Publications by authors named "Mahdi Jalili"

70 Publications

Percolation of heterogeneous flows uncovers the bottlenecks of infrastructure networks.

Nat Commun 2021 02 23;12(1):1254. Epub 2021 Feb 23.

Mathematical Sciences, School of Science, RMIT University, Melbourne, VIC, Australia.

Whether it be the passengers' mobility demand in transportation systems, or the consumers' energy demand in power grids, the primary purpose of many infrastructure networks is to best serve this flow demand. In reality, the volume of flow demand fluctuates unevenly across complex networks while simultaneously being hindered by some form of congestion or overload. Nevertheless, there is little known about how the heterogeneity of flow demand influences the network flow dynamics under congestion. To explore this, we introduce a percolation-based network analysis framework underpinned by flow heterogeneity. Thereby, we theoretically identify bottleneck links with guaranteed decisive impact on how flows are passed through the network. The effectiveness of the framework is demonstrated on large-scale real transportation networks, where mitigating the congestion on a small fraction of the links identified as bottlenecks results in a significant network improvement.
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http://dx.doi.org/10.1038/s41467-021-21483-yDOI Listing
February 2021

Appropriate time to apply control input to complex dynamical systems.

Sci Rep 2020 12 16;10(1):22035. Epub 2020 Dec 16.

Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

Controlling a network structure has many potential applications many fields. In order to have an effective network control, not only finding good driver nodes is important, but also finding the optimal time to apply the external control signals to network nodes has a critical role. If applied in an appropriate time, one might be to control a network with a smaller control signals, and thus less energy. In this manuscript, we show that there is a relationship between the strength of the internal fluxes and the effectiveness of the external control signal. To be more effective, external control signals should be applied when the strength of the internal states is the smallest. We validate this claim on synthetic networks as well as a number of real networks. Our results may have important implications in systems medicine, in order to find the most appropriate time to inject drugs as a signal to control diseases.
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http://dx.doi.org/10.1038/s41598-020-78909-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744535PMC
December 2020

Activation of Functional Brain Networks in Children With Psychogenic Non-epileptic Seizures.

Front Hum Neurosci 2020 25;14:339. Epub 2020 Aug 25.

Department of Psychological Medicine, The Children's Hospital at Westmead, Sydney, NSW, Australia.

Objectives: Psychogenic non-epileptic seizures (PNES) have been hypothesized to emerge in the context of neural networks instability. To explore this hypothesis in children, we applied a graph theory approach to examine connectivity in neural networks in the resting-state EEG in 35 children with PNES, 31 children with other functional neurological symptoms (but no PNES), and 75 healthy controls.

Methods: The networks were extracted from Laplacian-transformed time series by a coherence connectivity estimation method.

Results: Children with PNES (vs. controls) showed widespread changes in network metrics: increased global efficiency (gamma and beta bands), increased local efficiency (gamma band), and increased modularity (gamma and alpha bands). Compared to controls, they also had higher levels of autonomic arousal (e.g., lower heart variability); more anxiety, depression, and stress on the Depression Anxiety and Stress Scales; and more adverse childhood experiences on the Early Life Stress Questionnaire. Increases in network metrics correlated with arousal. Children with other functional neurological symptoms (but no PNES) showed scattered and less pronounced changes in network metrics.

Conclusion: The results indicate that children with PNES present with increased activation of neural networks coupled with increased physiological arousal. While this shift in functional organization may confer a short-term adaptive advantage-one that facilitates neural communication and the child's capacity to respond self-protectively in the face of stressful life events-it may also have a significant biological cost. It may predispose the child's neural networks to periods of instability-presenting clinically as PNES-when the neural networks are faced with perturbations in energy flow or with additional demands.
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http://dx.doi.org/10.3389/fnhum.2020.00339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477327PMC
August 2020

Target controllability with minimal mediators in complex biological networks.

Genomics 2020 11 6;112(6):4938-4944. Epub 2020 Sep 6.

Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. Electronic address:

Controllability of a complex network system is related to finding a set of minimum number of nodes, known as drivers, controlling which allows having a full control on the dynamics of the network. For some applications, only a portion of the network is required to be controlled, for which target control has been proposed. Often, along the controlling route from driver nodes to target nodes, some mediators (intermediate nodes) are also unwillingly controlled, which might cause various side effects. In controlling cancerous cells, unwillingly controlling healthy cells, might result in weakening them, thus affecting the immune system against cancer. This manuscript proposes a suitable candidate solution to the problem of finding minimum number of driver nodes under minimal mediators. Although many others have attempted to develop algorithms to find minimum number of drivers for target control, the newly proposed algorithm is the first one that is capable of achieving this goal and at the same time, keeping the number of the mediators to a minimum. The proposed controllability condition, based on path lengths between node pairs, meets Kalman's controllability rank condition and can be applied on directed networks. Our results show that the path length is a major determinant of in properties of the target control under minimal mediators. As the average path length becomes larger, the ratio of drivers to target nodes decreases and the ratio of mediators to targets increases. The proposed methodology has potential applications in biological networks. The source code of the algorithm and the networks that have been used are available from the following link: https://github.com/LBBSoft/Target-Control-with-Minimal-Mediators.git.
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http://dx.doi.org/10.1016/j.ygeno.2020.09.003DOI Listing
November 2020

Outcome of peripheral blood allogeneic hematopoietic stem cell transplantation as a treatment option in patients with severe aplastic anemia between 40 and 50 years.

Hematol Oncol Stem Cell Ther 2020 Jul 3. Epub 2020 Jul 3.

Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

The frontline treatment for patients younger than 40 years with severe aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-identical sibling donor. However, in patients with severe AA who are older than 40 years, allogeneic HSCT has been found to be associated with increased treatment-related mortality and toxicity, even when matched sibling donors are used. We report our institutional experience with allogeneic HSCT in patients with severe AA between 40 and 50 years. A total of 19 patients with severe AA were included in the study. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. The mean age of patients at the time of transplant was 43.79 years, and 57.9% were male. The mortality rate was 36.8%, attributed to infection (10.5%), relapse (15.8%), and renal failure (5.3%) in all cases. Acute graft-versus-host disease (GVHD) occurred in five patients (26.3%), and chronic GVHD occurred in two patients (10.5%). The 5-year OS was 62% and the 5-year DFS was 52%. We found that the patient's age, platelet level prior to transplantation, and the number of CD3 cells infused for each transplant were independent prognostic factors for OS, and the age and sex of the patient, graft rejection, and platelet level prior to transplantation were significant prognostic factors associated with DFS. We recommend that immunosuppressive therapy be considered as a first-line treatment in patients with severe AA who are older than 40 years. Allogeneic HSCT can be considered a valid alternative option in patients whose suppression therapy fails.
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http://dx.doi.org/10.1016/j.hemonc.2020.06.004DOI Listing
July 2020

An alternative test for determining autologous stem cell transplantation cell harvesting outcome: Comparison between predictive values of two tests.

Transfus Apher Sci 2020 Aug 27;59(4):102763. Epub 2020 Mar 27.

Transfusion Medicine Unit, Cochin Hospital, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France. Electronic address:

Daily CD34+ cells enumeration as a success indicator of stem cell pheresis procedure using flow cytometry is costly, lengthy, and labor-intensive. Thus, finding a simpler method to achieve the optimum time for harvesting the minimum required stem cells for transplantation could be helpful. The aim of this study was to evaluate the predictive value of reticulocytes fractions and their sensesivity and specificity in guiding CD34+ cell harvesting by G-CSF mobilization strategy. In this study, 49 candidates for autologous peripheral blood stem cell transplantation were enrolled. Before leukapheresis, the immature reticulocytes fraction (IRF) and CD34+ cell count were measured. Moreover, patients were evaluated for leukapheresis outcomes in two MNC and cMNC groups. Here we demonstrated that IRF, LFR, and MFR with the associated criterion of >17.3, ≤82.5, and >15.9, respectively, earned 100 % specificity and 47.2 %, 47.22 %, and 41.46 % sensitivity to predict the minimum required CD34+ cell count. Furthermore, IRF-V (Value) and MFR-V with the associated criterion of >0.77 and >0.55, respectively, earned 58.33 %, 66.67 % sensitivity and 84.62 %, 69.23 % of specificity, separately. As only MFR-V was able to predict the platelet engraftment (P-value = 0.014), none of the other above mentioned factors were not able to predict the neutrophil engraftment. Likewise, it was shown that patients who underwent MNC leukapheresis had a statistically significantly higher total WBC, harvested CD34 cells, MNCs/ kg, and lower apheresis durations (P-values<0.05). Taken together, using IRF and its maturity stages seems to be a compelling predictor of minimal required CD34+ cells in autologous peripheral blood stem cell transplantation.
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http://dx.doi.org/10.1016/j.transci.2020.102763DOI Listing
August 2020

GEMtractor: extracting views into genome-scale metabolic models.

Bioinformatics 2020 05;36(10):3281-3282

Department of Systems Biology and Bioinformatics, University of Rostock, 18051 Rostock, Germany.

Summary: Computational metabolic models typically encode for graphs of species, reactions and enzymes. Comparing genome-scale models through topological analysis of multipartite graphs is challenging. However, in many practical cases it is not necessary to compare the full networks. The GEMtractor is a web-based tool to trim models encoded in SBML. It can be used to extract subnetworks, for example focusing on reaction- and enzyme-centric views into the model.

Availability And Implementation: The GEMtractor is licensed under the terms of GPLv3 and developed at github.com/binfalse/GEMtractor-a public version is available at sbi.uni-rostock.de/gemtractor.
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http://dx.doi.org/10.1093/bioinformatics/btaa068DOI Listing
May 2020

Application of hyperbolic geometry in link prediction of multiplex networks.

Sci Rep 2019 08 30;9(1):12604. Epub 2019 Aug 30.

School of Engineering, RMIT University, Melbourne, Australia.

Recently multilayer networks are introduced to model real systems. In these models the individuals make connection in multiple layers. Transportation networks, biological systems and social networks are some examples of multilayer networks. There are various link prediction algorithms for single-layer networks and some of them have been recently extended to multilayer networks. In this manuscript, we propose a new link prediction algorithm for multiplex networks using two novel similarity metrics based on the hyperbolic distance of node pairs. We use the proposed methods to predict spurious and missing links in multiplex networks. Missing links are those links that may appear in the future evolution of the network, while spurious links are the existing connections that are unlikely to appear if the network is evolving normally. One may interpret spurious links as abnormal links in the network. We apply the proposed algorithm on real-world multiplex networks and the numerical simulations reveal its superiority than the state-of-the-art algorithms.
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http://dx.doi.org/10.1038/s41598-019-49001-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717198PMC
August 2019

Optimization of Communication Network Topology in Distributed Control Systems Subject to Prescribed Decay Rate.

IEEE Trans Cybern 2019 Jul 18. Epub 2019 Jul 18.

In this paper, we propose a simple cohesive framework to find an optimal directed control network topology with minimum number of links while a prescribed decay rate is satisfied in the transient response of a distributed control system. In order to guarantee the system's decay rate to be faster than a prespecified value, a constraint on the dominant eigenvalue of the system is required to be considered. This results in a nonconvex optimization problem as eigenvalue of a parametric nonsymmetric matrix is a nonconvex, nonsmooth, and even non-Lipschitz function. Here, we present a convex equivalent optimization problem whose minimizer also solves this eigenvalue optimization problem. This optimization problem proposes a state-feedback matrix which results in a decay rate faster than a given value while input signal costs are considered. The equivalent optimization problem in combination with sparsity-promoting optimal control constitutes a combinatorial optimization problem. Using alternating direction method of multipliers, the problem is decomposed into a chain of analytically solvable subproblems which are differentiable and separable. The proposed optimization framework includes relative preference between the topology of the control network and the decay rate of the system. The simulation results show the effectiveness of the proposed framework.
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http://dx.doi.org/10.1109/TCYB.2019.2926386DOI Listing
July 2019

Peripheral blood stem cell apheresis in low-weight children: A single centre study.

Transfus Apher Sci 2019 Jun 19;58(3):300-303. Epub 2019 Apr 19.

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran; Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Tehran, Iran.

Peripheral blood stem cell transplantation (PBSCT) is now widely used in both malignant and non-malignant hematologic diseases as a treatment strategy. Using this approach, a controversial group of donors is children weighing 20 kg or less. The aim of this study was to evaluate results of allogeneic and autologous PBSCT and also the efficacy of our suggested alternative method for a custom prime in cell harvesting of this group. All the participants' demographic and laboratory data were collected before apheresis. A total of 37 individuals participated in this study of which 12 and 25 of them were categorized in autologous and allogeneic groups respectively. For the apheresis procedure, a central venous access was used as well as the custom prime method with some changes. Apheresis details, as well as CD34 and CD3 cell counts in the allogeneic and autologous groups, were calculated. In this study, 91.9% (N = 34) of all individuals achieved the minimal amount of cells for PBSCT (2 × 10 CD34 cells/kg) in one session. On the other hand, 12% (N = 3) of donors in the allogeneic group achieved the minimal threshold in 2 apheresis sessions. During the leukapheresis a total processed blood volume/total blood volume ratio (TPBV/TBV) was calculated as 4.64 ± 1.06 and 5.18 ± 0.73 fold in the allogeneic and autologous groups respectively. The mean of harvested CD34 cells in allogeneic and autologous groups was 5.28 ± 3.47 × 10 and 3.57 ± 2.9 × 10 cells/kg respectively. Likewise, in the allogeneic group, the mean of the harvested CD3 cell count was 339 ± 141 × 10/kg. Also, the median day of white blood cell (WBC) engraftment was 14 and 13 for allogeneic and autologous groups respectively. Furthermore, the median day of platelet engraftment was 19.5 for both allogeneic and autologous groups. Among the recipients of the allogeneic group, acute graft versus host disease (aGVHD) was detected in 56% (N = 14) of patients and this was also correct for chronic GVHD. Taken together, it was shown, despite the probable complications of peripheral blood stem cell apheresis in donors weighing less than 20 kg; that it is possible to perform this procedure without any complication during the leukapheresis.
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http://dx.doi.org/10.1016/j.transci.2019.04.018DOI Listing
June 2019

Altered expression of lncRNA in chronic lymphocytic leukemia patients, correlation with cytogenetic findings.

Blood Res 2018 Dec 17;53(4):320-324. Epub 2018 Dec 17.

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran, Iran.

Background: Recent studies have devoted much attention to non-protein-coding transcripts in relation to a wide range of malignancies. , a long non-coding RNA, has been reported to be associated with cancer progression and prognosis. Thus, we here determined gene expression in chronic lymphocytic leukemia (CLL), a genetically heterogeneous disease, and explored its possible relationships with cytogenetic abnormalities.

Methods: expression level was evaluated using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) on blood mononuclear cells from 30 non-treated CLL patients and 30 matched healthy controls. Cytogenetic abnormalities were determined in patients by fluorescence in situ hybridization (FISH).

Results: expression level was up-regulated in the CLL group compared to healthy controls (=0.008). Del13q14, followed by Del11q22, were the most prevalent cytogenetic abnormalities. We found no association between the FISH results and expression in patients.

Conclusion: Altered expression of is associated with CLL development. Further investigations are required to assess the relationship between this long non-coding RNA and CLL patient survival and prognosis.
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http://dx.doi.org/10.5045/br.2018.53.4.320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300670PMC
December 2018

Robust Second-Order Consensus Using a Fixed-Time Convergent Sliding Surface in Multiagent Systems.

IEEE Trans Cybern 2020 Feb 30;50(2):846-855. Epub 2018 Oct 30.

Faster convergence is always sought in many applications. Designing fixed-time control has recently gained much attention since, for this type of control structure, the convergence time of the states does not depend on initial conditions, unlike other control methods providing faster convergence. This paper proposes a new distributed algorithm for second-order consensus in multiagent systems by using a full-order fixed-time convergent sliding surface. The stability analysis is performed using the Lyapunov function and bi-homogenous property. Moreover, the proposed control is smooth and free from any singularity. The robustness of the proposed scheme is verified both in the presence of Lipschitz disturbances and uncertainties in the network. The proposed method is compared with a state-of-the-art method to show the effectiveness.
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http://dx.doi.org/10.1109/TCYB.2018.2875362DOI Listing
February 2020

Expression Analysis of PVT1, CCDC26, and CCAT1 Long Noncoding RNAs in Acute Myeloid Leukemia Patients.

Genet Test Mol Biomarkers 2018 Oct 14;22(10):593-598. Epub 2018 Sep 14.

1 Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences , Tehran, Iran .

Background: Recent evidence indicates that the PVT1, CCDC26, and CCAT1 long noncoding RNAs (lncRNAs) are involved in the leukemogenic process. This study quantified the expression levels of the PVT1, CCDC26, and CCAT1 lncRNAs in patients with acute myeloid leukemia (AML) and also correlated their expression levels with the clinicopathological features of the patients.

Materials And Methods: The expression levels of the PVT1, CCDC26, and CCAT1 lncRNAs were analyzed using quantitative reverse transcription-polymerase chain reaction of bone marrow specimens obtained from 86 AML patients, 48 AML-M3 patients, and 40 normal controls.

Results: No differences were found between the combined AML patient populations and the healthy controls with respect to the expression levels of PVT1, CCDC26, and CCAT1 (p = 0.35, p = 0.09, and p = 0.77, respectively). However, compared with the controls, the AML-M3 patients had higher PVT1 expression (p = 0.017). Furthermore, high-risk AML-M3 patients manifested higher expression levels of PVT1 than low- and intermediate-risk groups. In addition, distinctive CCDC26 and CCAT1 expression levels were observed among patients with different French-American-British subtypes (p = 0.001 for CCDC26 and p = 0.013 for CCAT1). Compared with the healthy controls, AML-M4 and M5 had higher CCAT1 expression (p = 0.04) and AML-M2 and AML-M4/M5 patients had higher CCDC26 expression (p < 0.001 and p = 0.02, respectively). In addition, different patterns of CCDC26 expression were found among the different cytogenetic risk subtypes (p = 0.005). Finally, patients with intermediate cytogenetic risk showed higher CCDC26 expression levels.

Conclusion: The differential expression of the PVT1, CCDC26, and CCAT1 lncRNAs in different AML subtypes suggests that the deregulation of these transcripts may function in the multistep leukemogenic process and that they may serve as new therapeutic targets for this malignancy.
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http://dx.doi.org/10.1089/gtmb.2018.0143DOI Listing
October 2018

Information Spread and Topic Diffusion in Heterogeneous Information Networks.

Sci Rep 2018 Jun 22;8(1):9549. Epub 2018 Jun 22.

School of Engineering RMIT University, Melbourne, Australia.

Diffusion of information in complex networks largely depends on the network structure. Recent studies have mainly addressed information diffusion in homogeneous networks where there is only a single type of nodes and edges. However, some real-world networks consist of heterogeneous types of nodes and edges. In this manuscript, we model information diffusion in heterogeneous information networks, and use interactions of different meta-paths to predict the diffusion process. A meta-path is a path between nodes across different layers of a heterogeneous network. As its most important feature the proposed method is capable of determining the influence of all meta-paths on the diffusion process. A conditional probability is used assuming interdependent relations between the nodes to calculate the activation probability of each node. As independent cascade models, we consider linear threshold and independent cascade models. Applying the proposed method on two real heterogeneous networks reveals its effectiveness and superior performance over state-of-the-art methods.
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http://dx.doi.org/10.1038/s41598-018-27385-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040177PMC
June 2018

FLT3-ITD Compared with DNMT3A R882 Mutation Is a More Powerful Independent Inferior Prognostic Factor in Adult Acute Myeloid Leukemia Patients After Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study

Turk J Haematol 2018 08 22;35(3):158-167. Epub 2018 May 22.

Tehran University of Medical Sciences, Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center; Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran, Iran

Objective: This study aimed to evaluate DNMT3A exon 23 mutations and their prognostic impacts in the presence of NPM1 and FLT3 mutations in acute myeloid leukemia (AML) patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT).

Materials And Methods: This study comprised 128 adult AML patients referred to the Hematology-Oncology and Stem Cell Research Center of Shariati Hospital. NPM1 and FLT3-ITD mutations were detected by fragment analysis. For DNMT3A exon 23 mutation analysis, we used Sanger sequencing. Overall survival (OS) and relapse-free survival (RFS) curves were estimated by the Kaplan-Meier method and the log-rank test was used to calculate differences between groups.

Results: The prevalence of DNMT3A exon 23 mutations was 15.6% and hotspot region R882 mutations were prominent. RFS and OS were compared in patients with and without DNMT3A exon 23 mutations using univariate analysis and there was no significant difference between these groups of patients. On the contrary, the FLT3-ITD mutation significantly reduced the OS (p=0.009) and RFS (p=0.006) in AML patients after allogeneic HSCT. In the next step, patients with AML were divided into four groups regarding FLT3-ITD and DNMT3A mutations. Patients with DNMT3A R882mut/FLT3-ITDpos had the worst OS and RFS. These results indicate that DNMT3A mutations alone do not affect the clinical outcomes of AML patients undergoing allogeneic HSCT, but when accompanied by FLT3-ITD mutations, the OS was significantly reduced (5-year OS 0% for DNMT3A R882mut/FLT3-ITDpos patients vs. 62% DNMT3A R882wt/FLT3-ITDneg, p=0.025) and the relapse rate increased.

Conclusion: It can be deduced that DNMT3A R882mut/FLT3-ITDpos is an unfavorable prognostic factor in AML patients even after allogeneic HSCT.
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http://dx.doi.org/10.4274/tjh.2018.0017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110452PMC
August 2018

Prognostic Value of RUNX1 Mutations in AML: A Meta-Analysis

Asian Pac J Cancer Prev 2018 Feb 26;19(2):325-329. Epub 2018 Feb 26.

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The RUNX1 (AML1) gene is a relatively infrequent mutational target in cases of acute myeloid leukemia (AML). Previous work indicated that RUNX1 mutations can have pathological and prognostic implications. To evaluate prognostic value, we conducted a meta-analysis of 4 previous published works with data for survival according to RUNX1 mutation status. Pooled hazard ratios for overall survival and disease-free survival were 1.55 (95% confidence interval (CI) = 1.11–2.15; p-value = 0.01) and 1.76 (95% CI = 1.24–2.52; p-value = 0.002), respectively, for cases positive for RUNX1 mutations. This evidence supports clinical implications of RUNX1 mutations in the development and progression of AML cases and points to the possibility of a distinct category within the newer WHO classification. Though it must be kept in mind that the present work was based on data extracted from observational studies, the findings suggest that the RUNX1 status can contribute to risk-stratification and decision-making in management of AML.
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http://dx.doi.org/10.22034/APJCP.2018.19.2.325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980915PMC
February 2018

Unveiling network-based functional features through integration of gene expression into protein networks.

Biochim Biophys Acta Mol Basis Dis 2018 Jun 18;1864(6 Pt B):2349-2359. Epub 2018 Feb 18.

Department of Systems Biology and Bioinformatics, University of Rostock, 18051 Rostock, Germany. Electronic address:

Decoding health and disease phenotypes is one of the fundamental objectives in biomedicine. Whereas high-throughput omics approaches are available, it is evident that any single omics approach might not be adequate to capture the complexity of phenotypes. Therefore, integrated multi-omics approaches have been used to unravel genotype-phenotype relationships such as global regulatory mechanisms and complex metabolic networks in different eukaryotic organisms. Some of the progress and challenges associated with integrated omics studies have been reviewed previously in comprehensive studies. In this work, we highlight and review the progress, challenges and advantages associated with emerging approaches, integrating gene expression and protein-protein interaction networks to unravel network-based functional features. This includes identifying disease related genes, gene prioritization, clustering protein interactions, developing the modules, extract active subnetworks and static protein complexes or dynamic/temporal protein complexes. We also discuss how these approaches contribute to our understanding of the biology of complex traits and diseases. This article is part of a Special Issue entitled: Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.
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http://dx.doi.org/10.1016/j.bbadis.2018.02.010DOI Listing
June 2018

Enhancing response coordination through the assessment of response network structural dynamics.

PLoS One 2018 15;13(2):e0191130. Epub 2018 Feb 15.

Dept. of Computer Science and Eng., Sejong University, Seoul, Republic of Korea.

Preparing for intensifying threats of emergencies in unexpected, dangerous, and serious natural or man-made events, and consequent management of the situation, is highly demanding in terms of coordinating the personnel and resources to support human lives and the environment. This necessitates prompt action to manage the uncertainties and risks imposed by such extreme events, which requires collaborative operation among different stakeholders (i.e., the personnel from both the state and local communities). This research aims to find a way to enhance the coordination of multi-organizational response operations. To do so, this manuscript investigates the role of participants in the formed coordination response network and also the emergence and temporal dynamics of the network. By analyzing an inter-personal response coordination operation to an extreme bushfire event, the networks' and participants' structural change is evaluated during the evolution of the operation network over four time durations. The results reveal that the coordination response network becomes more decentralized over time due to the high volume of communication required to exchange information. New emerging communication structures often do not fit the developed plans, which stress the need for coordination by feedback in addition to by plan. In addition, we find that the participant's brokering role in the response operation network identifies a formal and informal coordination role. This is useful for comparison of network structures to examine whether what really happens during response operations complies with the initial policy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191130PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813905PMC
March 2018

Comparison of induction therapy in non-high risk acute promyelocytic leukemia with arsenic trioxide or in combination with ATRA.

Leuk Res 2018 03 3;66:85-88. Epub 2018 Feb 3.

Hematology-Oncology and Stem Cell Transplantation Research Center/Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Acute promyelocytic leukemia (APL) is a curable form of acute myeloid leukemia; in recent years, the use of new treatment strategies, such as combination therapy, have led to improved APL outcomes. Here, outcomes of patients treated with a combination of arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) are compared against patients treated with single ATO therapy.

Patients And Methods: In total, 67 patients with non-high-risk APL were evaluated. A group of 30 patients received ATO, and another group of 37 patients received ATO plus ATRA. ATO infusion at a dose of 0.15 mg/kg/day was continued till complete remission was achieved or till 60 days of consumption, and after 28 days of rest, second ATO course was initiated for 28 days as consolidation. Four courses separated by 28-day rest were planned. In the second group, 45 mg/m/day ATRA was added to ATO protocol.

Results: All patients except one in the ATO group and all patients in the ATO plus ATRA group were alive after a median follow-up of 18 and 17 months, respectively; 2.5-year overall survival in the ATO group was 86% (p-value = .32). Five patients in the ATO group experienced relapse, and 2.5-year leukemia-free survival in this group was 60%. No relapse occurred in the ATO plus ATRA group (p-value = .01). Differences in the mean of white blood cell (p-value = .67), platelet (p-value = .15), liver (p-value = .37), and renal (p-value = .95) dysfunctions were not significant.

Conclusion: Although ATO has been considered a first-line therapy in patients with APL, several studies have reported improved outcomes with a combination of ATO plus ATRA. This study demonstrated a significant decrease in relapse with this combination compared with single ATO therapy and supported the importance of ATRA in APL treatment.
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http://dx.doi.org/10.1016/j.leukres.2018.01.019DOI Listing
March 2018

Network biology: Describing biological systems by complex networks: Comment on "Network science of biological systems at different scales: A review" by M. Gosak et al.

Authors:
Mahdi Jalili

Phys Life Rev 2018 03 20;24:159-161. Epub 2017 Dec 20.

School of Engineering, RMIT University, Melbourne, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.plrev.2017.12.003DOI Listing
March 2018

Liver fibrosis alleviation after co-transplantation of hematopoietic stem cells with mesenchymal stem cells in patients with thalassemia major.

Ann Hematol 2018 Feb 17;97(2):327-334. Epub 2017 Nov 17.

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Kargar Shomali Ave, Shariati Hospital, Tehran, Iran.

The aims of this study are to determine the replacement rate of damaged hepatocytes by donor-derived cells in sex-mismatched recipient patients with thalassemia major and to determine whether co-transplantation of mesenchymal stem cells and hematopoietic stem cells (HSCs) can alleviate liver fibrosis. Ten sex-mismatched donor-recipient pairs who received co-transplantation of HSCs with mesenchymal stem cells were included in our study. Liver biopsy was performed before transplantation. Two other liver biopsies were performed between 2 and 5 years after transplantation. The specimens were studied for the presence of donor-derived epithelial cells or hepatocytes using fluorescence in situ hybridization by X- and Y-centromeric probes and immunohistochemical staining for pancytokeratin, CD45, and a hepatocyte-specific antigen. All sex-mismatched tissue samples demonstrated donor-derived hepatocyte independent of donor gender. XY-positive epithelial cells or hepatocytes accounted for 11 to 25% of the cells in histologic sections of female recipients in the first follow-up. It rose to 47-95% in the second follow-up. Although not statistically significant, four out of ten patients showed signs of improvement in liver fibrosis. Our results showed that co-transplantation of HSC with mesenchymal stem cells increases the rate of replacement of recipient hepatocytes by donor-derived cells and may improve liver fibrosis.
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http://dx.doi.org/10.1007/s00277-017-3181-9DOI Listing
February 2018

Comprehensive functional enrichment analysis of male infertility.

Sci Rep 2017 Nov 17;7(1):15778. Epub 2017 Nov 17.

Department of Systems Biology and Bioinformatics, University of Rostock, 18051, Rostock, Germany.

Spermatogenesis is a multifactorial process that forms differentiated sperm cells in a complex microenvironment. This process involves the genome, epigenome, transcriptome, and proteome to ensure the stability of the spermatogonia and supporting cells. The identification of signaling pathways linked to infertility has been hampered by the inherent complexity and multifactorial aspects of spermatogenesis. Systems biology is a promising approach to unveil underlying signaling pathways and genes and identify putative biomarkers. In this study, we analyzed thirteen microarray libraries of infertile humans and mice, and different classes of male infertility were compared using differentially expressed genes and functional enrichment analysis. We found regulatory processes, immune response, glutathione transferase and muscle tissue development to be among the most common biological processes in up-regulated genes, and genes involved in spermatogenesis were down-regulated in maturation arrest (MArrest) and oligospermia cases. We also observed the overexpression of genes involved in steroid metabolism in post-meiotic and meiotic arrest. Furthermore, we found that the infertile mouse model most similar to human MArrest was the Dazap1 mutant mouse. The results of this study could help elucidate features of infertility etiology and provide the basis for diagnostic markers.
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http://dx.doi.org/10.1038/s41598-017-16005-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693951PMC
November 2017

Shortest Paths in Multiplex Networks.

Sci Rep 2017 05 12;7(1):2142. Epub 2017 May 12.

School of Engineering, RMIT University, Melbourne, Australia.

The shortest path problem is one of the most fundamental networks optimization problems. Nowadays, individuals interact in extraordinarily numerous ways through their offline and online life (e.g., co-authorship, co-workership, or retweet relation in Twitter). These interactions have two key features. First, they have a heterogeneous nature, and second, they have different strengths that are weighted based on their degree of intimacy, trustworthiness, service exchange or influence among individuals. These networks are known as multiplex networks. To our knowledge, none of the previous shortest path definitions on social interactions have properly reflected these features. In this work, we introduce a new distance measure in multiplex networks based on the concept of Pareto efficiency taking both heterogeneity and weighted nature of relations into account. We then model the problem of finding the whole set of paths as a form of multiple objective decision making and propose an exact algorithm for that. The method is evaluated on five real-world datasets to test the impact of considering weights and multiplexity in the resulting shortest paths. As an application to find the most influential nodes, we redefine the concept of betweenness centrality based on the proposed shortest paths and evaluate it on a real-world dataset from two-layer trade relation among countries between years 2000 and 2015.
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http://dx.doi.org/10.1038/s41598-017-01655-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438413PMC
May 2017

Link prediction in multiplex online social networks.

R Soc Open Sci 2017 Feb 8;4(2):160863. Epub 2017 Feb 8.

Faculty of Natural Sciences and Mathematics, University of Maribor, Maribor, Slovenia; Center for Applied Mathematics and Theoretical Physics, University of Maribor, Maribor, Slovenia.

Online social networks play a major role in modern societies, and they have shaped the way social relationships evolve. Link prediction in social networks has many potential applications such as recommending new items to users, friendship suggestion and discovering spurious connections. Many real social networks evolve the connections in multiple layers (e.g. multiple social networking platforms). In this article, we study the link prediction problem in multiplex networks. As an example, we consider a multiplex network of Twitter (as a microblogging service) and Foursquare (as a location-based social network). We consider social networks of the same users in these two platforms and develop a meta-path-based algorithm for predicting the links. The connectivity information of the two layers is used to predict the links in Foursquare network. Three classical classifiers (naive Bayes, support vector machines (SVM) and K-nearest neighbour) are used for the classification task. Although the networks are not highly correlated in the layers, our experiments show that including the cross-layer information significantly improves the prediction performance. The SVM classifier results in the best performance with an average accuracy of 89%.
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http://dx.doi.org/10.1098/rsos.160863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367313PMC
February 2017

Meta-Analysis of Gene Expression Profiles in Acute Promyelocytic Leukemia Reveals Involved Pathways.

Int J Hematol Oncol Stem Cell Res 2017 Jan;11(1):1-12

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Acute promyelocytic leukemia (APL) is a unique subtype of acute leukemia. APL is a curable disease; however, drug resistance, early mortality, disease relapse and treatment-related complications remain challenges in APL patient management. One issue underlying these challenges is that the molecular mechanisms of the disease are not sufficiently understood. In this study, we performed a meta-analysis of gene expression profiles derived from microarray experiments and explored the background of disease by functional and pathway analysis. Our analysis revealed a gene signature with 406 genes that are up or down-regulated in APL. The pathway analysis determined that MAPK pathway and its involved elements such as JUN gene and AP-1 play important roles in APL pathogenesis along with insulin-like growth factor-binding protein-7. The results of this meta-analysis could be useful for developing more effective therapy strategies and new targets for diagnosis and drugs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338275PMC
January 2017

Evolution of Centrality Measurements for the Detection of Essential Proteins in Biological Networks.

Front Physiol 2016 26;7:375. Epub 2016 Aug 26.

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences Tehran, Iran.

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http://dx.doi.org/10.3389/fphys.2016.00375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999434PMC
September 2016

Cancerome: A hidden informative subnetwork of the diseasome.

Comput Biol Med 2016 09 20;76:173-7. Epub 2016 Jul 20.

Hematology, Oncology and SCT Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Neoplastic disorders are a leading cause of mortality and morbidity worldwide. Studying the relationships between different cancers using high throughput-generated data may elucidate undisclosed aspects of cancer etiology, diagnosis, and treatment. Several studies have described relationships between different diseases based on genes, proteins, pathways, gene ontology, comorbidity, symptoms, and other features. In this study, we first constructed an integrated human disease network based on nine different biological aspects, including molecular, functional, and clinical features. Next, we extracted the cancerome as a cancer-related subnetwork. Further investigation of cancerome could reveal hidden mechanisms of cancer and could be useful in developing new diagnostic tests and effective new drugs.
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http://dx.doi.org/10.1016/j.compbiomed.2016.07.010DOI Listing
September 2016

Functional Brain Networks: Does the Choice of Dependency Estimator and Binarization Method Matter?

Authors:
Mahdi Jalili

Sci Rep 2016 07 15;6:29780. Epub 2016 Jul 15.

School of Engineering, RMIT University, Melbourne, Australia.

The human brain can be modelled as a complex networked structure with brain regions as individual nodes and their anatomical/functional links as edges. Functional brain networks are constructed by first extracting weighted connectivity matrices, and then binarizing them to minimize the noise level. Different methods have been used to estimate the dependency values between the nodes and to obtain a binary network from a weighted connectivity matrix. In this work we study topological properties of EEG-based functional networks in Alzheimer's Disease (AD). To estimate the connectivity strength between two time series, we use Pearson correlation, coherence, phase order parameter and synchronization likelihood. In order to binarize the weighted connectivity matrices, we use Minimum Spanning Tree (MST), Minimum Connected Component (MCC), uniform threshold and density-preserving methods. We find that the detected AD-related abnormalities highly depend on the methods used for dependency estimation and binarization. Topological properties of networks constructed using coherence method and MCC binarization show more significant differences between AD and healthy subjects than the other methods. These results might explain contradictory results reported in the literature for network properties specific to AD symptoms. The analysis method should be seriously taken into account in the interpretation of network-based analysis of brain signals.
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http://dx.doi.org/10.1038/srep29780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945914PMC
July 2016

Directed Functional Networks in Alzheimer's Disease: Disruption of Global and Local Connectivity Measures.

IEEE J Biomed Health Inform 2017 07 9;21(4):949-955. Epub 2016 Jun 9.

Techniques available in graph theory can be applied to signals recorded from human brain. In network analysis of EEG signals, the individual nodes are EEG sensor locations and the edges correspond to functional relations between them that are extracted from EEG time series. In this paper, we study EEG-based directed functional networks in Alzheimer's disease (AD). To this end, directed connectivity matrices of 25 AD patients and 26 healthy subjects are processed and a number of meaningful graph theory metrics are studied. Our data show that functional networks of AD brains have significantly reduced global connectivity in alpha and beta bands (P < 0.05). The AD brains have significantly higher local connectivity than healthy controls in alpha and beta bands. This decreased profile in global connectivity can be linked to compensatory increased local connectivity as a result of wide-spread decline in the long-range connections. We also study resiliency of brain networks against targeted attack to hub nodes and find that AD networks are less resilient than healthy brains in alpha and beta bands.
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http://dx.doi.org/10.1109/JBHI.2016.2578954DOI Listing
July 2017