Lei Zheng

Bio: Lei Zheng is an academic researcher from Inner Mongolia University. The author has contributed to research in topics: Feature selection & Computational biology. The author has an hindex of 6, co-authored 14 publications receiving 123 citations.

RAACBook: a web server of reduced amino acid alphabet for sequence-dependent inference by using Chou's five-step rule.

Abstract: By reducing amino acid alphabet, the protein complexity can be significantly simplified, which could improve computational efficiency, decrease information redundancy and reduce chance of overfitting. Although some reduced alphabets have been proposed, different classification rules could produce distinctive results for protein sequence analysis. Thus, it is urgent to construct a systematical frame for reduced alphabets. In this work, we constructed a comprehensive web server called RAACBook for protein sequence analysis and machine learning application by integrating reduction alphabets. The web server contains three parts: (i) 74 types of reduced amino acid alphabet were manually extracted to generate 673 reduced amino acid clusters (RAACs) for dealing with unique protein problems. It is easy for users to select desired RAACs from a multilayer browser tool. (ii) An online tool was developed to analyze primary sequence of protein. The tool could produce K-tuple reduced amino acid composition by defining three correlation parameters (K-tuple, g-gap, λ-correlation). The results are visualized as sequence alignment, mergence of RAA composition, feature distribution and logo of reduced sequence. (iii) The machine learning server is provided to train the model of protein classification based on K-tuple RAAC. The optimal model could be selected according to the evaluation indexes (ROC, AUC, MCC, etc.). In conclusion, RAACBook presents a powerful and user-friendly service in protein sequence analysis and computational proteomics. RAACBook can be freely available at http://bioinfor.imu.edu.cn/raacbook. Database URL: http://bioinfor.imu.edu.cn/raacbook.

RaacLogo: a new sequence logo generator by using reduced amino acid clusters.

Abstract: Sequence logos give a fast and concise display in visualizing consensus sequence. Protein exhibits greater complexity and diversity than DNA, which usually affects the graphical representation of the logo. Reduced amino acids perform powerful ability for simplifying complexity of sequence alignment, which motivated us to establish RaacLogo. As a new sequence logo generator by using reduced amino acid alphabets, RaacLogo can easily generate many different simplified logos tailored to users by selecting various reduced amino acid alphabets that consisted of more than 40 clustering algorithms. This current web server provides 74 types of reduced amino acid alphabet, which were manually extracted to generate 673 reduced amino acid clusters (RAACs) for dealing with protein alignment. A two-dimensional selector was proposed for easily selecting desired RAACs with underlying biology knowledge. It is anticipated that the RaacLogo web server will play more high-potential roles for protein sequence alignment, topological estimation and protein design experiments. RaacLogo is freely available at http://bioinfor.imu.edu.cn/raaclogo.

EmExplorer: a database for exploring time activation of gene expression in mammalian embryos.

Abstract: Understanding early development offers a striking opportunity to investigate genetic disease, stem cell and assisted reproductive technology. Recent advances in high-throughput sequencing technology have led to the rising influx of omics data, which have rapidly boosted our understanding of mammalian developmental mechanisms. Here, we review the database EmExplorer (a database for exploring time activation of gene expression in mammalian embryos), which systematically organizes the genes from development-related pathways, and which we have already established and continue to update it. The current version of EmExplorer incorporates over 26 000 genes obtained from 306 functional pathways in five species. The function annotations of development-related genes were also integrated into EmExplorer. To facilitate data extraction, the database also contains the following information. (i) The dynamic expression values for each development stage are matched to the corresponding genes. (ii) A two-layer search tool which supports multi-option searching, such as by official symbol, pathway name and function annotation. The returned entries can directly link to the analysis results for the corresponding gene or pathway in the analysis module. (iii) The analysis module provides different gene comparisons at the multi-species level and functional pathway level, which shows the species specificity and stage specificity at the gene or pathway level. (iv) The analysis based on the hypergeometric distribution test reveals the enrichment of gene functions at a particular stage of one organism's pathway. (v) The browser is designed for users with ambiguous searching goals and greatly helps new users to get a general idea of the contents of the database. (vi) The experimentally validated pathways are manually curated and shown on the home page. EmExplorer will be helpful for elucidating early developmental mechanisms and exploring time activation genes. EmExplorer is freely available at http://bioinfor.imu.edu.cn/emexplorer .

Machine Learning of Single-Cell Transcriptome Highly Identifies mRNA Signature by Comparing F-Score Selection with DGE Analysis

Abstract: Human preimplantation development is a complex process involving dramatic changes in transcriptional architecture. For a better understanding of their time-spatial development, it is indispensable to identify key genes. Although the single-cell RNA sequencing (RNA-seq) techniques could provide detailed clustering signatures, the identification of decisive factors remains difficult. Additionally, it requires high experimental cost and a long experimental period. Thus, it is highly desired to develop computational methods for identifying effective genes of development signature. In this study, we first developed a predictor called EmPredictor to identify developmental stages of human preimplantation embryogenesis. First, we compared the F-score of feature selection algorithms with differential gene expression (DGE) analysis to find specific signatures of the development stage. In addition, by training the support vector machine (SVM), four types of signature subsets were comprehensively discussed. The prediction results showed that a feature subset with 1,881 genes from the F-score algorithm obtained the best predictive performance, which achieved the highest accuracy of 93.3% on the cross-validation set. Further function enrichment demonstrated that the gene set selected by the feature selection method was involved in more development-related pathways and cell fate determination biomarkers. This indicates that the F-score algorithm should be preferentially proposed for detecting key genes of multi-period data in mammalian early development.

A Comparative Analysis of Single-Cell Transcriptome Identifies Reprogramming Driver Factors for Efficiency Improvement

Abstract: Terminally differentiated somatic cells can be reprogrammed into a totipotent state through somatic cell nuclear transfer (SCNT). The incomplete reprogramming is the major reason for developmental arrest of SCNT embryos at early stages. In our studies, we found that pathways for autophagy, endocytosis, and apoptosis were incompletely activated in nuclear transfer (NT) 2-cell arrest embryos, whereas extensively inhibited pathways for stem cell pluripotency maintenance, DNA repair, cell cycle, and autophagy may result in NT 4-cell embryos arrest. As for NT normal embryos, a significant shift in expression of developmental transcription factors (TFs) Id1, Pou6f1, Cited1, and Zscan4c was observed. Compared with pluripotent gene Ascl2 being activated only in NT 2-cell, Nanog, Dppa2, and Sall4 had major expression waves in normal development of both NT 2-cell and 4-cell embryos. Additionally, Kdm4b/4d and Kdm5b had been confirmed as key markers in NT 2-cell and 4-cell embryos, respectively. Histone acetylases Kat8, Elp6, and Eid1 were co-activated in NT 2-cell and 4-cell embryos to facilitate normal development. Gadd45a as a key driver functions with Tet1 and Tet2 to improve the efficiency of NT reprogramming. Taken together, our findings provided an important theoretical basis for elucidating the potential molecular mechanisms and identified reprogramming driver factor to improve the efficiency of SCNT reprogramming.

Predicting Thermophilic Proteins by Machine Learning

Abstract: Thermophilic proteins can maintain good activity under high temperature, therefore, it is important to study thermophilic proteins for the thermal stability of proteins. In order to solve the problem of low precision and low efficiency in predicting thermophilic proteins, a prediction method based on feature fusion and machine learning was proposed in this paper. For the selected thermophilic data sets, firstly, the thermophilic protein sequence was characterized based on feature fusion by the combination of g-gap dipeptide, entropy density and autocorrelation coefficient. Then, Kernel Principal Component Analysis (KPCA) was used to reduce the dimension of the expressed protein sequence features in order to reduce the training time and improve efficiency. Finally, the classification model was designed by using the classification algorithm. A variety of classification algorithms was used to train and test on the selected thermophilic dataset. By comparison, the accuracy of the Support Vector Machine (SVM) under the jackknife method was over 92%. The combination of other evaluation indicators also proved that the SVM performance was the best. Because of choosing an effectively feature representation method and a robust classifier, the proposed method is suitable for predicting thermophilic proteins and is superior to most reported methods.

Immune cell infiltration-based signature for prognosis and immunogenomic analysis in breast cancer

Abstract: Breast cancer is one of the most human malignant diseases and the leading cause of cancer-related death in the world. However, the prognostic and therapeutic benefits of breast cancer patients cannot be predicted accurately by the current stratifying system. In this study, an immune-related prognostic score was established in 22 breast cancer cohorts with a total of 6415 samples. An extensive immunogenomic analysis was conducted to explore the relationships between immune score, prognostic significance, infiltrating immune cells, cancer genotypes and potential immune escape mechanisms. Our analysis revealed that this immune score was a promising biomarker for estimating overall survival in breast cancer. This immune score was associated with important immunophenotypic factors, such as immune escape and mutation load. Further analysis revealed that patients with high immune scores exhibited therapeutic benefits from chemotherapy and immunotherapy. Based on these results, we can conclude that this immune score may be a useful tool for overall survival prediction and treatment guidance for patients with breast cancer.

Computational identification of N6-methyladenosine sites in multiple tissues of mammals.

Abstract: N6-methyladenosine (m6A) is the methylation of the adenosine at the nitrogen-6 position, which is the most abundant RNA methylation modification and involves a series of important biological processes. Accurate identification of m6A sites in genome-wide is invaluable for better understanding their biological functions. In this work, an ensemble predictor named iRNA-m6A was established to identify m6A sites in multiple tissues of human, mouse and rat based on the data from high-throughput sequencing techniques. In the proposed predictor, RNA sequences were encoded by physical-chemical property matrix, mono-nucleotide binary encoding and nucleotide chemical property. Subsequently, these features were optimized by using minimum Redundancy Maximum Relevance (mRMR) feature selection method. Based on the optimal feature subset, the best m6A classification models were trained by Support Vector Machine (SVM) with 5-fold cross-validation test. Prediction results on independent dataset showed that our proposed method could produce the excellent generalization ability. We also established a user-friendly webserver called iRNA-m6A which can be freely accessible at http://lin-group.cn/server/iRNA-m6A. This tool will provide more convenience to users for studying m6A modification in different tissues.

iDNA6mA-Rice: A Computational Tool for Detecting N6-Methyladenine Sites in Rice.

Abstract: DNA N6-methyladenine (6mA) is a dominant DNA modification form and involved in many biological functions. The accurate genome-wide identification of 6mA sites may increase understanding of its biological functions. Experimental methods for 6mA detection in eukaryotes genome are laborious and expensive. Therefore, it is necessary to develop computational methods to identify 6mA sites on a genomic scale, especially for plant genomes. Based on this consideration, the study aims to develop a machine learning-based method of predicting 6mA sites in the rice genome. We initially used mono-nucleotide binary encoding to formulate positive and negative samples. Subsequently, the machine learning algorithm named Random Forest was utilized to perform the classification for identifying 6mA sites. Our proposed method could produce an area under the receiver operating characteristic curve of 0.964 with an overall accuracy of 0.917, as indicated by the fivefold cross-validation test. Furthermore, an independent dataset was established to assess the generalization ability of our method. Finally, an area under the receiver operating characteristic curve of 0.981 was obtained, suggesting that the proposed method had good performance of predicting 6mA sites in the rice genome. For the convenience of retrieving 6mA sites, on the basis of the computational method, we built a freely accessible web server named iDNA6mA-Rice at http://lin-group.cn/server/iDNA6mA-Rice.

RAACBook: a web server of reduced amino acid alphabet for sequence-dependent inference by using Chou's five-step rule.

Abstract: By reducing amino acid alphabet, the protein complexity can be significantly simplified, which could improve computational efficiency, decrease information redundancy and reduce chance of overfitting. Although some reduced alphabets have been proposed, different classification rules could produce distinctive results for protein sequence analysis. Thus, it is urgent to construct a systematical frame for reduced alphabets. In this work, we constructed a comprehensive web server called RAACBook for protein sequence analysis and machine learning application by integrating reduction alphabets. The web server contains three parts: (i) 74 types of reduced amino acid alphabet were manually extracted to generate 673 reduced amino acid clusters (RAACs) for dealing with unique protein problems. It is easy for users to select desired RAACs from a multilayer browser tool. (ii) An online tool was developed to analyze primary sequence of protein. The tool could produce K-tuple reduced amino acid composition by defining three correlation parameters (K-tuple, g-gap, λ-correlation). The results are visualized as sequence alignment, mergence of RAA composition, feature distribution and logo of reduced sequence. (iii) The machine learning server is provided to train the model of protein classification based on K-tuple RAAC. The optimal model could be selected according to the evaluation indexes (ROC, AUC, MCC, etc.). In conclusion, RAACBook presents a powerful and user-friendly service in protein sequence analysis and computational proteomics. RAACBook can be freely available at http://bioinfor.imu.edu.cn/raacbook. Database URL: http://bioinfor.imu.edu.cn/raacbook.