Interdisciplinary Sciences: Computational Life Sciences最新文献

{"title":"Predicting Synergistic Drug Combinations Based on Fusion of Cell and Drug Molecular Structures.","authors":"Shiyu Yan, Gang Yu, Jiaoxing Yang, Lingna Chen","doi":"10.1007/s12539-025-00695-6","DOIUrl":"https://doi.org/10.1007/s12539-025-00695-6","url":null,"abstract":"<p><p>Drug combination therapy has shown improved efficacy and decreased adverse effects, making it a practical approach for conditions like cancer. However, discovering all potential synergistic drug combinations requires extensive experimentation, which can be challenging. Recent research utilizing deep learning techniques has shown promise in reducing the number of experiments and overall workload by predicting synergistic drug combinations. Therefore, developing reliable and effective computational methods for predicting these combinations is essential. This paper proposed a novel method called Drug-molecule Connect Cell (DconnC) for predicting synergistic drug combinations. DconnC leverages cellular features as nodes to establish connections between drug molecular structures, allowing the extraction of pertinent features. These features are then optimized through self-augmented contrastive learning using bidirectional recurrent neural networks (Bi-RNN) and long short-term memory (LSTM) models, ultimately predicting the drug synergy. By integrating information about the molecular structure of drugs for the extraction of cell features, DconnC uncovers the inherent connection between drug molecular structures and cellular characteristics, thus improving the accuracy of predictions. The performance of our method is evaluated using a five-fold cross validation approach, demonstrating a 35 <math><mo>%</mo></math> reduction in the mean square error (MSE) compared to the next-best method. Moreover, our method significantly outperformed alternative approaches in various evaluation criteria, particularly in predicting different cell lines and Loewe synergy score intervals.</p>","PeriodicalId":13670,"journal":{"name":"Interdisciplinary Sciences: Computational Life Sciences","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing the Accuracy of Anti-MRSA Peptide Prediction Through Integrating Multi-Source Protein Language Models.","authors":"Watshara Shoombuatong, Pakpoom Mookdarsanit, Lawankorn Mookdarsanit, Nalini Schaduangrat, Saeed Ahmed, Muhammad Kabir, Pramote Chumnanpuen","doi":"10.1007/s12539-025-00696-5","DOIUrl":"https://doi.org/10.1007/s12539-025-00696-5","url":null,"abstract":"<p><p>The emergence of methicillin-resistant Staphylococcus aureus (MRSA) as a recognized cause of community-acquired and hospital infections has brought about a need for the efficient and accurate identification of peptides with anti-MRSA properties in drug discovery and development pipelines. However, current experimental methods often tend to be labor- and resource-intensive. Thus, there is an immediate requirement to develop practical computational solutions for identifying sequence-based anti-MRSA peptides. Lately, pre-trained protein language models (pLMs) have emerged as a remarkable advancement for encoding peptide sequences as discriminative feature embeddings, uncovering plentiful protein-level information and successfully repurposing it for in silico peptide property prediction. In this study, we present pLM4MRSA, a framework based on pLMs designed to enhance the accuracy of predicting anti-MRSA peptides. In this framework, we combine feature embeddings from various pLMs, such as ProtTrans, and evolutionary-scale modeling (ESM-2) which provide complementary information for prediction. These individual pLM strengths are integrated to form hybrid feature embeddings. Next, we apply principal component analysis (PCA) to process these hybrid embeddings. The resulting PCA-transformed feature vectors are then used as inputs for constructing the predictive model. Experimental results on the independent test dataset showed that the proposed pLM4MRSA approach achieved a balanced accuracy and Matthew correlation coefficient of 0.983 and 0.980, respectively, representing remarkable improvements over the state-of-the-art methods by 2.53%-4.83% and 7.73%-13.23%, respectively. This indicates that pLM4MRSA is a high-performance prediction model with excellent scope of applicability. Additionally, comparison with well-known hand-crafted features demonstrated that the proposed hybrid feature embeddings complement each other effectively, capturing discriminative patterns for more accurate anti-MRSA peptide prediction. We anticipate that pLM4MRSA will serve as an effective solution for accurate and high-capacity prediction of anti-MRSA peptides from peptide sequences.</p>","PeriodicalId":13670,"journal":{"name":"Interdisciplinary Sciences: Computational Life Sciences","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reinforced Collaborative-Competitive Representation for Biomedical Image Recognition.","authors":"Junwei Jin, Songbo Zhou, Yanting Li, Tanxin Zhu, Chao Fan, Hua Zhang, Peng Li","doi":"10.1007/s12539-024-00683-2","DOIUrl":"10.1007/s12539-024-00683-2","url":null,"abstract":"<p><p>Artificial intelligence technology has demonstrated remarkable diagnostic efficacy in modern biomedical image analysis. However, the practical application of artificial intelligence is significantly limited by the presence of similar pathologies among different diseases and the diversity of pathologies within the same disease. To address this issue, this paper proposes a reinforced collaborative-competitive representation classification (RCCRC) method. RCCRC enhances the contribution of different classes by introducing dual competitive constraints into the objective function. The first constraint integrates the collaborative space representation akin to holistic data, promoting the representation contribution of similar classes. The second constraint introduces specific class subspace representations to encourage competition among all classes, enhancing the discriminative nature of representation vectors. By unifying these two constraints, RCCRC effectively explores both global and specific data features in the reconstruction space. Extensive experiments on various biomedical image databases are conducted to exhibit the advantage of the proposed method in comparison with several state-of-the-art classification algorithms.</p>","PeriodicalId":13670,"journal":{"name":"Interdisciplinary Sciences: Computational Life Sciences","volume":" ","pages":"215-230"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"misORFPred: A Novel Method to Mine Translatable sORFs in Plant Pri-miRNAs Using Enhanced Scalable k-mer and Dynamic Ensemble Voting Strategy.","authors":"Haibin Li, Jun Meng, Zhaowei Wang, Yushi Luan","doi":"10.1007/s12539-024-00661-8","DOIUrl":"10.1007/s12539-024-00661-8","url":null,"abstract":"<p><p>The primary microRNAs (pri-miRNAs) have been observed to contain translatable small open reading frames (sORFs) that can encode peptides as an independent element. Relevant studies have proven that those of sORFs are of significance in regulating the expression of biological traits. The existing methods for predicting the coding potential of sORFs frequently overlook this data or categorize them as negative samples, impeding the identification of additional translatable sORFs in pri-miRNAs. In light of this, a novel method named misORFPred has been proposed. Specifically, an enhanced scalable k-mer (ESKmer) that simultaneously integrates the composition information within a sequence and distance information between sequences is designed to extract the nucleotide sequence features. After feature selection, the optimal features and several machine learning classifiers are combined to construct the ensemble model, where a newly devised dynamic ensemble voting strategy (DEVS) is proposed to dynamically adjust the weights of base classifiers and adaptively select the optimal base classifiers for each unlabeled sample. Cross-validation results suggest that ESKmer and DEVS are essential for this classification task and could boost model performance. Independent testing results indicate that misORFPred outperforms the state-of-the-art methods. Furthermore, we execute misORFPerd on the genomes of various plant species and perform a thorough analysis of the predicted outcomes. Taken together, misORFPred is a powerful tool for identifying the translatable sORFs in plant pri-miRNAs and can provide highly trusted candidates for subsequent biological experiments.</p>","PeriodicalId":13670,"journal":{"name":"Interdisciplinary Sciences: Computational Life Sciences","volume":" ","pages":"114-133"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell Fate Dynamics Reconstruction Identifies TPT1 and PTPRZ1 Feedback Loops as Master Regulators of Differentiation in Pediatric Glioblastoma-Immune Cell Networks.","authors":"Abicumaran Uthamacumaran","doi":"10.1007/s12539-024-00657-4","DOIUrl":"10.1007/s12539-024-00657-4","url":null,"abstract":"<p><p>Pediatric glioblastoma is a complex dynamical disease that is difficult to treat due to its multiple adaptive behaviors driven largely by phenotypic plasticity. Integrated data science and network theory pipelines offer novel approaches to studying glioblastoma cell fate dynamics, particularly phenotypic transitions over time. Here we used various single-cell trajectory inference algorithms to infer signaling dynamics regulating pediatric glioblastoma-immune cell networks. We identified GATA2, PTPRZ1, TPT1, MTRNR2L1/2, OLIG1/2, SOX11, FXYD6, SEZ6L, PDGFRA, EGFR, S100B, WNT, TNF <math><mi>α</mi></math> , and NF-kB as critical transition genes or signals regulating glioblastoma-immune network dynamics, revealing potential clinically relevant targets. Further, we reconstructed glioblastoma cell fate attractors and found complex bifurcation dynamics within glioblastoma phenotypic transitions, suggesting that a causal pattern may be driving glioblastoma evolution and cell fate decision-making. Together, our findings have implications for developing targeted therapies against glioblastoma, and the continued integration of quantitative approaches and artificial intelligence (AI) to understand pediatric glioblastoma tumor-immune interactions.</p>","PeriodicalId":13670,"journal":{"name":"Interdisciplinary Sciences: Computational Life Sciences","volume":" ","pages":"59-85"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABTrans: A Transformer-based Model for Predicting Interaction between Anti-Aβ Antibodies and Peptides.","authors":"Yuhong Su, Xincheng Zeng, Lingfeng Zhang, Yanlin Bian, Yangjing Wang, Buyong Ma","doi":"10.1007/s12539-024-00664-5","DOIUrl":"10.1007/s12539-024-00664-5","url":null,"abstract":"<p><p>Antibodies against Aβ peptide have been recently approved to treat Alzheimer's disease, underscoring the importance of understanding their interactions for developing more potent treatments. Here we investigated the interaction between anti-Aβ antibodies and various peptides using a deep learning model. Our model, ABTrans, was trained on dodecapeptide sequences from phage display experiments and known anti-Aβ antibody sequences sourced from public sources. It classified the binding ability between anti-Aβ antibodies and dodecapeptides into four levels: not binding, weak binding, medium binding, and strong binding, achieving an accuracy of 0.83. Using ABTrans, we examined the cross-reaction of anti-Aβ antibodies with other human amyloidogenic proteins, revealing that Aducanumab and Donanemab exhibited the least cross-reactivity. Additionally, we systematically screened interactions between eleven selected anti-Aβ antibodies and all human proteins to identify potential off-target candidates.</p>","PeriodicalId":13670,"journal":{"name":"Interdisciplinary Sciences: Computational Life Sciences","volume":" ","pages":"140-152"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cascAGS: Comparative Analysis of SNP Calling Methods for Human Genome Data in the Absence of Gold Standard.","authors":"Qianqian Song, Taobo Hu, Baosheng Liang, Shihai Li, Yang Li, Jinbo Wu, Shu Wang, Xiaohua Zhou","doi":"10.1007/s12539-024-00653-8","DOIUrl":"10.1007/s12539-024-00653-8","url":null,"abstract":"<p><p>The development of third-generation sequencing has accelerated the boom of single nucleotide polymorphism (SNP) calling methods, but evaluating accuracy remains challenging owing to the absence of the SNP gold standard. The definitions for without-gold-standard and performance metrics and their estimation are urgently needed. Additionally, the possible correlations between different SNP loci should also be further explored. To address these challenges, we first introduced the concept of a gold standard and imperfect gold standard under the consistency framework and gave the corresponding definitions of sensitivity and specificity. A latent class model (LCM) was established to estimate the sensitivity and specificity of callers. Furthermore, we incorporated different dependency structures into LCM to investigate their impact on sensitivity and specificity. The performance of LCM was illustrated by comparing the accuracy of BCFtools, DeepVariant, FreeBayes, and GATK on various datasets. Through estimations across multiple datasets, the results indicate that LCM is well-suitable for evaluating callers without the SNP gold standard, and accurate inclusion of the dependency between variations is crucial for better performance ranking. DeepVariant has a higher sum of sensitivity and specificity than other callers, followed by GATK and BCFtools. FreeBayes has low sensitivity but high specificity. Notably, appropriate sequencing coverage is another important factor for precise callers' evaluation. Most importantly, a web interface for assessing and comparing different callers was developed to simplify the evaluation process.</p>","PeriodicalId":13670,"journal":{"name":"Interdisciplinary Sciences: Computational Life Sciences","volume":" ","pages":"1-11"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EfficientNet-resDDSC: A Hybrid Deep Learning Model Integrating Residual Blocks and Dilated Convolutions for Inferring Gene Causality in Single-Cell Data.","authors":"Aimin Li, Mingyue Li, Rong Fei, Saurav Mallik, Bo Hu, Yue Yu","doi":"10.1007/s12539-024-00667-2","DOIUrl":"10.1007/s12539-024-00667-2","url":null,"abstract":"<p><p>Gene Regulatory Networks (GRNs) reveal complex interactions between genes in organisms, crucial for understanding the life system's operation. The rapid development of biotechnology, especially single-cell RNA sequencing (scRNA-seq), has generated a large amount of scRNA-seq data, which can be analyzed to explore the regulatory relationships between genes at the single-cell level. Previous models used to construct GRNs mainly aim at constructing associative relationships between genes, but usually fail to accurately reveal the causality between genes. Therefore, we present a hybrid deep learning model called EfficientNet-resDDSC (the EfficientNet with Residual Blocks and Depthwise Separable Dilated Convolutions) to infer causality between genes. The model inherits the basic structure of EfficientNet-B0 and incorporates residual blocks as well as dilated convolutions. The model's ability to extract low-level features at the primary stage is enhanced by introducing residual blocks. The model combines Depthwise Separable Convolution (DSC) in the inverted linear bottleneck layers with the dilated convolutions to expand the model's receptive fields without increasing the computational effort. This design enables the model to comprehensively reveal potential relationships among different genes in high-dimensional and high-noise single-cell data. In comparison with the five existing deep learning network models, EfficientNet-resDDSC's overall performance is significantly better than others on four datasets. In this study, EfficientNet-resDDSC was further applied to construct GRNs for breast cancer patients, focusing on the related regulatory genes of the key gene BRCA1, which contributes to the advancement of breast cancer research and treatment strategies.</p>","PeriodicalId":13670,"journal":{"name":"Interdisciplinary Sciences: Computational Life Sciences","volume":" ","pages":"166-184"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DeepPD: A Deep Learning Method for Predicting Peptide Detectability Based on Multi-feature Representation and Information Bottleneck.","authors":"Fenglin Li, Yannan Bin, Jianping Zhao, Chunhou Zheng","doi":"10.1007/s12539-024-00665-4","DOIUrl":"10.1007/s12539-024-00665-4","url":null,"abstract":"<p><p>Peptide detectability measures the relationship between the protein composition and abundance in the sample and the peptides identified during the analytical procedure. This relationship has significant implications for the fundamental tasks of proteomics. Existing methods primarily rely on a single type of feature representation, which limits their ability to capture the intricate and diverse characteristics of peptides. In response to this limitation, we introduce DeepPD, an innovative deep learning framework incorporating multi-feature representation and the information bottleneck principle (IBP) to predict peptide detectability. DeepPD extracts semantic information from peptides using evolutionary scale modeling 2 (ESM-2) and integrates sequence and evolutionary information to construct the feature space collaboratively. The IBP effectively guides the feature learning process, minimizing redundancy in the feature space. Experimental results across various datasets demonstrate that DeepPD outperforms state-of-the-art methods. Furthermore, we demonstrate that DeepPD exhibits competitive generalization and transfer learning capabilities across diverse datasets and species. In conclusion, DeepPD emerges as the most effective method for predicting peptide detectability, showcasing its potential applicability to other protein sequence prediction tasks.</p>","PeriodicalId":13670,"journal":{"name":"Interdisciplinary Sciences: Computational Life Sciences","volume":" ","pages":"200-214"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI Prediction of Structural Stability of Nanoproteins Based on Structures and Residue Properties by Mean Pooled Dual Graph Convolutional Network.","authors":"Daixi Li, Yuqi Zhu, Wujie Zhang, Jing Liu, Xiaochen Yang, Zhihong Liu, Dongqing Wei","doi":"10.1007/s12539-024-00662-7","DOIUrl":"10.1007/s12539-024-00662-7","url":null,"abstract":"<p><p>The structural stability of proteins is an important topic in various fields such as biotechnology, pharmaceuticals, and enzymology. Specifically, understanding the structural stability of protein is crucial for protein design. Artificial design, while pursuing high thermodynamic stability and rigidity of proteins, inevitably sacrifices biological functions closely related to protein flexibility. The thermodynamic stability of proteins is not always optimal when they are highest to perfectly perform their biological functions. Extensive theoretical and experimental screening is often required to obtain stable protein structures. Thus, it becomes critically important to develop a stability prediction model based on the balance between protein stability and bioactivity. To design protein drugs with better functionality in a broader structural space, a novel protein structural stability predictor called PSSP has been developed in this study. PSSP is a mean pooled dual graph convolutional network (GCN) model based on sequence characteristics and secondary structure, distance matrix, graph, and residue properties of a nanoprotein to provide rapid prediction and judgment. This model exhibits excellent robustness in predicting the structural stability of nanoproteins. Comparing with previous artificial intelligence algorithms, the results indicate this model can provide a rapid and accurate assessment of the structural stability of artificially designed proteins, which shows the great promises for promoting the robust development of protein design.</p>","PeriodicalId":13670,"journal":{"name":"Interdisciplinary Sciences: Computational Life Sciences","volume":" ","pages":"101-113"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}