An Integer Programming Formulation of the Minimum Common String Partition Problem.
Ontology highlight
ABSTRACT:
SUBMITTER: Ferdous SM
PROVIDER: S-EPMC4489654 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
An Integer Programming Formulation of the Minimum Common String Partition Problem.
Ferdous S M SM Rahman M Sohel MS
PloS one 20150702 7
We consider the problem of finding a minimum common string partition (MCSP) of two strings, which is an NP-hard problem. The MCSP problem is closely related to genome comparison and rearrangement, an important field in Computational Biology. In this paper, we map the MCSP problem into a graph applying a prior technique and using this graph, we develop an Integer Linear Programming (ILP) formulation for the problem. We implement the ILP formulation and compare the results with the state-of-the-ar ...[more]
Similar Datasets
Project description:Understanding the mechanisms of cell function and drug action is a major endeavor in the pharmaceutical industry. Drug effects are governed by the intrinsic properties of the drug (i.e., selectivity and potency) and the specific signaling transduction network of the host (i.e., normal vs. diseased cells). Here, we describe an unbiased, phosphoproteomic-based approach to identify drug effects by monitoring drug-induced topology alterations. With our proposed method, drug effects are investigated under diverse stimulations of the signaling network. Starting with a generic pathway made of logical gates, we build a cell-type specific map by constraining it to fit 13 key phopshoprotein signals under 55 experimental conditions. Fitting is performed via an Integer Linear Program (ILP) formulation and solution by standard ILP solvers; a procedure that drastically outperforms previous fitting schemes. Then, knowing the cell's topology, we monitor the same key phosphoprotein signals under the presence of drug and we re-optimize the specific map to reveal drug-induced topology alterations. To prove our case, we make a topology for the hepatocytic cell-line HepG2 and we evaluate the effects of 4 drugs: 3 selective inhibitors for the Epidermal Growth Factor Receptor (EGFR) and a non-selective drug. We confirm effects easily predictable from the drugs' main target (i.e., EGFR inhibitors blocks the EGFR pathway) but we also uncover unanticipated effects due to either drug promiscuity or the cell's specific topology. An interesting finding is that the selective EGFR inhibitor Gefitinib inhibits signaling downstream the Interleukin-1alpha (IL1alpha) pathway; an effect that cannot be extracted from binding affinity-based approaches. Our method represents an unbiased approach to identify drug effects on small to medium size pathways which is scalable to larger topologies with any type of signaling interventions (small molecules, RNAi, etc). The method can reveal drug effects on pathways, the cornerstone for identifying mechanisms of drug's efficacy.
| S-EPMC2776985 | biostudies-literature
Project description:MotivationPrimary purpose of modeling gene regulatory networks for developmental process is to reveal pathways governing the cellular differentiation to specific phenotypes. Knowledge of differentiation network will enable generation of desired cell fates by careful alteration of the governing network by adequate manipulation of cellular environment.ResultsWe have developed a novel integer programming-based approach to reconstruct the underlying regulatory architecture of differentiating embryonic stem cells from discrete temporal gene expression data. The network reconstruction problem is formulated using inherent features of biological networks: (i) that of cascade architecture which enables treatment of the entire complex network as a set of interconnected modules and (ii) that of sparsity of interconnection between the transcription factors. The developed framework is applied to the system of embryonic stem cells differentiating towards pancreatic lineage. Experimentally determined expression profile dynamics of relevant transcription factors serve as the input to the network identification algorithm. The developed formulation accurately captures many of the known regulatory modes involved in pancreatic differentiation. The predictive capacity of the model is tested by simulating an in silico potential pathway of subsequent differentiation. The predicted pathway is experimentally verified by concurrent differentiation experiments. Experimental results agree well with model predictions, thereby illustrating the predictive accuracy of the proposed algorithm.Contactipb1@pitt.eduSupplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC2865861 | biostudies-literature
Project description:MotivationSignal-transduction networks are often aberrated in cancer cells, and new anti-cancer drugs that specifically target oncogenes involved in signaling show great clinical promise. However, the effectiveness of such targeted treatments is often hampered by innate or acquired resistance due to feedbacks, crosstalks or network adaptations in response to drug treatment. A quantitative understanding of these signaling networks and how they differ between cells with different oncogenic mutations or between sensitive and resistant cells can help in addressing this problem.ResultsHere, we present Comparative Network Reconstruction (CNR), a computational method to reconstruct signaling networks based on possibly incomplete perturbation data, and to identify which edges differ quantitatively between two or more signaling networks. Prior knowledge about network topology is not required but can straightforwardly be incorporated. We extensively tested our approach using simulated data and applied it to perturbation data from a BRAF mutant, PTPN11 KO cell line that developed resistance to BRAF inhibition. Comparing the reconstructed networks of sensitive and resistant cells suggests that the resistance mechanism involves re-establishing wild-type MAPK signaling, possibly through an alternative RAF-isoform.Availability and implementationCNR is available as a python module at https://github.com/NKI-CCB/cnr. Additionally, code to reproduce all figures is available at https://github.com/NKI-CCB/CNR-analyses.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC6129277 | biostudies-literature
Project description:Subspecies nomenclature systems of pathogens are increasingly based on sequence data. The use of phylogenetics to identify and differentiate between clusters of genetically similar pathogens is particularly prevalent in virology from the nomenclature of human papillomaviruses to highly pathogenic avian influenza (HPAI) H5Nx viruses. These nomenclature systems rely on absolute genetic distance thresholds to define the maximum genetic divergence tolerated between viruses designated as closely related. However, the phylogenetic clustering methods used in these nomenclature systems are limited by the arbitrariness of setting intra and intercluster diversity thresholds. The lack of a consensus ground truth to define well-delineated, meaningful phylogenetic subpopulations amplifies the difficulties in identifying an informative distance threshold. Consequently, phylogenetic clustering often becomes an exploratory, ad hoc exercise. Phylogenetic Clustering by Linear Integer Programming (PhyCLIP) was developed to provide a statistically principled phylogenetic clustering framework that negates the need for an arbitrarily defined distance threshold. Using the pairwise patristic distance distributions of an input phylogeny, PhyCLIP parameterizes the intra and intercluster divergence limits as statistical bounds in an integer linear programming model which is subsequently optimized to cluster as many sequences as possible. When applied to the hemagglutinin phylogeny of HPAI H5Nx viruses, PhyCLIP was not only able to recapitulate the current WHO/OIE/FAO H5 nomenclature system but also further delineated informative higher resolution clusters that capture geographically distinct subpopulations of viruses. PhyCLIP is pathogen-agnostic and can be generalized to a wide variety of research questions concerning the identification of biologically informative clusters in pathogen phylogenies. PhyCLIP is freely available at http://github.com/alvinxhan/PhyCLIP, last accessed March 15, 2019.
| S-EPMC6573476 | biostudies-literature
Project description:Background and purposePatients received by radiotherapy departments are diverse and may be diagnosed with different cancers. Therefore, they need different radiotherapy treatment plans and thus have different needs for medical resources. This research aims to explore the best method of scheduling the admission of patients receiving radiotherapy so as to reduce patient loss and maximize the usage efficiency of service resources.Materials and methodsA mix integer programming (MIP) model integrated with special features of radiotherapy is constructed. The data used here is based on the historical data collected and we propose an exact method to solve the MIP model.ResultsCompared with the traditional First Come First Served (FCFS) method, the new method has boosted patient admission as well as the usage of linear accelerators (LINAC) and beds.ConclusionsThe integer programming model can be used to describe the complex problem of scheduling radio-receiving patients, to identify the bottleneck resources that hinder patient admission, and to obtain the optimal LINAC-bed radio under the current data conditions. Different management strategies can be implemented by adjusting the settings of the MIP model. The computational results can serve as a reference for the policy-makers in decision making.
| S-EPMC5503264 | biostudies-literature
Project description:Biogeography-based optimization (BBO) is a relatively new bioinspired heuristic for global optimization based on the mathematical models of biogeography. By investigating the applicability and performance of BBO for integer programming, we find that the original BBO algorithm does not perform well on a set of benchmark integer programming problems. Thus we modify the mutation operator and/or the neighborhood structure of the algorithm, resulting in three new BBO-based methods, named BlendBBO, BBO_DE, and LBBO_LDE, respectively. Computational experiments show that these methods are competitive approaches to solve integer programming problems, and the LBBO_LDE shows the best performance on the benchmark problems.
| S-EPMC4065689 | biostudies-other
Project description:MotivationCombinatorial therapies play increasingly important roles in combating complex diseases. Owing to the huge cost associated with experimental methods in identifying optimal drug combinations, computational approaches can provide a guide to limit the search space and reduce cost. However, few computational approaches have been developed for this purpose, and thus there is a great need of new algorithms for drug combination prediction.ResultsHere we proposed to formulate the optimal combinatorial therapy problem into two complementary mathematical algorithms, Balanced Target Set Cover (BTSC) and Minimum Off-Target Set Cover (MOTSC). Given a disease gene set, BTSC seeks a balanced solution that maximizes the coverage on the disease genes and minimizes the off-target hits at the same time. MOTSC seeks a full coverage on the disease gene set while minimizing the off-target set. Through simulation, both BTSC and MOTSC demonstrated a much faster running time over exhaustive search with the same accuracy. When applied to real disease gene sets, our algorithms not only identified known drug combinations, but also predicted novel drug combinations that are worth further testing. In addition, we developed a web-based tool to allow users to iteratively search for optimal drug combinations given a user-defined gene set.AvailabilityOur tool is freely available for noncommercial use at http://www.drug.liuzlab.org/.Contactzhandong.liu@bcm.eduSupplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC4016706 | biostudies-literature
Project description:A gene is considered as essential when it is indispensable for cells to grow and replicate in a certain environment. However, gene essentiality is not a structural property but rather a contextual one, which depends on the specific biological conditions affecting the cell. This circumstantial essentiality of genes is what brings the attention of scientist since we can identify genes essential for cancer cells but not essential for healthy cells. This same contextuality makes their identification extremely challenging. Huge experimental efforts such as Project Achilles where the essentiality of thousands of genes is measured together with a plethora of molecular data (transcriptomics, copy number, mutations, etc.) in over one thousand cell lines can shed light on the causality behind the essentiality of a gene in a given environment. Here, we present an in-silico method for the identification of patient-specific essential genes using constraint-based modelling (CBM). Our method expands the ideas behind traditional CBM to accommodate multisystem networks. In essence, it first calculates the minimum number of lowly expressed genes required to be activated by the cell to sustain life as defined by a set of requirements; and second, it performs an exhaustive in-silico gene knockout to find those that lead to the need of activating additional lowly expressed genes. We validated the proposed methodology using a set of 452 cancer cell lines derived from the Cancer Cell Line Encyclopedia where an exhaustive experimental large-scale gene knockout study using CRISPR (Achilles Project) evaluates the impact of each removal. We also show that the integration of different essentiality predictions per gene, what we called Essentiality Congruity Score, reduces the number of false positives. Finally, we explored our method in a breast cancer patient dataset, and our results showed high concordance with previous publications. These findings suggest that identifying genes whose activity is fundamental to sustain cellular life in a patient-specific manner is feasible using in-silico methods. The patient-level gene essentiality predictions can pave the way for precision medicine by identifying potential drug targets whose deletion can induce death in tumour cells.
| S-EPMC9357337 | biostudies-literature
Project description:Automatically generating a summary for asynchronous data can help users to keep up with the rapid growth of multi-modal information on the Internet. However, the current multi-modal systems usually generate summaries composed of text and images. In this paper, we propose a novel research problem of text-image-video summary generation (TIVS). We first develop a multi-modal dataset containing text documents, images and videos. We then propose a novel joint integer linear programming multi-modal summarization (JILP-MMS) framework. We report the performance of our model on the developed dataset.
| S-EPMC7148046 | biostudies-literature
Project description:Phylogenetic diversity (PD) is a measure of biodiversity based on the evolutionary history of species. Here, we discuss several optimization problems related to the use of PD, and the more general measure split diversity (SD), in conservation prioritization.Depending on the conservation goal and the information available about species, one can construct optimization routines that incorporate various conservation constraints. We demonstrate how this information can be used to select sets of species for conservation action. Specifically, we discuss the use of species' geographic distributions, the choice of candidates under economic pressure, and the use of predator-prey interactions between the species in a community to define viability constraints.Despite such optimization problems falling into the area of NP hard problems, it is possible to solve them in a reasonable amount of time using integer programming. We apply integer linear programming to a variety of models for conservation prioritization that incorporate the SD measure.We exemplarily show the results for two data sets: the Cape region of South Africa and a Caribbean coral reef community. Finally, we provide user-friendly software at http://www.cibiv.at/software/pda.
| S-EPMC4392707 | biostudies-literature