Ontology highlight
ABSTRACT:
PROVIDER: PRJNA682394 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13192432_1.fastq.gz | Fastqsanger.gz | |||
| SRR13192432_2.fastq.gz | Fastqsanger.gz | |||
| SRR13192433_1.fastq.gz | Fastqsanger.gz | |||
| SRR13192433_2.fastq.gz | Fastqsanger.gz | |||
| SRR13192434_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 64 |
Similar Datasets
Project description:This is an SBML version of the folate cycle model model from:
A mathematical model of the folate cycle: new insights into folate homeostasis.
Nijhout HF, Reed MC, Budu P, Ulrich CM
J. Biol. Chem.,2004, 279
(53),55008-16
Reference publication: 15496403
Abstract:
A mathematical model is developed for the folate cycle based on standard biochemical kinetics. We use the model to provide new insights into several different mechanisms of folate homeostasis. The model reproduces the known pool sizes of folate substrates and the fluxes through each of the loops of the folate cycle and has the qualitative behavior observed in a variety of experimental studies. Vitamin B(12) deficiency, modeled as a reduction in the V(max) of the methionine synthase reaction, results in a secondary folate deficiency via the accumulation of folate as 5-methyltetrahydrofolate (the "methyl trap"). One form of homeostasis is revealed by the fact that a 100-fold up-regulation of thymidylate synthase and dihydrofolate reductase (known to occur at the G(1)/S transition) dramatically increases pyrimidine production without affecting the other reactions of the folate cycle. The model also predicts that an almost total inhibition of dihydrofolate reductase is required to significantly inhibit the thymidylate synthase reaction, consistent with experimental and clinical studies on the effects of methotrexate. Sensitivity to variation in enzymatic parameters tends to be local in the cycle and inversely proportional to the number of reactions that interconvert two folate substrates. Another form of homeostasis is a consequence of the nonenzymatic binding of folate substrates to folate enzymes. Without folate binding, the velocities of the reactions decrease approximately linearly as total folate is decreased. In the presence of folate binding and allosteric inhibition, the velocities show a remarkable constancy as total folate is decreased.
A curated
version of this model is available: BIOMD0000000213
.
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 The BioModels.net Team.
For more information see the terms of use
.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL6655501972 | BioModels
Project description:This is an SBML version of the folate cycle model model from:
A mathematical model of the folate cycle: new insights into folate homeostasis.
Nijhout HF, Reed MC, Budu P, Ulrich CM
J. Biol. Chem.,2004, 279
(53),55008-16
pubmedID: 15496403
Abstract:
A mathematical model is developed for the folate cycle based on standard biochemical kinetics. We use the model to provide new insights into several different mechanisms of folate homeostasis. The model reproduces the known pool sizes of folate substrates and the fluxes through each of the loops of the folate cycle and has the qualitative behavior observed in a variety of experimental studies. Vitamin B(12) deficiency, modeled as a reduction in the V(max) of the methionine synthase reaction, results in a secondary folate deficiency via the accumulation of folate as 5-methyltetrahydrofolate (the "methyl trap"). One form of homeostasis is revealed by the fact that a 100-fold up-regulation of thymidylate synthase and dihydrofolate reductase (known to occur at the G(1)/S transition) dramatically increases pyrimidine production without affecting the other reactions of the folate cycle. The model also predicts that an almost total inhibition of dihydrofolate reductase is required to significantly inhibit the thymidylate synthase reaction, consistent with experimental and clinical studies on the effects of methotrexate. Sensitivity to variation in enzymatic parameters tends to be local in the cycle and inversely proportional to the number of reactions that interconvert two folate substrates. Another form of homeostasis is a consequence of the nonenzymatic binding of folate substrates to folate enzymes. Without folate binding, the velocities of the reactions decrease approximately linearly as total folate is decreased. In the presence of folate binding and allosteric inhibition, the velocities show a remarkable constancy as total folate is decreased.
This model was encoded by Michal Galdzicki from a MatLab file send to him by Prof. Michael Reed. There some differences in this model compared to the one described in the article, possible due to typos in the publication:
1) reaction NE (THF + H2CO 5,10-CH2-THF) in the article has H2C=O as a
reactant and is mentioned to display pseudo first order mass action
kinetics, while in the matlab file formic acid, also used in reaction FTS, is included in the rate law for the forward reaction.
2) the reaction MS is modeled after Reed et al. 2004, which is not
explicitly mentioned in the article, although Kd and the parameters
from Reed et al. 2004 are given.
3) in the kinetic law of the SHTM reaction (THF + Ser
5,10-CH2-THF + Gly), there are separate values given for Km,Gly
and Km,5,10-CH2-THF in the article. in the matlab file and the SBML
model Km,Ser and Km,THF are used instead of Km,Gly and Km,5,10-CH2-THF
for the backwards reaction.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2024-09-02 | BIOMD0000000213 | BioModels
Project description:The genomic DNAs of strains 263 of L. infantum and five derived independent resistant mutants to 5-fluorouracil were used in comparative genomic hybridizations to reveal the deletion and/or amplification events occured by drug resistance mechanisms. The human protozoan parasites Leishmania are prototrophic for pyrimidines and de novo pyrimidine biosynthesis is necessary for their growth. Five independent L. infantum mutants were selected for resistance to the pyrimidine analogue 5-fluorouracil (5-FU) in the hope to better understand the metabolism of pyrimidine in Leishmania. Analysis of the 5-FU mutants by comparative genomic hybridization and whole genome sequencing revealed amplification and deletion events as well as point mutations in metabolic genes involved in either the uridine salvage, folate or dTMP biosynthesis pathways. In particular, a dhfr-ts containing amplicon was observed in two mutants and a deletion of part of chromosome 10 was detected in one mutant. Point mutations in uridine phosphorybosyl transferase (UPRT), thymidine kinase (TK) and uridine phosphorylase (UP) were also discovered. Transfection experiments confirmed that these molecular alterations were responsible for the 5-FU resistance phenotype. Transport studies revealed that one resistant mutant was defective for uracil and 5-FU import although the identity of the transporter remains elusive. This study provided further insights in pyrimidine metabolism in Leishmania and confirmed that multiple mutations can co-exist in a cell to lead to resistance. Each independent resistant mutant to 5-fluorouracil was hybridizated with the wild-type L. infantum 263 to 10 microarrays, each with three biological replicates (independent cultures).
2013-12-31 | E-GEOD-45866 | biostudies-arrayexpress
Project description:Pemetrexed is an anticancer agent that exerts its action by disrupting crucial folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed behaves as a multitargeted antifolate by inhibiting thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), which are key folate-dependent enzymes for the de novo biosynthesis of thymidine and purine nucleotides.Pemetrexed is used as a standard therapeutic agent for lung cancer, pleural mesothelioma, peritoneal mesothelioma.In addition to these effective anti-cancer effect, Pemetrexed is not severe side effects of the medicine.
Pemetrexed has been research in colon cancer. Zhang, etc., demonstrated the anti-cancer effect of Pemetrexed in human colon cancer Cells.
Although sometimes made also two or more clinical studies, Pemetrexed was reported 15-17% of the treatment response rate in these two studies.
| 2201098 | ecrin-mdr-crc
Project description:Morrison1989 - Folate Cycle
The model describes the folate cycle
kinetics in breast cancer cells.
This model is described in the article:
Folate cycle kinetics in
human breast cancer cells.
Morrison PF, Allegra CJ.
J. Biol. Chem. 1989 Jun; 264(18):
10552-10566
Abstract:
A mathematical description of polyglutamated folate kinetics
for human breast carcinoma cells (MCF-7) has been formulated
based upon experimental folate, methotrexate (MTX), purine, and
pyrimidine pool sizes as well as reaction rate parameters
obtained from intact MCF-7 cells and their enzyme isolates. The
schema accounts for the interconversion of highly
polyglutamated tetrahydrofolate, 5-methyl-FH4, 5-10-CH2FH4,
dihydrofolate (FH2), 10-formyl-FH4 (FFH4), and 10-formyl-FH2
(FFH2), as well as formation and transport of the MTX
polyglutamates. Inhibition mechanisms have been chosen to
reproduce all observed non-, un-, and pure competition
inhibition patterns. Steady state folate concentrations and
thymidylate and purine synthesis rates in drug-free intact
cells were used to determine normal folate Vmax values. The
resulting average-cell folate model, examined for its ability
to predict folate pool behavior following exposure to 1 microM
MTX over 21 h, agreed well with the experiment, including a
relative preservation of the FFH4 and CH2FH4 pools. The results
depend strongly on thymidylate synthase (TS) reaction
mechanism, especially the assumption that MTX di- and
triglutamates inhibit TS synthesis as greatly in the intact
cell as they do with purified enzyme. The effects of cell cycle
dependence of TS and dihydrofolate reductase activities were
also examined by introducing G- to S-phase activity ratios of
these enzymes into the model. For activity ratios down to at
least 5%, cell population averaged folate pools were only
slightly affected, while CH2FH4 pools in S-phase cells were
reduced to as little as 10% of control values. Significantly,
these folate pool dynamics were indicated to arise from both
direct inhibition by MTX polyglutamates as well as inhibition
by elevated levels of polyglutamated FH2 and FFH2.
Note: two flow BCs were converted into two downstream
concentration BCs, thus removing the GAR and dUMP state
variables. This dropped the number of ODEs from 21 to 19.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000018.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000018 | BioModels
Project description:The human malaria parasite Plasmodium falciparum employs intricate post-transcriptional regulatory mechanisms in different stages of its life cycle. Despite the importance of post-transcriptional regulation, key elements of these processes, namely RNA binding proteins (RBPs), are poorly characterized. In this study, the RNA binding properties of P. falciparum proteins were characterized including two putative members of the Bruno/CELF family of RBPs (PfCELF1 and PfCELF2), dihydrofolate reductase-thymidylate synthase (PfDHFR-TS), and adenosine deaminase (PfAda).The mRNA targets of these P. falciparum proteins were investigated by ribonomics using DNA microarrays.
2014-10-23 | GSE56329 | GEO
Project description:The human malaria parasite Plasmodium falciparum employs intricate post-transcriptional regulatory mechanisms in different stages of its life cycle. Despite the importance of post-transcriptional regulation, key elements of these processes, namely RNA binding proteins (RBPs), are poorly characterized. In this study, the RNA binding properties of P. falciparum proteins were characterized including two putative members of the Bruno/CELF family of RBPs (PfCELF1 and PfCELF2), dihydrofolate reductase-thymidylate synthase (PfDHFR-TS), and adenosine deaminase (PfAda).The mRNA targets of these P. falciparum proteins were investigated by ribonomics using DNA microarrays. Two-condition ribonomic experiment, RBP vs. Mock enrichment of mRNAs. Ribonomic experimental replicates: 4-7 for each RBP, 5 for Mock. One replicate per array.
2014-10-23 | E-GEOD-56329 | biostudies-arrayexpress
Project description:Pemetrexed is a multitargeted antifolate, which primarily inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase in the folate-dependent metabolic process. Nowadays, pemetrexed is used to treat malignant pleural mesothelioma and non-squamous non-small cell lung cancer. Preclinical and clinical studies showed that pemetrexed had cytotoxic activity in many kinds of cancers including colorectal cancer. Erlotinib is a tyrosine-kinase inhibitor of EGFR, which was approved for the treatment of non-small cell lung cancer. Erlotinib also showed activity to colorectal cancer cells. Recently, Zhang et al. demonstrated synergistic cytotoxicity of pemetrexed and gefitinib in preclinical study.
In this multicenter, non randomized, open label phase II study, investigators aimed to evaluate the efficacy and safety of Pemetrexed and Erlotinib combination.
| 2211418 | ecrin-mdr-crc
Project description:To help malaria parasites survive unpredictable host immune responses, it is known that genes for surface proteins express stochastically in Plasmodium falciparum. Here, we demonstrate that gene expression for intracellular metabolic functions may be preordained and insensitive to specific metabolic perturbations. In a tightly-controlled, large microarray study involving over 100 hybridizations to isogenic drug-sensitive and drug-resistant parasites, the lethal antifolate WR99210 failed to over-produce RNA for the biochemically and genetically proven target dihydrofolate reductase-thymidylate synthase (DHFR-TS). Beyond the target, this transcriptional obstinacy carried over to the rest of the parasite genome, including genes for target pathways of folate and pyrimidine metabolism. Even 12 hours after commitment to death, the transcriptome remained faithful to evolutionarily entrained paths. A system-wide transcriptional disregard for metabolic perturbations in malaria parasites may contribute to selective vulnerabilities of the parasite to lethal antimetabolites. While large protective metabolic responses were not detected, DNA microarrays helped capture small, but reproducible drug-dependent perturbations within hours of drug exposure. In addition, in Plasmodium cells that had adapted to long-term drug exposure, DNA microarrays revealed new, large genome-wide transcriptional adjustments in the hard-wired transcriptional program itself. Keywords: Plasmodium falciparum treated with pyrimethamine RNA from pyrimethamine-treated parasite vs RNA from untreated control, Pyr-sensitive TM4/8.2 strain, pyrimethamine concentration at IC50 and treated for 0 h and 24 h, microarray data were obtained from at least four hybridizations using RNA from at lease two independent parasite cultures
2010-05-16 | E-GEOD-9853 | biostudies-arrayexpress
Project description:The genomic DNAs of strains 263 of L. infantum and five derived independent resistant mutants to 5-fluorouracil were used in comparative genomic hybridizations to reveal the deletion and/or amplification events occured by drug resistance mechanisms. The human protozoan parasites Leishmania are prototrophic for pyrimidines and de novo pyrimidine biosynthesis is necessary for their growth. Five independent L. infantum mutants were selected for resistance to the pyrimidine analogue 5-fluorouracil (5-FU) in the hope to better understand the metabolism of pyrimidine in Leishmania. Analysis of the 5-FU mutants by comparative genomic hybridization and whole genome sequencing revealed amplification and deletion events as well as point mutations in metabolic genes involved in either the uridine salvage, folate or dTMP biosynthesis pathways. In particular, a dhfr-ts containing amplicon was observed in two mutants and a deletion of part of chromosome 10 was detected in one mutant. Point mutations in uridine phosphorybosyl transferase (UPRT), thymidine kinase (TK) and uridine phosphorylase (UP) were also discovered. Transfection experiments confirmed that these molecular alterations were responsible for the 5-FU resistance phenotype. Transport studies revealed that one resistant mutant was defective for uracil and 5-FU import although the identity of the transporter remains elusive. This study provided further insights in pyrimidine metabolism in Leishmania and confirmed that multiple mutations can co-exist in a cell to lead to resistance.
2013-12-31 | GSE45866 | GEO