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377 Publications visible to you, out of a total of 377
Panel of three novel serum markers predicts liver stiffness and fibrosis stages in patients with chronic liver disease.

Abstract (Expand)

Latest data suggest that placental growth factor (PLGF), growth differentiation factor-15 (GDF-15) and hepatic growth factor (HGF) are involved in hepatic fibrogenesis. Diagnostic performance of these … markers for non-invasive liver fibrosis prediction was evaluated based on liver histology and stiffness. In total 834 patients were recruited. Receiver-operating-characteristics were used to define cut-offs for markers correlating to fibrosis stages. Odds-ratios were calculated for the presence/absence of fibrosis/cirrhosis and confirmed in the sub-group of patients phenotyped by elastography only. Logistic and uni- and multivariate regression analyses were used to test for association of markers with liver fibrosis stages and for independent prediction of liver histology and stiffness. Marker concentrations correlated significantly (P<0.001) with histology and stiffness. Cut-offs for liver fibrosis (>/=F2) were PLGF = 20.20 pg/ml, GDF15 = 1582.76 pg/ml and HGF = 2598.00 pg/ml. Logistic regression confirmed an increase of ORs from 3.6 over 33.0 to 108.4 with incremental (1-3) markers positive for increased liver stiffness (>/=12.8kPa; all P<0.05). Subgroup analysis revealed associations with advanced fibrosis for HCV (three markers positive: OR = 59.9, CI 23.4-153.4, P<0.001) and non-HCV patients (three markers positive: OR = 144, CI 59-3383, P<0.001). Overall, serum markers identified additional 50% of patients at risk for advanced fibrosis presenting with low elastography results. In conclusion, this novel combination of markers reflects the presence of significant liver fibrosis detected by elastography and histology and may also identify patients at risk presenting with low elastography values.

Authors: M. Krawczyk, S. Zimmermann, G. Hess, R. Holz, M. Dauer, J. Raedle, F. Lammert, F. Grunhage

Date Published: 17th Mar 2017

Publication Type: Not specified

Pathophysiology and Management of Alcoholic Liver Disease: Update 2016.

Abstract (Expand)

Alcoholic liver disease (ALD) is a leading cause of cirrhosis, liver cancer, and acute and chronic liver failure and as such causes significant morbidity and mortality. While alcohol consumption is … slightly decreasing in several European countries, it is rising in others and remains high in many countries around the world. The pathophysiology of ALD is still incompletely understood but relates largely to the direct toxic effects of alcohol and its main intermediate, acetaldehyde. Recently, novel putative mechanisms have been identified in systematic scans covering the entire human genome and raise new hypotheses on previously unknown pathways. The latter also identify host genetic risk factors for significant liver injury, which may help design prognostic risk scores. The diagnosis of ALD is relatively easy with a panel of well-evaluated tests and only rarely requires a liver biopsy. Treatment of ALD is difficult and grounded in abstinence as the pivotal therapeutic goal; once cirrhosis is established, treatment largely resembles that of other etiologies of advanced liver damage. Liver transplantation is a sound option for carefully selected patients with cirrhosis and alcoholic hepatitis because relapse rates are low and prognosis is comparable to other etiologies. Still, many countries are restrictive in allocating donor livers for ALD patients. Overall, few therapeutic options exist for severe ALD. However, there is good evidence of benefit for only corticosteroids in severe alcoholic hepatitis, while most other efforts are of limited efficacy. Considering the immense burden of ALD worldwide, efforts of medical professionals and industry partners to develop targeted therapies in ALF has been disappointingly low.

Authors: F. Stickel, C. Datz, J. Hampe, R. Bataller

Date Published: 15th Mar 2017

Publication Type: Not specified

PEtab—Interoperable specification of parameter estimation problems in systems biology

Abstract

Not specified

Authors: Leonard Schmiester, Yannik Schälte, Frank T. Bergmann, Tacio Camba, Erika Dudkin, Janine Egert, Fabian Fröhlich, Lara Fuhrmann, Adrian L. Hauber, Svenja Kemmer, Polina Lakrisenko, Carolin Loos, Simon Merkt, Wolfgang Müller, Dilan Pathirana, Elba Raimúndez, Lukas Refisch, Marcus Rosenblatt, Paul L. Stapor, Philipp Städter, Dantong Wang, Franz-Georg Wieland, Julio R. Banga, Jens Timmer, Alejandro F. Villaverde, Sven Sahle, Clemens Kreutz, Jan Hasenauer, Daniel Weindl

Date Published: 26th Jan 2021

Publication Type: Journal

Pharmacokinetics and pharmacodynamics of thiopurines in an in vitro model of human hepatocytes: Insights from an innovative mass spectrometry assay.

Abstract (Expand)

AIM: To apply an innovative LC-MS/MS method to quantify thiopurine metabolites in human hepatocytes and to associate them to cytotoxicity. METHODS: Immortalized human hepatocytes (IHH cells) were treated … for 48 and 96 h, with 1.4 x 10(-4) M azathioprine and 1.1 x 10(-3) M mercaptopurine, concentrations corresponding to the IC50 values calculated after 96 h exposure in previous cytotoxicity analysis. After treatments, cells were collected for LC-MS/MS analysis to quantify 11 thiopurine metabolites with different level of phosphorylation and viable cells were counted by trypan blue exclusion assay to determine thiopurines in vitro effect on cell growth and survival. Statistical significance was determined by analysis of variance (ANOVA). RESULTS: Azathioprine and mercaptopurine had a significant time-dependent cytotoxic effect (p-value ANOVA = 0.012), with a viable cell count compared to controls of 55.5% and 67.5% respectively after 48 h and 23.7% and 36.1% after 96 h; no significant difference could be observed between the two drugs. Quantification of thiopurine metabolites evidenced that the most abundant metabolite was TIMP, representing 57.1% and 40.3% of total metabolites after 48 and 96 h. Total thiopurine metabolites absolute concentrations decreased over time: total mean content decreased from 469.9 pmol/million cells to 83.6 pmol/million cells (p-value ANOVA = 0.0070). However, considering the relative amount of thiopurine metabolites, TGMP content significantly increased from 11.4% cells to 26.4% (p-value ANOVA = 0.017). A significant association between thiopurine effects and viable cell counts could be detected only for MeTIMP: lower MeTIMP concentrations were associated with lower cell survival (p-value ANOVA = 0.011). Moreover, the ratio between MeTIMP and TGMP metabolites directly correlated with cell survival (p-value ANOVA = 0.037). CONCLUSION: Detailed quantification of thiopurine metabolites in a human hepatocytes model provided useful insights on the association between thioguanine and methyl-thioinosine nucleotides with cell viability.

Authors: M. Pelin, E. Genova, L. Fusco, M. Marisat, U. Hofmann, D. Favretto, M. Lucafo, A. Taddio, S. Martelossi, A. Ventura, G. Stocco, M. Schwab, G. Decorti

Date Published: 12th Aug 2017

Publication Type: Not specified

Physiologic Reduction of Hepatic Venous Blood Flow by the Valsalva Maneuver Decreases Liver Stiffness.

Abstract (Expand)

OBJECTIVES: Liver stiffness increases after intake of food or water, suggesting that hepatic venous blood flow affects the results of elastographic measurements. This study investigated the correlation … between in vivo liver stiffness and hepatic blood flow using the Valsalva maneuver for reducing intrahepatic venous blood flow. METHODS: Intrahepatic changes in venous blood flow were assessed by sonography based on the pulsed wave Doppler velocity, vessel diameter assessment, and blood flow volume measurements in the portal vein and right hepatic vein. Time-harmonic elastography at 7 harmonic driving frequencies (30-60 Hz) was used to measure liver stiffness in the right liver lobe of 15 healthy volunteers. RESULTS: The right hepatic vein diameter, flow volume, and peak pulsed wave velocity decreased during the Valsalva maneuver from mean +/- SD values of 8.64 +/- 1.85 to 6.55 +/- 1.84 mm (P = .002), 0.53 +/- 0.23 to 0.37 +/- 0.26 L/min (P = .037), and 22.14 +/- 4.87 to 17.38 +/- 5.41 cm/s (P = .01), respectively. This maneuver decreased liver stiffness in all volunteers by a mean of approximately 13% from 1.71 +/- 0.22 to 1.48 +/- 0.22 m/s (P = .00006). CONCLUSIONS: Our results demonstrate that liver stiffness is sensitive to altered venous blood flow, which is of clinical importance when using elastography for evaluation of portal hypertension. Furthermore, our results indicate that accurate measurement of liver stiffness requires standardized breathing conditions to rule out effects of changes in hepatic blood flow on elastographic findings.

Authors: S. Ipek-Ugay, H. Tzschatzsch, J. Braun, T. Fischer, I. Sack

Date Published: 20th Mar 2017

Publication Type: Not specified

Physiologically-based modelling in mice suggests an aggravated loss of clearance capacity after toxic liver damage

Abstract (Expand)

Diseases and toxins may lead to death of active liver tissue, resulting in a loss of total clearance capacity at the whole-body level. However, it remains difficult to study, whether the loss of … metabolizing tissue is sufficient to explain loss of metabolic capacity of the liver or whether the surviving tissue undergoes an adaptive response to compensate the loss. To understand the cellular impact of toxic liver damage in an in vivo situation, we here used physiologically-based pharmacokinetic modelling to investigate pharmacokinetics of a specifically designed drug cocktail at three different sampling sites of the body in healthy mice and mice treated with carbon tetrachloride (CCl4). Liver zonation was explicitly quantified in the models through immunostaining of cytochrome P450s enzymes. Comparative analyses between the simulated decrease in clearance capacity and the experimentally measured loss in tissue volume indicated that CCl4-induced impairment of metabolic functions goes beyond the mere loss of metabolically active tissue. The here established integrative modelling strategy hence provides mechanistic insights into functional consequences of toxic liver damage in an in vivo situation, which would not have been accessible by conventional methods.

Authors: Arne Schenk, Ahmed Ghallab, Ute Hofmann, Reham Hassan, Michael Schwarz, Andreas Schuppert, Lars Ole Schwen, Albert Braeuning, Donato Teutonico, Jan G. Hengstler, Lars Kuepfer

Date Published: 1st Dec 2017

Publication Type: Not specified

Physiologically-based modelling in mice suggests an aggravated loss of clearance capacity after toxic liver damage

Abstract

Not specified

Authors: Arne Schenk, Ahmed Ghallab, Ute Hofmann, Reham Hassan, Michael Schwarz, Andreas Schuppert, Lars Ole Schwen, Albert Braeuning, Donato Teutonico, Jan G. Hengstler, Lars Kuepfer

Date Published: 1st Dec 2017

Publication Type: Not specified

Pipe-3D: A Pipeline Based on Immunofluorescence, 3D Confocal Imaging, Reconstructions, and Morphometry for Biliary Network Analysis in Cholestasis

Abstract

Not specified

Authors: Amruta Damle-Vartak, Brigitte Begher-Tibbe, Georgia Gunther, Fabian Geisler, Nachiket Vartak, Jan G. Hengstler

Date Published: 2019

Publication Type: Book

PK-DB: PharmacoKinetics DataBase for Individualized and Stratified Computational Modeling

Abstract (Expand)

A multitude of pharmacokinetics studies have been published. However, due to the lack of an open database, pharmacokinetics data, as well as the corresponding meta-information, have been difficult to … access. We present PK-DB (https://pk-db.com), an open database for pharmacokinetics information from clinical trials including pre-clinical research. PK-DB provides curated information on (i) characteristics of studied patient cohorts and subjects (e.g. age, bodyweight, smoking status); (ii) applied interventions (e.g. dosing, substance, route of application); (iii) measured pharmacokinetic time-courses; (iv) pharmacokinetic parameters (e.g. clearance, half-life, area under the curve). Key features are the representation of experimental errors, the normalization of measurement units, annotation of information to biological ontologies, calculation of pharmacokinetic parameters from concentration-time profiles, a workflow for collaborative data curation, strong validation rules on the data, computational access via a REST API as well as human access via a web interface. PK-DB enables meta-analysis based on data from multiple studies and data integration with computational models. A special focus lies on meta-data relevant for individualized and stratified computational modeling with methods like physiologically based pharmacokinetic (PBPK), pharmacokinetic/pharmacodynamic (PK/DB), or population pharmacokinetic (pop PK) modeling.

Authors: Jan Grzegorzewski, Janosch Brandhorst, Dimitra Eleftheriadou, Kathleen Green, Matthias König

Date Published: 9th Sep 2019

Publication Type: Unpublished

PK-DB: pharmacokinetics database for individualized and stratified computational modeling.

Abstract (Expand)

A multitude of pharmacokinetics studies have been published. However, due to the lack of an open database, pharmacokinetics data, as well as the corresponding meta-information, have been difficult to … access. We present PK-DB (https://pk-db.com), an open database for pharmacokinetics information from clinical trials. PK-DB provides curated information on (i) characteristics of studied patient cohorts and subjects (e.g. age, bodyweight, smoking status, genetic variants); (ii) applied interventions (e.g. dosing, substance, route of application); (iii) pharmacokinetic parameters (e.g. clearance, half-life, area under the curve) and (iv) measured pharmacokinetic time-courses. Key features are the representation of experimental errors, the normalization of measurement units, annotation of information to biological ontologies, calculation of pharmacokinetic parameters from concentration-time profiles, a workflow for collaborative data curation, strong validation rules on the data, computational access via a REST API as well as human access via a web interface. PK-DB enables meta-analysis based on data from multiple studies and data integration with computational models. A special focus lies on meta-data relevant for individualized and stratified computational modeling with methods like physiologically based pharmacokinetic (PBPK), pharmacokinetic/pharmacodynamic (PK/PD), or population pharmacokinetic (pop PK) modeling.

Authors: J. Grzegorzewski, J. Brandhorst, K. Green, D. Eleftheriadou, Y. Duport, F. Barthorscht, A. Koller, D. Y. J. Ke, S. De Angelis, M. Konig

Date Published: 5th Nov 2020

Publication Type: Journal

Polymorphic variation in TPMT is the principal determinant of TPMT phenotype: A meta-analysis of three genome-wide association studies.

Abstract (Expand)

Thiopurine-related hematotoxicity in pediatric acute lymphoblastic leukemia (ALL) and inflammatory bowel diseases has been linked to genetically defined variability in thiopurine S-methyltransferase … (TPMT) activity. While gene testing of TPMT is being clinically implemented, it is unclear if additional genetic variation influences TPMT activity with consequences for thiopurine-related toxicity. To examine this possibility, we performed a genome-wide association study (GWAS) of red blood cell TPMT activity in 844 Estonian individuals and 245 pediatric ALL cases. Additionally, we correlated genome-wide genotypes to human hepatic TPMT activity in 123 samples. Only genetic variants mapping to chromosome 6, including the TPMT gene region, were significantly associated with TPMT activity (P < 5.0 x 10-8 ) in each of the three GWAS and a joint meta-analysis of 1,212 cases (top hit P = 1.2 x 10-72 ). This finding is consistent with TPMT genotype being the primary determinant of TPMT activity, reinforcing the rationale for genetic testing of TPMT alleles in routine clinical practice to individualize mercaptopurine dosage.

Authors: R. Tamm, R. Magi, R. Tremmel, S. Winter, E. Mihailov, A. Smid, A. Moricke, K. Klein, M. Schrappe, M. Stanulla, R. Houlston, R. Weinshilboum, I. Mlinaric Rascan, A. Metspalu, L. Milani, M. Schwab, E. Schaeffeler

Date Published: 23rd Oct 2016

Publication Type: Not specified

Predicting liver failure after extended right hepatectomy following right portal vein embolization with gadoxetic acid-enhanced MRI.

Abstract (Expand)

OBJECTIVES: Predicting post-hepatectomy liver failure (PHLF) after extended right hepatectomy following portal vein embolization (PVE) from serial gadoxetic acid-enhanced magnetic resonance imaging … (MRI). METHODS: Thirty-six patients who underwent hepatectomy following PVE were evaluated prospectively with gadoxetic acid-enhanced MRI examinations at predefined intervals during the course of their treatment, i.e., before and 14 days and 28 days after PVE as well as 10 days after hepatectomy. Relative enhancement (RE) and volume of the left and right liver lobes were determined. The study population was divided into two groups with respect to signs of PHLF. Differences between the two groups were assessed using the Mann-Whitney U test, and predictive parameters for group membership were investigated using ROC and logistic regression analysis. RESULTS: RE of the left lobe prior to PVE versus 14 days after PVE was significantly lower in patients with PHLF than in those without PHLF (Mann-Whitney U test p < 0.001) and proved to be the best predictor of PHLF in ROC analysis with an AUC of 0.854 (p < 0.001) and a cutoff value of - 0.044 with 75.0% sensitivity and 92.6% specificity. Consistent with this result, logistic linear regression analysis adjusted for age identified the same parameter to be a significant predictor of PHLF (p = 0.040). CONCLUSIONS: Gadoxetic acid-enhanced MRI performed as an imaging-based liver function test before and after PVE can help to predict PHLF. The risk of PHLF can be predicted as early as 14 days after PVE. KEY POINTS: * To predict the likelihood of post-hepatectomy liver failure, it is important to estimate not only future liver remnant volume prior to extended liver resection but also future liver remnant function. * Future liver remnant function can be predicted by performing gadoxetic acid-enhanced MRI as an imaging-based liver function test before and after portal vein embolization. * A reduction of relative enhancement of the liver in gadoxetic acid-enhanced MRI after portal vein embolization of 0.044 predicts post-hepatectomy liver failure with 75.0% sensitivity and 92.6% specificity.

Authors: D. Theilig, I. Steffen, M. Malinowski, M. Stockmann, D. Seehofer, J. Pratschke, B. Hamm, T. Denecke, D. Geisel

Date Published: 23rd Mar 2019

Publication Type: Not specified

Prediction of Multiple 3D Tissue Structures Based on Single-Marker Images Using Convolutional Neural Networks

Abstract (Expand)

A quantitative understanding of complex biological systems such as tissues requires reconstructing the structure of the different components of the system. Fluorescence microscopy provides the means … to visualize simultaneously several tissue components. However, it can be time consuming and is limited by the number of fluorescent markers that can be used. In this study, we describe a toolbox of algorithms based on convolutional neural networks for the prediction of 3D tissue structures by learning features embedded within single-marker images. As proof of principle, we aimed to predict the network of bile canaliculi (BC) in liver tissue using images of the cortical actin mesh as input. The actin meshwork has a characteristic organization in specific cellular domains, such as BC. However, the use of manually selected features from images of actin is not sufficient to properly reconstruct BC structure. Our deep learning framework showed a remarkable accuracy for the prediction of BC network and was successfully adapted (i.e. transfer learning) to predict the sinusoidal network. This approach allows for a complete reconstruction of tissue microarchitecture using a single fluorescent marker.

Authors: Hernan Morales-Navarrete, Fabian Segovia-Miranda, Marino Zerial, Yannis Kalaidzidis

Date Published: 1st Sep 2019

Publication Type: InProceedings

Predictive Power of Liver Maximum Function Capacity Test in Transjugular Intrahepatic Portosystemic Shunt Patients: A Pilot Study.

Abstract (Expand)

BACKGROUND: Transjugular intrahepatic shunt (TIPSS) is placed in patients with variceal bleeding, refractory ascites, and for other indications. Postprocedural liver function-associated complications … (LFAC), including hepatic encephalopathy (HE) and liver failure, represent a major setback. Current methods to predict complications are insufficient. OBJECTIVES: We investigated in a pilot study of patients prior TIPSS placement whether the risk of LFAC correlates with the functional reserve of the liver, as assessed by liver maximum function capacity (LiMAx) test. METHODS: Prospectively we included patients prior TIPSS placement between June 2016 and November 2017 at Saarland University Medical Center. LiMAx was conducted before and after TIPSS placement. Patients with HE prior TIPSS, as well as other factors predisposing to HE, including concomitant sedative drugs, current bacterial infections and sepsis, were excluded. Overt HE (OHE), LiMAx, and laboratory values were assessed before and after TIPSS placement. Data were analyzed in multivariate regression and AUROC models. RESULTS: Mean age was 60 +/- 8 years. Patients (n = 20) were mainly men (65%), and presented predominantly with Child-Pugh class B (90%). Indications for TIPSS were most commonly refractory ascites or recurrent variceal bleeding. In total, 40% of the patients developed LFAC after TIPSS placement. Expectedly, LiMAx decreased and serum bilirubin increased after TIPSS. LiMAx drop >/=20% was the only parameter predicting the development of LFAC after TIPSS in multivariate regression and AUROC analysis. CONCLUSIONS: In multivariate regression models and AUROC analysis, a drop in LiMAx predicted the development of LFAC after TIPSS placement. Additional larger studies assessing OHE and early liver failure separately are warranted.

Authors: M. C. Reichert, A. Schulz, A. Massmann, A. Buecker, M. Glanemann, F. Lammert, M. Malinowski

Date Published: 17th Oct 2019

Publication Type: Journal

Prospective Assessment of Liver Function by an Enzymatic Liver Function Test to Estimate Short-Term Survival in Patients with Liver Cirrhosis.

Abstract (Expand)

BACKGROUND: MELD attempts to objectively predict the risk of mortality of patients with liver cirrhosis and is commonly used to prioritize organ allocation. Despite the usefulness of the MELD, updated … metrics could further improve the accuracy of estimates of survival. AIMS: To assess and compare the prognostic ability of an enzymatic (13)C-based liver function test (LiMAx) and distinct markers of liver function to predict 3-month mortality of patients with chronic liver failure. METHODS: We prospectively investigated liver function of 268 chronic liver failure patients without hepatocellular carcinoma. Primary study endpoint was liver-related death within 3 months of follow-up. Prognostic values were calculated using Cox proportional hazards and logistic regression analysis. RESULTS: The Cox proportional hazard model indicated that LiMAx (p < 0.001) and serum creatinine values (p < 0.001) were the significant parameters independently associated with the risk of liver failure-related death. Logistic regression analysis revealed LiMAx and serum creatinine to be independent predictors of mortality. Areas under the receiver-operating characteristic curves for MELD (0.86 [0.80-0.92]) and for a combined score of LiMAx and serum creatinine (0.83 [0.76-0.90]) were comparable. CONCLUSIONS: Apart from serum creatinine levels, enzymatic liver function measured by LiMAx was found to be an independent predictor of short-term mortality risk in patients with liver cirrhosis. A risk score combining both determinants allows reliable prediction of short-term prognosis considering actual organ function. Trial Registration Number (German Clinical Trials Register) # DRKS00000614.

Authors: M. Jara, T. Dziodzio, M. Malinowski, K. Luttgert, R. Nikolov, P. V. Ritschl, R. Ollinger, J. Pratschke, M. Stockmann

Date Published: 9th Nov 2018

Publication Type: Not specified

Protective effects of statin therapy in cirrhosis are limited by a common SLCO1B1 transporter variant.

Abstract

Not specified

Author: Melissa Merkel, Christina Schneider, Robin Greinert, Alexander Zipprich, Cristina Ripoll, Frank Lammert1 and Matthias C. Reichert1

Date Published: No date defined

Publication Type: Journal

Protein modification with ISG15 blocks coxsackievirus pathology by antiviral and metabolic reprogramming.

Abstract (Expand)

Protein modification with ISG15 (ISGylation) represents a major type I IFN-induced antimicrobial system. Common mechanisms of action and species-specific aspects of ISGylation, however, are still ill … defined and controversial. We used a multiphasic coxsackievirus B3 (CV) infection model with a first wave resulting in hepatic injury of the liver, followed by a second wave culminating in cardiac damage. This study shows that ISGylation sets nonhematopoietic cells into a resistant state, being indispensable for CV control, which is accomplished by synergistic activity of ISG15 on antiviral IFIT1/3 proteins. Concurrent with altered energy demands, ISG15 also adapts liver metabolism during infection. Shotgun proteomics, in combination with metabolic network modeling, revealed that ISG15 increases the oxidative capacity and promotes gluconeogenesis in liver cells. Cells lacking the activity of the ISG15-specific protease USP18 exhibit increased resistance to clinically relevant CV strains, therefore suggesting that stabilizing ISGylation by inhibiting USP18 could be exploited for CV-associated human pathologies.

Authors: M. Kespohl, C. Bredow, K. Klingel, M. Voss, A. Paeschke, M. Zickler, W. Poller, Z. Kaya, J. Eckstein, H. Fechner, J. Spranger, M. Fahling, E. K. Wirth, L. Radoshevich, F. Thery, F. Impens, N. Berndt, K. P. Knobeloch, A. Beling

Date Published: 21st Mar 2020

Publication Type: Not specified

pSSAlib: The partial-propensity stochastic chemical network simulator

Abstract (Expand)

Chemical reaction networks are ubiquitous in biology, and their dynamics is fundamentally stochastic. Here, we present the software library pSSAlib, which provides a complete and concise implementation … of the most efficient partial-propensity methods for simulating exact stochastic chemical kinetics. pSSAlib can import models encoded in Systems Biology Markup Language, supports time delays in chemical reactions, and stochastic spatiotemporal reaction-diffusion systems. It also provides tools for statistical analysis of simulation results and supports multiple output formats. It has previously been used for studies of biochemical reaction pathways and to benchmark other stochastic simulation methods. Here, we describe pSSAlib in detail and apply it to a new model of the endocytic pathway in eukaryotic cells, leading to the discovery of a stochastic counterpart of the cut-out switch motif underlying early-to-late endosome conversion. pSSAlib is provided as a stand-alone command-line tool and as a developer API. We also provide a plug-in for the SBMLToolbox. The open-source code and pre-packaged installers are freely available from http://mosaic.mpi-cbg.de.

Authors: Oleksandr Ostrenko, Pietro Incardona, Rajesh Ramaswamy, Lutz Brusch, Ivo F. Sbalzarini

Date Published: 4th Dec 2017

Publication Type: Not specified

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