium and contains approximately double the amount of total carbohydrates, but significantly lower protein levels compared to Synechococcus sp. PCC 7002 cells. Based on its annotated chromosomal genome sequence, we present a genome scale metabolic model (GSMM) of this cyanobacterium, which we have named as iSyn706. The model includes 706 genes, 908 reactions, and 900 metabolites. The difference in the flux balance analysis (FBA) predicted flux distributions between Synechococcus sp. PCC 7002 and Synechococcus sp. BDU130192 strains mimicked the differences in their biomass compositions. Model-predicted oxygen evolution rate for Synechococcus sp. BDU130192 was found to be close to the experimentally-measured value. The model was analyzed to determine the potential of the strain for the production of various industrially-useful products without affecting growth significantly. This model will be helpful to researchers interested in understanding the metabolism as well as to design metabolic engineering strategies for the production of industrially-relevant compounds.

A NEURAL NETWORK MODEL TO INDEX MEDICAL IMAGES

1999 ◽  
Vol 07 (01) ◽  
pp. 45-51
Author(s):  
JEAN-CHARLES CRÉPUT ◽  
ARMAND CARON
Keyword(s):  
Neural Network ◽  
Learning Algorithm ◽  
Parallel Implementation ◽  
Relevant Information ◽  
Complex Data ◽  
Robust Algorithms ◽  
Network Information ◽  
Binary Relevance ◽  
Two Phases ◽  
Learning Data

With the development of computer capabilities, memories and network abilities, we need more efficient and robust algorithms to manage databases and to store and retrieve the relevant information for the user. The aim of this work is to automate the construction of a neural network Information Retrieval System (IRS) adapted to a medical image database. The user builds queries and the system must retrieve the relevant documents or images. Queries are groups of keywords or items associated with relevant images. In our approach, the set of queries and the binary relevance judgments on the documents constitute complex learning data associations. There are two phases in the automatic construction of the IRS. The indexing phase builds the learning data base and then a specific learning algorithm builds the neural network. For the system to be able to immediately learn these complex data, we have developed a new specific algorithm. It allows a perfect learning of a binary logical table in a stepwise fashion without forgetting the previously learnt logical combinations. Furthermore, this algorithm works very quickly and leads to a parallel implementation for large databases.

scholarly journals A non-spatial account of place and grid cells based on clustering models of concept learning

2018 ◽  
Author(s):  
Robert M. Mok ◽  
Bradley C. Love
Keyword(s):  
Medial Temporal Lobe ◽  
Conceptual Knowledge ◽  
Learning Algorithm ◽  
Grid Cell ◽  
Relevant Information ◽  
Neural Circuitry ◽  
General Purpose ◽  
Clustering Model ◽  
Higher Dimensional ◽  
Processing Steps

ABSTRACTOne view is that conceptual knowledge is organized using the circuitry in the medial temporal lobe (MTL) that supports spatial processing and navigation. In contrast, we find that a domain-general learning algorithm explains key findings in both spatial and conceptual domains. When the clustering model is applied to spatial navigation tasks, so called place and grid cell-like representations emerge because of the relatively uniform distribution of possible inputs in these tasks. The same mechanism applied to conceptual tasks, where the overall space can be higher-dimensional and sampling sparser, leads to representations more aligned with human conceptual knowledge. Although the types of memory supported by the MTL are superficially dissimilar, the information processing steps appear shared. Our account suggests that the MTL uses a general-purpose algorithm to learn and organize context-relevant information in a useful format, rather than relying on navigation-specific neural circuitry.

scholarly journals UniAssist- Implementation of Machine Learning Based Higher Education University Recommendation System

2020 ◽  
pp. 262-266
Keyword(s):  
Higher Education ◽  
Machine Learning ◽  
Work Experience ◽  
Recommendation System ◽  
Learning Algorithm ◽  
Relevant Information ◽  
Mobile App ◽  
Admission Process ◽  
Software Application ◽  
Tuition Fee

UniAssist project is implemented to help students who have completed their Bachelorette degree and are looking forward to study abroad to pursue their higher education such as Masters. Machine Learning would help identify appropriate Universities for such students and suggest them accordingly. UniAssist would help such individuals by recommending those Universities according to their preference of course, country and considering their grades, work experience and qualifications. There is a need for students hoping to pursue higher education outside India to get to know about proper universities. Data collected is then converted into relevant information that is currently not easily available such as courses offered by their dream universities, the avg. tuition fee and even the avg. expense of living near the chosen university on single mobile app based software platform. This is the first phase of the admission process for every student. The machine-learning algorithm used is Collaborative filtering memory-based approach using KNN calculated using cosine similarity. A mobile-based software application is implemented in order to help and guide students for their higher education.

scholarly journals Inhibiting the reproduction of SARS-CoV-2 through perturbations in human lung cell metabolic network

2020 ◽  
Vol 4 (1) ◽  
pp. e202000869
Author(s):  
Hadrien Delattre ◽  
Kalesh Sasidharan ◽  
Orkun S Soyer
Keyword(s):  
Metabolic Flux ◽  
Human Lung ◽  
Structural Information ◽  
Experimental Testing ◽  
Metabolic Model ◽  
Emerging Viruses ◽  
Nucleotide Biosynthesis ◽  
Human Lung Cells ◽  
Balance Analysis ◽  
Biomass Function

Viruses rely on their host for reproduction. Here, we made use of genomic and structural information to create a biomass function capturing the amino and nucleic acid requirements of SARS-CoV-2. Incorporating this biomass function into a stoichiometric metabolic model of the human lung cell and applying metabolic flux balance analysis, we identified host-based metabolic perturbations inhibiting SARS-CoV-2 reproduction. Our results highlight reactions in the central metabolism, as well as amino acid and nucleotide biosynthesis pathways. By incorporating host cellular maintenance into the model based on available protein expression data from human lung cells, we find that only few of these metabolic perturbations are able to selectively inhibit virus reproduction. Some of the catalysing enzymes of such reactions have demonstrated interactions with existing drugs, which can be used for experimental testing of the presented predictions using gene knockouts and RNA interference techniques. In summary, the developed computational approach offers a platform for rapid, experimentally testable generation of drug predictions against existing and emerging viruses based on their biomass requirements.

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