Journal of Bioinformatics and Computational Biology最新文献

{"title":"Transforming OMIC features for classification using siamese convolutional networks.","authors":"Qian Wang,&nbsp;Meiyu Duan,&nbsp;Yusi Fan,&nbsp;Shuai Liu,&nbsp;Yanjiao Ren,&nbsp;Lan Huang,&nbsp;Fengfeng Zhou","doi":"10.1142/S0219720022500135","DOIUrl":"https://doi.org/10.1142/S0219720022500135","url":null,"abstract":"<p><p>Modern biotechnologies have generated huge amount of OMIC data, among which transcriptomes and methylomes are two major OMIC types. Transcriptomes measure the expression levels of all the transcripts while methylomes depict the cytosine methylation levels across a genome. Both OMIC data types could be generated by array or sequencing. And some studies deliver many more features (the number of features is denoted as [Formula: see text]) for a sample than the number [Formula: see text] of samples in a cohort, which induce the \"large [Formula: see text] small [Formula: see text]\" paradigm. This study focused on the classification problem about OMIC with \"large [Formula: see text] small [Formula: see text]\" paradigm. A Siamese convolutional network was utilized to transform the OMIC features into a new space with minimized intra-class distances and maximized inter-class distances between the samples. The proposed feature engineering algorithm SiaCo was comprehensively evaluated using both transcriptome and methylome datasets. The experimental data showed that SiaCo generated SiaCo features with improved classification accuracies for binary classification problems, and achieved improvements on the independent test dataset. The individual SiaCo features did not show better inter-class discrimination powers than the original OMIC features. This may be due to that the Siamese convolutional network optimized the collective performances of the SiaCo features, instead of the individual feature's discrimination power. The inherent transformation nature of the Siamese twin network also makes the SiaCo features lack of interpretability. The source code of SiaCo is freely available at http://www.healthinformaticslab.org/supp/resources.php.</p>","PeriodicalId":48910,"journal":{"name":"Journal of Bioinformatics and Computational Biology","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40608394","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":"Prediction model for synergistic anti-tumor multi-compound combinations from traditional Chinese medicine based on extreme gradient boosting, targets and gene expression data.","authors":"Mengqiu Sun,&nbsp;Shengnan She,&nbsp;Hengwei Chen,&nbsp;Jiaxi Cheng,&nbsp;Wei Ji,&nbsp;Dan Wang,&nbsp;Chunlai Feng","doi":"10.1142/S0219720022500160","DOIUrl":"https://doi.org/10.1142/S0219720022500160","url":null,"abstract":"<p><p>Traditional Chinese medicine (TCM) is characterized by synergistic therapeutic effect involving multiple compounds and targets, which provide potential new therapy for the treatment of complex cancer conditions. However, the main contributors and the underlying mechanisms of synergistic TCM cancer therapies remain largely undetermined. Machine learning now provides a new approach to determine synergistic compound combinations from complex components of TCM. In this study, a prediction model based on extreme gradient boosting (XGBoost) algorithm was constructed by integrating gene expression data of different cancer cell lines, targets information of natural compounds and drug response data. Radix Paeoniae Rubra (RPR) was selected as a model herbal sample to evaluate the reliability of the constructed model. The optimal XGBoost prediction model achieved a good performance with Mean Square Error (MSE) of 0.66, Mean Absolute Error (MAE) of 0.61, and the Root Mean Squared Error (RMSE) of 0.81 on test dataset. The superior synergistic anti-tumor combinations of D15 (Paeonol[Formula: see text][Formula: see text][Formula: see text]Ethyl gallate) and D13 (Paeoniflorin[Formula: see text][Formula: see text][Formula: see text]Paeonol) were successfully predicted from RPR and experimentally validated on MCF-7 cells. Moreover, the combination of D13 could work as a main contributor to a synergistic anti-proliferative activity in the compatibility of RPR and Cortex Moutan (CM). Our XGBoost model could be a reliable tool for the efficient prediction of synergistic anti-tumor multi-compound combinations from TCM.</p>","PeriodicalId":48910,"journal":{"name":"Journal of Bioinformatics and Computational Biology","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40624490","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":"Automated analysis of karyotype images.","authors":"Ensieh Khazaei,&nbsp;Ala Emrany,&nbsp;Mostafa Tavassolipour,&nbsp;Foroozandeh Mahjoubi,&nbsp;Ahmad Ebrahimi,&nbsp;Seyed Abolfazl Motahari","doi":"10.1142/S0219720022500111","DOIUrl":"https://doi.org/10.1142/S0219720022500111","url":null,"abstract":"<p><p>Karyotype is a genetic test that is used for detection of chromosomal defects. In a karyotype test, an image is captured from chromosomes during the cell division. The captured images are then analyzed by cytogeneticists in order to detect possible chromosomal defects. In this paper, we have proposed an automated pipeline for analysis of karyotype images. There are three main steps for karyotype image analysis: image enhancement, image segmentation and chromosome classification. In this paper, we have proposed a novel chromosome segmentation algorithm to decompose overlapped chromosomes. We have also proposed a CNN-based classifier which outperforms all the existing classifiers. Our classifier is trained by a dataset of about 1,62,000 human chromosome images. We also introduced a novel post-processing algorithm which improves the classification results. The success rate of our segmentation algorithm is 95%. In addition, our experimental results show that the accuracy of our classifier for human chromosomes is 92.63% and our novel post-processing algorithm increases the classification results to 94%.</p>","PeriodicalId":48910,"journal":{"name":"Journal of Bioinformatics and Computational Biology","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40494201","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":"Prediction of nucleosome dynamic interval based on long-short-term memory network (LSTM)","authors":"Jianli Liu, D. Zhou, Wen Jin","doi":"10.1142/S0219720022500093","DOIUrl":"https://doi.org/10.1142/S0219720022500093","url":null,"abstract":"Nucleosome localization is a dynamic process and consists of nucleosome dynamic intervals (NDIs). We preprocessed nucleosome sequence data as time series data (TSD) and developed a long short-term memory network (LSTM) model for training time series data (TSD; LSTM-TSD model) using iterative training and feature learning that predicts NDIs with high accuracy. Sn, Sp, Acc, and MCC of the obtained LSTM model is 91.88%, 92.72%, 92.30%, and 84.61%, respectively. LSTM model could precisely predict the NDIs of yeast 16 chromosome. The NDIs contain 90.29% of nucleosome core DNA and 91.20% of nucleosome central sites, indicating that NDIs have high confidence. We found that the binding sites of transcriptional proteins and other proteins are outside NDIs, not in NDIs. These results are important for analysis of nucleosome localization and gene transcriptional regulation.","PeriodicalId":48910,"journal":{"name":"Journal of Bioinformatics and Computational Biology","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48943898","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":"Denoising of scanning electron microscope images for biological ultrastructure enhancement","authors":"Sheng Chang, Lijun Shen, Linlin Li, Xi Chen, Hua Han","doi":"10.1142/S021972002250007X","DOIUrl":"https://doi.org/10.1142/S021972002250007X","url":null,"abstract":"Scanning electron microscopy (SEM) is of great significance for analyzing the ultrastructure. However, due to the requirements of data throughput and electron dose of biological samples in the imaging process, the SEM image of biological samples is often occupied by noise which severely affects the observation of ultrastructure. Therefore, it is necessary to analyze and establish a noise model of SEM and propose an effective denoising algorithm that can preserve the ultrastructure. We first investigated the noise source of SEM images and introduced a signal-related SEM noise model. Then, we validated the effectiveness of the noise model through experiments, which are designed with standard samples to reflect the relation between real signal intensity and noise. Based on the SEM noise model and traditional variance stabilization denoising strategy, we proposed a novel, two-stage denoising method. In the first stage variance stabilization, our VS-Net realizes the separation of signal-dependent noise and signal in the SEM image. In the second stage denoising, our D-Net employs the structure of U-Net and combines the attention mechanism to achieve efficient noise removal. Compared with other existing denoising methods for SEM images, our proposed method is more competitive in objective evaluation and visual effects. Source code is available on GitHub (https://github.com/VictorCSheng/VSID-Net).","PeriodicalId":48910,"journal":{"name":"Journal of Bioinformatics and Computational Biology","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46938369","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":"Quantitative structure-activity relationship modeling reveals the minimal sequence requirement and amino acid preference of sirtuin-1's deacetylation substrates in diabetes mellitus","authors":"X. Shao, W. Kong, Y. Li, S. Zhang","doi":"10.1142/S0219720022500081","DOIUrl":"https://doi.org/10.1142/S0219720022500081","url":null,"abstract":"Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD[Formula: see text]-dependent deacetylase involved in multiple glucose metabolism pathways and plays an important role in the pathogenesis of diabetes mellitus (DM). The enzyme specifically recognizes its deacetylation substrates' peptide segments containing a central acetyl-lysine residue as well as a number of amino acids flanking the central residue. In this study, we attempted to ascertain the minimal sequence requirement (MSR) around the central acetyl-lysine residue of SIRT1 substrate-recognition sites as well as the amino acid preference (AAP) at different residues of the MSR window through quantitative structure-activity relationship (QSAR) strategy, which would benefit our understanding of SIRT1 substrate specificity at the molecular level and is also helpful to rationally design substrate-mimicking peptidic agents against DM by competitively targeting SIRT1 active site. In this procedure, a large-scale dataset containing 6801 13-mer acetyl-lysine peptides (and their SIRT1-catalyized deacetylation activities) were compiled to train 10 QSAR regression models developed by systematic combination of machine learning methods (PLS and SVM) and five amino acids descriptors (DPPS, T-scale, MolSurf, [Formula: see text]-score, and FASGAI). The two best QSAR models (PLS+FASGAI and SVM+DPPS) were then employed to statistically examine the contribution of residue positions to the deacetylation activity of acetyl-lysine peptide substrates, revealing that the MSR can be represented by 5-mer acetyl-lysine peptides that meet a consensus motif X[Formula: see text]X[Formula: see text]X[Formula: see text](AcK)0X[Formula: see text]. Structural analysis found that the X[Formula: see text] and (AcK)0 residues are tightly packed against the enzyme active site and confer both stability and specificity for the enzyme-substrate complex, whereas the X[Formula: see text], X[Formula: see text] and X[Formula: see text] residues are partially exposed to solvent but can also effectively stabilize the complex system. Subsequently, a systematic deacetylation activity change profile (SDACP) was created based on QSAR modeling, from which the AAP for each residue position of MSR was depicted. With the profile, we were able to rationally design an SDACP combinatorial library with promising deacetylation activity, from which nine MSR acetyl-lysine peptides as well as two known SIRT1 acetyl-lysine peptide substrates were tested by using SIRT1 deacetylation assay. It is revealed that the designed peptides exhibit a comparable or even higher activity than the controls, although the former is considerably shorter than the latter.","PeriodicalId":48910,"journal":{"name":"Journal of Bioinformatics and Computational Biology","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45781245","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":"DeepBtoD: Improved RNA-binding proteins prediction via integrated deep learning","authors":"Xiuquan Du, Xiu-juan Zhao, Yanping Zhang","doi":"10.1142/S0219720022500068","DOIUrl":"https://doi.org/10.1142/S0219720022500068","url":null,"abstract":"RNA-binding proteins (RBPs) have crucial roles in various cellular processes such as alternative splicing and gene regulation. Therefore, the analysis and identification of RBPs is an essential issue. However, although many computational methods have been developed for predicting RBPs, a few studies simultaneously consider local and global information from the perspective of the RNA sequence. Facing this challenge, we present a novel method called DeepBtoD, which predicts RBPs directly from RNA sequences. First, a [Formula: see text]-BtoD encoding is designed, which takes into account the composition of [Formula: see text]-nucleotides and their relative positions and forms a local module. Second, we designed a multi-scale convolutional module embedded with a self-attentive mechanism, the ms-focusCNN, which is used to further learn more effective, diverse, and discriminative high-level features. Finally, global information is considered to supplement local modules with ensemble learning to predict whether the target RNA binds to RBPs. Our preliminary 24 independent test datasets show that our proposed method can classify RBPs with the area under the curve of 0.933. Remarkably, DeepBtoD shows competitive results across seven state-of-the-art methods, suggesting that RBPs can be highly recognized by integrating local [Formula: see text]-BtoD and global information only from RNA sequences. Hence, our integrative method may be useful to improve the power of RBPs prediction, which might be particularly useful for modeling protein-nucleic acid interactions in systems biology studies. Our DeepBtoD server can be accessed at http://175.27.228.227/DeepBtoD/.","PeriodicalId":48910,"journal":{"name":"Journal of Bioinformatics and Computational Biology","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42540334","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":"RPfam: A refiner towards curated-like multiple sequence alignments of the Pfam protein families","authors":"Qingting Wei, Hong Zou, Cuncong Zhong, Jianfeng Xu","doi":"10.1142/S0219720022400029","DOIUrl":"https://doi.org/10.1142/S0219720022400029","url":null,"abstract":"High-quality multiple sequence alignments can provide insights into the architecture and function of protein families. The existing MSA tools often generate results inconsistent with biological distribution of conserved regions because of positioning amino acid residues and gaps only by symbols. We propose RPfam, a refiner towards curated-like MSAs for modeling the protein families in the Pfam database. RPfam refines the automatic alignments via scoring alignments based on the PFASUM matrix, restricting realignments within badly aligned blocks, optimizing the block scores by dynamic programming, and running refinements iteratively using the Simulated Annealing algorithm. Experiments show RPfam effectively refined the alignments produced by the MSA tools ClustalO and Muscle with reference to the curated seed alignments of the Pfam protein families. Especially RPfam improved the quality of the ClustalO alignments by 4.4% and the Muscle alignments by 2.8% on the gp32 DNA binding protein-like family. Supplementary Table is available at http://www.worldscinet.com/jbcb/.","PeriodicalId":48910,"journal":{"name":"Journal of Bioinformatics and Computational Biology","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48191874","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":"Analysis to determine the effect of mutations on binding to small chemical molecules","authors":"T. Koshlan, K. Kulikov","doi":"10.1142/S0219720022400030","DOIUrl":"https://doi.org/10.1142/S0219720022400030","url":null,"abstract":"In this paper, the authors present and describe, in detail, an original software-implemented numerical methodology used to determine the effect of mutations on binding to small chemical molecules, on the example of gefitinib, AMPPNP, CO-1686, ASP8273, erlotinib binding with EGFR protein, and imatinib binding with PPARgamma. Furthermore, the developed numerical approach makes it possible to determine the stability of a molecular complex, which consists of a protein and a small chemical molecule. The description of the software package that implements the presented algorithm is given in the website: https://binomlabs.com/.","PeriodicalId":48910,"journal":{"name":"Journal of Bioinformatics and Computational Biology","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47358607","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":"Clinical drug response prediction from preclinical cancer cell lines by logistic matrix factorization approach.","authors":"Akram Emdadi,&nbsp;Changiz Eslahchi","doi":"10.1142/S0219720021500359","DOIUrl":"https://doi.org/10.1142/S0219720021500359","url":null,"abstract":"<p><p>Predicting tumor drug response using cancer cell line drug response values for a large number of anti-cancer drugs is a significant challenge in personalized medicine. Predicting patient response to drugs from data obtained from preclinical models is made easier by the availability of different knowledge on cell lines and drugs. This paper proposes the TCLMF method, a predictive model for predicting drug response in tumor samples that was trained on preclinical samples and is based on the logistic matrix factorization approach. The TCLMF model is designed based on gene expression profiles, tissue type information, the chemical structure of drugs and drug sensitivity (<i>IC</i> 50) data from cancer cell lines. We use preclinical data from the Genomics of Drug Sensitivity in Cancer dataset (GDSC) to train the proposed drug response model, which we then use to predict drug sensitivity of samples from the Cancer Genome Atlas (TCGA) dataset. The TCLMF approach focuses on identifying successful features of cell lines and drugs in order to calculate the probability of the tumor samples being sensitive to drugs. The closest cell line neighbours for each tumor sample are calculated using a description of similarity between tumor samples and cell lines in this study. The drug response for a new tumor is then calculated by averaging the low-rank features obtained from its neighboring cell lines. We compare the results of the TCLMF model with the results of the previously proposed methods using two databases and two approaches to test the model's performance. In the first approach, 12 drugs with enough known clinical drug response, considered in previous methods, are studied. For 7 drugs out of 12, the TCLMF can significantly distinguish between patients that are resistance to these drugs and the patients that are sensitive to them. These approaches are converted to classification models using a threshold in the second approach, and the results are compared. The results demonstrate that the TCLMF method provides accurate predictions across the results of the other algorithms. Finally, we accurately classify tumor tissue type using the latent vectors obtained from TCLMF's logistic matrix factorization process. These findings demonstrate that the TCLMF approach produces effective latent vectors for tumor samples. The source code of the TCLMF method is available in https://github.com/emdadi/TCLMF.</p>","PeriodicalId":48910,"journal":{"name":"Journal of Bioinformatics and Computational Biology","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39614910","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}