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Protein is one of the most significant components of all living creatures. All significant and essential biological structures and functions relies on proteins and their respective biological functions. However, proteins cannot perform their unique biological significance independently. They have to interact with each other to realize the complicated biological processes in all living creatures including human beings. In other words, proteins depend on interactions (protein-protein interactions) to realize their significant effects. Thus, the significance comparison and quantitative contribution of candidate PPI features must be determined urgently. According to previous studies, 258 physical and chemical characteristics of proteins have been reported and confirmed to definitively affect the interaction efficiency of the related proteins. Among such features, essential physiochemical features of proteins like stoichiometric balance, protein abundance, molecular weight and charge distribution have been validated to be quite significant and irreplaceable for protein-protein interactions (PPIs). Therefore, in this study, we, on one hand, presented a novel computational framework to identify the key factors affecting PPIs with Boruta feature selection (BFS), Monte Carlo feature selection (MCFS), incremental feature selection (IFS), and on the other hand, built a quantitative decision-rule system to evaluate the potential PPIs under real conditions with random forest (RF) and RIPPER algorithms, thereby supplying several new insights into the detailed biological mechanisms of complicated PPIs. The main datasets and codes can be downloaded at https://github.com/xypan1232/Mass-PPI.

DNA methylation is an essential epigenetic modification for multiple biological processes. DNA methylation in mammals acts as an epigenetic mark of transcriptional repression. Aberrant levels of DNA methylation can be observed in various types of tumor cells. Thus, DNA methylation has attracted considerable attention among researchers to provide new and feasible tumor therapies. Conventional studies considered single-gene methylation or specific loci as biomarkers for tumorigenesis. However, genome-scale methylated modification has not been completely investigated. Thus, we proposed and compared two novel computational approaches based on multiple machine learning algorithms for the qualitative and quantitative analyses of methylation-associated genes and their dys-methylated patterns. This study contributes to the identification of novel effective genes and the establishment of optimal quantitative rules for aberrant methylation distinguishing tumor cells with different origin tissues.

Single-cell sequencing technologies have emerged to address new and longstanding biological and biomedical questions. Previous studies focused on the analysis of bulk tissue samples composed of millions of cells. However, the genomes within the cells of an individual multicellular organism are not always the same. In this study, we aimed to identify the crucial and characteristically expressed genes that may play functional roles in tissue development and organogenesis, by analyzing a single-cell transcriptomic atlas of mice. We identified the most relevant gene features and decision rules classifying 18 cell categories, providing a list of genes that may perform important functions in the process of tissue development because of their tissue-specific expression patterns. These genes may serve as biomarkers to identify the origin of unknown cell subgroups so as to recognize specific cell stages/states during the dynamic process, and also be applied as potential therapy targets for developmental disorders.

Copy number variation (CNV) is a common structural variation pattern of DNA, and it features a higher mutation rate than single-nucleotide polymorphisms (SNPs) and affects a larger fragment of genomes. CNV is related with the genesis of complex diseases and can thus be used as a strategy to identify novel cancer-predisposing markers or mechanisms. In particular, the frequent deletions of mono-ADP-ribosylhydrolase 2 (MACROD2) locus in human colorectal cancer (CRC) alters DNA repair and the sensitivity to DNA damage and results in chromosomal instability. The relationship between CNV and cancer has not been explained. In this study, on the basis of the genome variation profiling by the SNP array from 651 CRC primary tumors, we computationally analyzed the CNV data to select crucial SNP sites with the most relevance to three different states of MACROD2 (heterozygous deletion, homozygous deletion, and normal state), suggesting that these CNVs may play functional roles in CRC tumorigenesis. Our study can shed new insights into the genesis of cancer based on CNV, providing reference for clinical diagnosis, and treatment prognosis of CRC.

Isocitrate dehydrogenase (IDH) is an oncogene, and the expression of a mutated IDH promotes cell proliferation and inhibits cell differentiation. IDH exists in three different isoforms, whose mutation can cause many solid tumors, especially gliomas in adults. No effective method for classifying gliomas on genetic signatures is currently available. DNA methylation may be applied to distinguish cancer cells from normal tissues. In this study, we focused on three subtypes of IDH-mutation gliomas by examining methylation data. Several advanced computational methods were used, such as Monte Carlo feature selection (MCFS), incremental feature selection (IFS), support machine vector (SVM), etc. The MCFS method was adopted to analyze methylation features, resulting in a feature list. Then, the IFS method incorporating SVM was applied to the list to extract important methylation features and construct an optimal SVM classifier. As a result, several methylation features (sites) were found to relate to glioma subclasses, which are annotated onto multiple genes, such as FLJ37543, LCE3D, FAM89A, ADCY5, ESR1, C2orf67, REST, EPHA7, etc. These genes are enriched in biological functions, including cellular developmental process, neuron differentiation, cellular component morphogenesis, and G-protein-coupled receptor signaling pathway. Our results, which are supported by literature reports and independent dataset validation, showed that our identified genes and functions contributed to the detailed glioma subtypes. This study provided a basic research on IDH-mutation gliomas.

Liquid biopsy (i.e., fluid biopsy) involves a series of clinical examination approaches. Monitoring of cancer immunological status by the “immunosignature” of patients presents a novel method for tumor-associated liquid biopsy. The major work content and the core technological difficulties for the monitoring of cancer immunosignature are the recognition of cancer-related immune-activating antigens by high-throughput screening approaches. Currently, one key task of immunosignature-based liquid biopsy is the qualitative and quantitative identification of typical tumor-specific antigens. In this study, we reused two sets of peptide microarray data that detected the expression level of potential antigenic peptides derived from tumor tissues to avoid the detection differences induced by chip platforms. Several machine learning algorithms were applied on these two sets. First, the Monte Carlo Feature Selection (MCFS) method was used to analyze features in two sets. A feature list was obtained according to the MCFS results on each set. Second, incremental feature selection method incorporating one classification algorithm (support vector machine or random forest) followed to extract optimal features and construct optimal classifiers. On the other hand, the repeated incremental pruning to produce error reduction, a rule learning algorithm, was applied on key features yielded by the MCFS method to extract quantitative rules for accurate cancer immune monitoring and pathologic diagnosis. Finally, obtained key features and quantitative rules were extensively analyzed.