Abstract With advances in sequencing and instrument technology, bioinformatics analysis is being applied to batches of massive cells at single-cell resolution. High-throughput single-cell sequencing can be utilized for multi-omics characterization of tumor cells, stromal cells or infiltrated immune cells to evaluate tumor progression, responses to environmental perturbations, heterogeneous composition of the tumor microenvironment, and complex intercellular interactions between these factors. Particularly, single-cell sequencing of T cell receptors, alone or in combination with single-cell RNA sequencing, is useful in the fields of tumor immunology and immunotherapy. Clinical insights obtained from single-cell analysis are critically important for exploring the biomarkers of disease progression or antitumor treatment, as well as for guiding precise clinical decision-making for patients with malignant tumors. In this review, we summarize the clinical applications of single-cell sequencing in the fields of tumor cell evolution, tumor immunology, and tumor immunotherapy. Additionally, we analyze the tumor cell response to antitumor treatment, heterogeneity of the tumor microenvironment, and response or resistance to immune checkpoint immunotherapy. The limitations of single-cell analysis in cancer research are also discussed. 

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High-throughput single-сell sequencing in cancer research

Single-cell RNA sequencing (scRNA-seq) has enabled us to study biological questions at the single-cell level. Currently, many analysis tools are available to better utilize these relatively noisy data. In this review, we summarize the most widely used methods for critical downstream analysis steps (i.e. clustering, trajectory inference, cell-type annotation and integrating datasets). The advantages and limitations are comprehensively discussed, and we provide suggestions for choosing proper methods in different situations. We hope this paper will be useful for scRNA-seq data analysts and bioinformatics tool developers.

Critical downstream analysis steps for single-cell RNA sequencing data.

Progress in structural biology research has led to a high demand for powerful and yet complementary analytical tools for structural characterization of proteins and protein complexes. This demand has significantly increased interest in native mass spectrometry (nMS), particularly native top-down mass spectrometry (nTDMS) in the past decade. This review highlights recent advances in nTDMS for structural research of biological assemblies, with a particular focus on the extra multi-layers of information enabled by TDMS. We include a short introduction of sample preparation and ionization to nMS, tandem fragmentation techniques as well as mass analyzers and software/analysis pipelines used for nTDMS. We highlight unique structural information offered by nTDMS and examples of its broad range of applications in proteins, protein-ligand interactions (metal, cofactor/drug, DNA/RNA, and protein), therapeutic antibodies and antigen-antibody complexes, membrane proteins, macromolecular machineries (ribosome, nucleosome, proteosome, and viruses), to endogenous protein complexes. The challenges, potential, along with perspectives of nTDMS methods for the analysis of proteins and protein assemblies in recombinant and biological samples are discussed.

Native top-down mass spectrometry for higher-order structural characterization of proteins and complexes.

With the development of artificial intelligence (AI) technologies and the availability of large amounts of biological data, computational methods for proteomics have undergone a developmental process from traditional machine learning to deep learning. This review focuses on computational approaches and tools for the prediction of protein–DNA/RNA interactions using machine intelligence techniques. We provide an overview of the development progress of computational methods and summarize the advantages and shortcomings of these methods. We further compiled applications in tasks related to the protein–DNA/RNA interactions, and pointed out possible future application trends. Moreover, biological sequence‐digitizing representation strategies used in different types of computational methods are also summarized and discussed.

Protein–DNA/RNA interactions: Machine intelligence tools and approaches in the era of artificial intelligence and big data


 With the rapid development of biotechnology, the number of biological sequences has grown exponentially. The continuous expansion of biological sequence data promotes the application of machine learning in biological sequences to construct predictive models for mining biological sequence information. There are many branches of biological sequence classification research. In this review, we mainly focus on the function and modification classification of biological sequences based on machine learning. Sequence-based prediction and analysis are the basic tasks to understand the biological functions of DNA, RNA, proteins, and peptides. However, there are hundreds of classification models developed for biological sequences, and the quite varied specific methods seem dizzying at first glance. Here, we aim to establish a long-term support website (
 http://lab.malab.cn/~acy/BioseqData/home.html
 ), which provides readers with detailed information on the classification method and download links to relevant datasets. We briefly introduce the steps to build an effective model framework for biological sequence data. In addition, a brief introduction to single-cell sequencing data analysis methods and applications in biology is also included. Finally, we discuss the current challenges and future perspectives of biological sequence classification research.


Biological Sequence Classification: A Review on Data and General Methods

Toward smarter management and recovery of municipal solid waste: A critical review on deep learning approaches

Single-cell RNA sequencing (scRNA-seq) has enabled researchers to study gene expression at the cellular level. However, due to the extremely low levels of transcripts in a single cell and technical losses during reverse transcription, gene expression at a single-cell resolution is usually noisy and highly dimensional; thus, statistical analyses of single-cell data are a challenge. Although many scRNA-seq data analysis tools are currently available, a gold standard pipeline is not available for all datasets. Therefore, a general understanding of bioinformatics and associated computational issues would facilitate the selection of appropriate tools for a given set of data. In this review, we provide an overview of the goals and most popular computational analysis tools for the quality control, normalization, imputation, feature selection and dimension reduction of scRNA-seq data.

Goals and approaches for each processing step for single-cell RNA sequencing data

SUMMARY
Integrative analysis of single-cell RNA-sequencing (scRNA-seq) data with spatial data for the same species and organ would provide each cell sample with a predictive spatial location, which would facilitate biological study. However, publicly available spatial sequencing datasets for specific species and organs are rare and are often displayed in different formats.In this study we introduce a new web-based scRNA-seq analysis tool, webSCST, that integrates well-organized spatial transcriptome sequencing datasets categorized by species and organs, provides a user-friendly interface for raw single-cell processing with popular integration methods, and allows users to submit their raw scRNA-seq data once to obtain predicted spatial locations for each cell type.


AVAILABILITY AND IMPLEMENTATION
webSCST implemented in shiny with all major browsers supported is available at http://www.webscst.com. webSCST is also freely available as an R package at https://github.com/swsoyee/webSCST.

Feifei Cui

Papers

Toward smarter management and recovery of municipal solid waste: A critical review on deep learning approaches

Goals and approaches for each processing step for single-cell RNA sequencing data

Critical downstream analysis steps for single-cell RNA sequencing data.

Protein–DNA/RNA interactions: Machine intelligence tools and approaches in the era of artificial intelligence and big data

webSCST: an interactive web application for single-cell RNA-sequencing data and spatial transcriptomic data integration