Journal of Computational Biology最新文献

{"title":"Positivity and Boundedness Preserving Numerical Scheme for a Stochastic Multigroup Susceptible-Infected-Recovering Epidemic Model with Age Structure.","authors":"Han Ma, Yanyan Du, Zong Wang, Qimin Zhang","doi":"10.1089/cmb.2023.0443","DOIUrl":"10.1089/cmb.2023.0443","url":null,"abstract":"<p><p>Since the stochastic age-structured multigroup susceptible-infected-recovering (SIR) epidemic model is nonlinear, the solution of this model is hard to be explicitly represented. It is necessary to construct effective numerical methods so as to predict the number of infections. In addition, the stochastic age-structured multigroup SIR model has features of positivity and boundedness of the solution. Therefore, in this article, in order to ensure that the numerical and analytical solutions must have the same properties, by modifying the classical Euler-Maruyama (EM) scheme, we generate a positivity and boundedness preserving EM (PBPEM) method on temporal space for stochastic age-structured multigroup SIR model, which is proved to have a strong convergence to the true solution over finite time intervals. Moreover, by combining the standard finite element method and the PBPEM method, we propose a full-discrete scheme to show the numerical solutions, as well as analyze the error estimations. Finally, the full-discrete scheme is applied to a general stochastic two-group SIR model and the Chlamydia epidemic model, which shows the superiority of the numerical method.</p>","PeriodicalId":15526,"journal":{"name":"Journal of Computational Biology","volume":" ","pages":"1259-1290"},"PeriodicalIF":1.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Policy to Prediction: Assessing Forecasting Accuracy in an Integrated Framework with Machine Learning and Disease Models.","authors":"Amit K Chakraborty, Hao Wang, Pouria Ramazi","doi":"10.1089/cmb.2023.0377","DOIUrl":"10.1089/cmb.2023.0377","url":null,"abstract":"<p><p>To improve the forecasting accuracy of the spread of infectious diseases, a hybrid model was recently introduced where the commonly assumed constant disease transmission rate was actively estimated from enforced mitigating policy data by a machine learning (ML) model and then fed to an extended susceptible-infected-recovered model to forecast the number of infected cases. Testing only one ML model, that is, gradient boosting model (GBM), the work left open whether other ML models would perform better. Here, we compared GBMs, linear regressions, k-nearest neighbors, and Bayesian networks (BNs) in forecasting the number of COVID-19-infected cases in the United States and Canadian provinces based on policy indices of future 35 days. There was no significant difference in the mean absolute percentage errors of these ML models over the combined dataset [<math><mrow><mi>H</mi><mo>(</mo><mn>3</mn><mo>)</mo><mo>=</mo><mn>3.10</mn><mo>,</mo><mi>p</mi><mo>=</mo><mn>0.38</mn></mrow></math>]. In two provinces, a significant difference was observed [<math><mrow><mi>H</mi><mo>(</mo><mn>3</mn><mo>)</mo><mo>=</mo><mn>8.77</mn><mo>,</mo><mi>H</mi><mo>(</mo><mn>3</mn><mo>)</mo><mo>=</mo><mn>8.07</mn><mo>,</mo><mi>p</mi><mo><</mo><mn>0.05</mn></mrow></math>], yet posthoc tests revealed no significant difference in pairwise comparisons. Nevertheless, BNs significantly outperformed the other models in most of the training datasets. The results put forward that the ML models have equal forecasting power overall, and BNs are best for data-fitting applications.</p>","PeriodicalId":15526,"journal":{"name":"Journal of Computational Biology","volume":" ","pages":"1104-1117"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Noise to Knowledge: Diffusion Probabilistic Model-Based Neural Inference of Gene Regulatory Networks.","authors":"Hao Zhu, Donna Slonim","doi":"10.1089/cmb.2024.0607","DOIUrl":"10.1089/cmb.2024.0607","url":null,"abstract":"<p><p>Understanding gene regulatory networks (GRNs) is crucial for elucidating cellular mechanisms and advancing therapeutic interventions. Original methods for GRN inference from bulk expression data often struggled with the high dimensionality and inherent noise in the data. Here we introduce RegDiffusion, a new class of Denoising Diffusion Probabilistic Models focusing on the regulatory effects among feature variables. RegDiffusion introduces Gaussian noise to the input data following a diffusion schedule and uses a neural network with a parameterized adjacency matrix to predict the added noise. We show that using this process, GRNs can be learned effectively with a surprisingly simple model architecture. In our benchmark experiments, RegDiffusion shows superior performance compared to several baseline methods in multiple datasets. We also demonstrate that RegDiffusion can infer biologically meaningful regulatory networks from real-world single-cell data sets with over 15,000 genes in under 5 minutes. This work not only introduces a fresh perspective on GRN inference but also highlights the promising capacity of diffusion-based models in the area of single-cell analysis. The RegDiffusion software package and experiment data are available at https://github.com/TuftsBCB/RegDiffusion.</p>","PeriodicalId":15526,"journal":{"name":"Journal of Computational Biology","volume":" ","pages":"1087-1103"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network-Constrained Eigen-Single-Cell Profile Estimation for Uncovering Crucial Immunogene Regulatory Systems in Human Bone Marrow.","authors":"Heewon Park, Satoru Miyano","doi":"10.1089/cmb.2024.0539","DOIUrl":"10.1089/cmb.2024.0539","url":null,"abstract":"<p><p>We focus on characterizing cell lines from young and aged-healthy and -AML (acute myeloid leukemia) cell lines, and our goal is to identify the key markers associated with the progression of AML. To characterize the age-related phenotypes in AML cell lines, we consider eigenCell analysis that effectively encapsulates the primary expression level patterns across the cell lines. However, earlier investigations utilizing eigenGenes and eigenCells analysis were based on linear combination of all features, leading to the disturbance from noise features. Moreover, the analysis based on a fully dense loading matrix makes it challenging to interpret the results of eigenCells analysis. In order to address these challenges, we develop a novel computational approach termed network-constrained eigenCells profile estimation, which employs a sparse learning strategy. The proposed method estimates eigenCell based on not only the lasso but also network constrained penalization. The use of the network-constrained penalization enables us to simultaneously select neighborhood genes. Furthermore, the hub genes and their regulator/target genes are easily selected as crucial markers for eigenCells estimation. That is, our method can incorporate insights from network biology into the process of sparse loading estimation. Through our methodology, we estimate sparse eigenCells profiles, where only critical markers exhibit expression levels. This allows us to identify the key markers associated with a specific phenotype. Monte Carlo simulations demonstrate the efficacy of our method in reconstructing the sparse structure of eigenCells profiles. We employed our approach to unveil the regulatory system of immunogenes in both young/aged-healthy and -AML cell lines. The markers we have identified for the age-related phenotype in both healthy and AML cell lines have garnered strong support from previous studies. Specifically, our findings, in conjunction with the existing literature, indicate that the activities within this subnetwork of CD79A could be pivotal in elucidating the mechanism driving AML progression, particularly noting the significant role played by the diminished activities in the CD79A subnetwork. We expect that the proposed method will be a useful tool for characterizing disease-related subsets of cell lines, encompassing phenotypes and clones.</p>","PeriodicalId":15526,"journal":{"name":"Journal of Computational Biology","volume":" ","pages":"1158-1178"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Hybrid GNN Approach for Improved Molecular Property Prediction.","authors":"Pedro Quesado, Luis H M Torres, Bernardete Ribeiro, Joel P Arrais","doi":"10.1089/cmb.2023.0452","DOIUrl":"10.1089/cmb.2023.0452","url":null,"abstract":"<p><p>The development of new drugs is a vital effort that has the potential to improve human health, well-being and life expectancy. Molecular property prediction is a crucial step in drug discovery, as it helps to identify potential therapeutic compounds. However, experimental methods for drug development can often be time-consuming and resource-intensive, with a low probability of success. To address such limitations, deep learning (DL) methods have emerged as a viable alternative due to their ability to identify high-discriminating patterns in molecular data. In particular, graph neural networks (GNNs) operate on graph-structured data to identify promising drug candidates with desirable molecular properties. These methods represent molecules as a set of node (atoms) and edge (chemical bonds) features to aggregate local information for molecular graph representation learning. Despite the availability of several GNN frameworks, each approach has its own shortcomings. Although, some GNNs may excel in certain tasks, they may not perform as well in others. In this work, we propose a hybrid approach that incorporates different graph-based methods to combine their strengths and mitigate their limitations to accurately predict molecular properties. The proposed approach consists in a multi-layered hybrid GNN architecture that integrates multiple GNN frameworks to compute graph embeddings for molecular property prediction. Furthermore, we conduct extensive experiments on multiple benchmark datasets to demonstrate that our hybrid approach significantly outperforms the state-of-the-art graph-based models. The data and code scripts to reproduce the results are available in the repository, https://github.com/pedro-quesado/HybridGNN.</p>","PeriodicalId":15526,"journal":{"name":"Journal of Computational Biology","volume":" ","pages":"1146-1157"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correcting for Observation Bias in Cancer Progression Modeling.","authors":"Rudolf Schill, Maren Klever, Andreas Lösch, Y Linda Hu, Stefan Vocht, Kevin Rupp, Lars Grasedyck, Rainer Spang, Niko Beerenwinkel","doi":"10.1089/cmb.2024.0666","DOIUrl":"10.1089/cmb.2024.0666","url":null,"abstract":"<p><p>Tumor progression is driven by the accumulation of genetic alterations, including both point mutations and copy number changes. Understanding the temporal sequence of these events is crucial for comprehending the disease but is not directly discernible from cross-sectional genomic data. Cancer progression models, including Mutual Hazard Networks (MHNs), aim to reconstruct the dynamics of tumor progression by learning the causal interactions between genetic events based on their co-occurrence patterns in cross-sectional data. Here, we highlight a commonly overlooked bias in cross-sectional datasets that can distort progression modeling. Tumors become clinically detectable when they cause symptoms or are identified through imaging or tests. Detection factors, such as size, inflammation (fever, fatigue), and elevated biochemical markers, are influenced by genomic alterations. Ignoring these effects leads to \"conditioning on a collider\" bias, where events making the tumor more observable appear anticorrelated, creating false suppressive effects or masking promoting effects among genetic events. We enhance MHNs by incorporating the effects of genetic progression events on the inclusion of a tumor in a dataset, thus correcting for collider bias. We derive an efficient tensor formula for the likelihood function and apply it to two datasets from the MSK-IMPACT study. In colon adenocarcinoma, we observe a significantly higher rate of clinical detection for TP53-positive tumors, while in lung adenocarcinoma, the same is true for EGFR-positive tumors. Compared to classical MHNs, this approach eliminates several spurious suppressive interactions and uncovers multiple promoting effects.</p>","PeriodicalId":15526,"journal":{"name":"Journal of Computational Biology","volume":"31 10","pages":"927-945"},"PeriodicalIF":1.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RECOMB 2024 Special Issue.","authors":"Jian Ma, Mona Singh","doi":"10.1089/cmb.2024.0809","DOIUrl":"10.1089/cmb.2024.0809","url":null,"abstract":"","PeriodicalId":15526,"journal":{"name":"Journal of Computational Biology","volume":" ","pages":"907"},"PeriodicalIF":1.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approximate IsoRank for Scalable and Functionally Meaningful Cross-Species Alignments of Protein Interaction Networks.","authors":"Kapil Devkota, Anselm Blumer, Xiaozhe Hu, Lenore Cowen","doi":"10.1089/cmb.2024.0673","DOIUrl":"10.1089/cmb.2024.0673","url":null,"abstract":"<p><p>The IsoRank algorithm of Singh, Xu, and Berger was a pioneering algorithmic advance that applied spectral methods to the problem of cross-species global alignment of biological networks. We develop a new IsoRank approximation that exploits the mathematical properties of IsoRank's linear system to solve the problem in quadratic time with respect to the maximum size of the two protein-protein interaction (PPI) networks. We further propose a refinement to this initial approximation so that the updated result is even closer to the original IsoRank formulation while remaining computationally inexpensive. In experiments on synthetic and real PPI networks with various proposed metrics to measure alignment quality, we find the results of our approximate IsoRank are nearly as accurate as the original IsoRank. In fact, for functional enrichment-based measures of global network alignment quality, our approximation performs better than the exact IsoRank, which is doubtless because it is more robust to the noise of missing or incorrect edges. It also performs competitively against two more recent global network alignment algorithms. We also present an analogous approximation to IsoRankN, which extends the network alignment to more than two species.</p>","PeriodicalId":15526,"journal":{"name":"Journal of Computational Biology","volume":" ","pages":"990-1007"},"PeriodicalIF":1.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust Optimal Metabolic Factories.","authors":"Spencer Krieger, John Kececioglu","doi":"10.1089/cmb.2024.0748","DOIUrl":"10.1089/cmb.2024.0748","url":null,"abstract":"<p><p>Perhaps the most fundamental model in synthetic and systems biology for inferring pathways in metabolic reaction networks is a metabolic <i>factory</i>: a system of reactions that starts from a set of source compounds and produces a set of target molecules, while conserving or not depleting intermediate metabolites. Finding a shortest factory-that minimizes a sum of real-valued weights on its reactions to infer the most likely pathway-is NP-complete. The current state-of-the-art for shortest factories solves a mixed-integer linear program with a major drawback: it requires the user to set a critical parameter, where too large a value can make optimal solutions infeasible, while too small a value can yield degenerate solutions due to numerical error. We present the first <i>robust algorithm</i> for optimal factories that is both <i>parameter-free</i> (relieving the user from determining a parameter setting) and <i>degeneracy-free</i> (guaranteeing it finds an optimal nondegenerate solution). We also give for the first time a <i>complete characterization</i> of the graph-theoretic structure of shortest factories, that reveals an important class of degenerate solutions which was overlooked and potentially output by the prior state-of-the-art.We show degeneracy is precisely due to <i>invalid stoichiometries</i> in reactions, and provide an efficient algorithm for identifying all such <i>misannotations</i> in a metabolic network. In addition we settle the relationship between the two established pathway models of <i>hyperpaths</i> and factories by proving hyperpaths actually comprise a <i>subclass</i> of factories. Comprehensive experiments over all instances from the standard metabolic reaction databases in the literature demonstrate our parameter-free exact algorithm is <i>fast in practice</i>, quickly finding optimal factories in large real-world networks containing thousands of reactions. A preliminary implementation of our robust algorithm for shortest factories in a new tool called Freeia is available free for research use at http://freeia.cs.arizona.edu.</p>","PeriodicalId":15526,"journal":{"name":"Journal of Computational Biology","volume":" ","pages":"1045-1086"},"PeriodicalIF":1.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lossless Approximate Pattern Matching: Automated Design of Efficient Search Schemes.","authors":"Luca Renders, Lore Depuydt, Sven Rahmann, Jan Fostier","doi":"10.1089/cmb.2024.0664","DOIUrl":"10.1089/cmb.2024.0664","url":null,"abstract":"<p><p>This study introduces a pioneering approach to automate the creation of search schemes for lossless approximate pattern matching. Search schemes are combinatorial structures that define a series of searches over a partitioned pattern. Each search specifies the processing order of these parts and the cumulative lower and upper bounds on the number of errors in each part of the pattern. Together, these searches ensure the identification of all approximate occurrences of a search pattern within a predefined limit of <i>k</i> errors. While existing literature offers designed schemes for up to <i>k</i> = 4 errors, designing search schemes for larger <i>k</i> values incurs escalating computational costs. Our method integrates a greedy algorithm and a novel Integer Linear Programming (ILP) formulation to design efficient search schemes for up to <i>k</i> = 7 errors. Comparative analyses demonstrate the superiority of our ILP-optimal schemes over alternative strategies in both theoretical and practical contexts. Additionally, we propose a dynamic scheme selection technique tailored to specific search patterns, further enhancing efficiency. Combined, this yields runtime reductions of up to 53% for higher <i>k</i> values. To facilitate search scheme generation, we present Hato, an open-source software tool (AGPL-3.0 license) employing the greedy algorithm and utilizing CPLEX for ILP solving. Furthermore, we introduce Columba 1.2, an open-source lossless read-mapper (AGPL-3.0 license) implemented in C++. Columba surpasses existing state-of-the-art tools by identifying all approximate occurrences of 100,000 Illumina reads (150 bp) in the human reference genome within 24 seconds (maximum edit distance of 4) and 75 seconds (maximum edit distance of 6) using a single CPU core. Notably, our study showcases Columba's capability to align 100,000 reads of length 50, with high error rates and up to an edit distance of 7, in a mere 2 hours and 15 minutes. This achievement is unmatched by other lossless aligners, which require over 3 hours for edit distance 5 alignments. Moreover, Columba exhibits a mapping rate four times higher than that of a lossy tool for this dataset.</p>","PeriodicalId":15526,"journal":{"name":"Journal of Computational Biology","volume":" ","pages":"975-989"},"PeriodicalIF":1.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}