Biophysics Reports

Online First

Articles in press have been peer-reviewed and accepted, which are not yet assigned to volumes/issues, but are citable by Digital Object Identifier (DOI).

METHOD

Tumor type classification and candidate cancer-specific biomarkers discovery via semi-supervised learning

Peng Chen, Zhenlei Li, Zhaolin Hong, Haoran Zheng, Rong Zeng

, Available online , doi: 10.52601/bpr.2023.230005

Abstract(31)

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Abstract:
Identifying cancer-related differentially expressed genes provides significant information for diagnosing tumors, predicting prognoses, and effective treatments. Recently, deep learning methods have been used to perform gene differential expression analysis using microarray-based high-throughput gene profiling and have achieved good results. In this study, we proposed a new robust multiple-datasets-based semi-supervised learning model, MSSL, to perform tumor type classification and candidate cancer-specific biomarkers discovery across multiple tumor types and multiple datasets, which addressed the following long-lasting obstacles: (1) the data volume of the existing single dataset is not enough to fully exert the advantages of deep learning; (2) a large number of datasets from different research institutions cannot be effectively used due to inconsistent internal variances and low quality; (3) relatively uncommon cancers have limited effects on deep learning methods. In our article, we applied MSSL to The Cancer Genome Atlas (TCGA) and the Gene Expression Comprehensive Database (GEO) pan-cancer normalized-level3 RNA-seq data and got 97.6% final classification accuracy, which had a significant performance leap compared with previous approaches. Finally, we got the ranking of the importance of the corresponding genes for each cancer type based on classification results and validated that the top genes selected in this way were biologically meaningful for corresponding tumors and some of them had been used as biomarkers, which showed the efficacy of our method.

MINI-REVIEW

Antioxidant activity of the thioredoxin system

Liu Zihua

, Available online , doi: 10.52601/bpr.2023.230002

Abstract(54)

PDF(2)

Abstract:
The thioredoxin system is composed of thioredoxin (Trx), thioredoxin reductase (TR) and reduced nicotinamide adenine dinucleotide phosphate. Trx is an important antioxidant molecule that can resist cell death caused by various stresses and plays a prominent role in redox reactions. TR is a protein that contains selenium (selenocysteine), in three main forms, namely, TR1, TR2 and TR3. TR1, TR2 and TR3 are mainly distributed in the cytoplasm, mitochondria, and testes, respectively. TR can regulate cell growth and apoptosis. After a cell becomes cancerous, the expression of TR is increased to promote cell growth and metastasis. The Trx system is closely related to neurodegenerative diseases, parasitic infections, acquired immunodeficiency syndrome, rheumatoid arthritis, hypertension, myocarditis, and so on. In addition, the Trx system can remove the reactive oxygen species in the body and keep the inside and outside of the cell in a balanced state. In summary, the Trx system is an important target for the drug treatment of many diseases.

RESEARCH ARTICLE

GNA12 regulates C5a-induced migration by downregulating C5aR1-PLCβ2-PI3K-AKT-ERK1/2 signaling

Yu Haonan, Liu Zhihua

, Available online , doi: 10.52601/bpr.2023.230001

Abstract(59)

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Abstract:
Gna12 has been identified as one of the reported inflammatory bowel disease (IBD) susceptibility genes in genome-wide association studies (GWAS). However, the function of GNA12 in intestinal homeostasis remains unknown. Here we report that GNA12, a G-protein α subunit, regulates C5a-induced migration in macrophages. Deficiency of GNA12 results in enhanced migration induced by C5a in macrophages. Mechanistically, GNA12 suppresses C5a-induced migration by downregulating the C5aR1-PLCβ2-PI3K-AKT-ERK1/2 signaling. Therefore, our study reveals that GNA12 is an anti-inflammatory factor, which might alleviate the development of inflammation by inhibiting the excessive chemotactic migration of macrophages.

IN MEMORIAM

Deep condolences to Professor Fuyu Yang

Editorial Board of Biophysics Reports

, Available online , doi: 10.52601/bpr.2023.230901

Abstract(141)

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Abstract:

PROTOCOL

Measurement of ATGL activity using adiposomes

Ma Xuejing, Zhi Zelun, Zhang Shuyan, Liu Pingsheng

, Available online , doi: 10.52601/bpr.2023.220016

Abstract(162)

PDF(16)

Abstract:
Adipose triacylglycerol lipase (ATGL) is a dynamic lipid droplet-associated protein involved in cellular lipolysis, which is conserved from bacteria to humans. Recent methods that measure the enzymatic activity of ATGL in vitro are established using lipid emulsions. However, the lipid emulsion platforms contain various membranous structures which reduce the accuracy of enzymatic activity determination. Therefore, a new platform and corresponding method are required for accurate measurement of ATGL enzymatic activity that represents cellular lipid and energy homeostasis. Adiposomes are artificial lipid nanostructures mimicking lipid droplets. Employing adiposome as a platform, we have developed an assay to measure the enzymatic activity of ATGL in vitro. Here, a detailed protocol is described to explain how to measure the activity of ATGL using adiposomes. This method successfully proves the concept of lipid droplet-mimetic lipase activity determining platform and provides a tool to identify the active sites of lipases.

Integrated proteomic and phosphoproteomic data-independent acquisition data evaluate the personalized drug responses of primary and metastatic tumors in colorectal cancer

Li Xumiao, Huang Yiming, Zheng Kuo, Yu Guanyu, Wang Qinqin, Gu Lei, Li Jingquan, Wang Hui, Zhang Wei, Sun Yidi, Li Chen

, Available online , doi: 10.52601/bpr.2022.210048

Abstract(237)

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Abstract:
Mass spectrometry (MS)-based proteomics and phosphoproteomics are powerful methods to study the biological mechanisms, diagnostic biomarkers, prognostic analysis, and drug therapy of tumors. Data-independent acquisition (DIA) mode is considered to perform better than data-dependent acquisition (DDA) mode in terms of quantitative reproducibility, specificity, accuracy, and identification of low-abundance proteins. Mini patient derived xenograft (MiniPDX) model is an effective model to assess the response to antineoplastic drugs in vivo and is helpful for the precise treatment of cancer patients. Kinases are favorable spots for tumor-targeted drugs, and their functional completion relies on signaling pathways through phosphorylating downstream substrates. Kinase-phosphorylation networks or edge interactions are considered more credible and permanent for characterizing complex diseases. Here, we provide a workflow for personalized drug response assessment in primary and metastatic colorectal cancer (CRC) tumors using DIA proteomic data, DIA phosphoproteomic data, and MiniPDX models. Three kinase inhibitors, afatinib, gefitinib, and regorafenib, are tested pharmacologically. The process mainly includes the following steps: clinical tissue collection, sample preparation, hybrid spectral libraries establishment, MS data acquisition, kinase-substrate network construction, in vivo drug test, and elastic regression modeling. Our protocol gives a more direct data basis for individual drug responses, and will improve the selection of treatment strategies for patients without the druggable mutation.

INVITED REVIEW

Multi-phase separation in mitochondrial nucleoids and eukaryotic nuclei

Long Qi, Zhou Yanshuang, Guo Jingyi, Wu Hao, Liu Xingguo

, Available online , doi: 10.52601/bpr.2023.220018

Abstract(126)

PDF(8)

Abstract:
In mammalian cells, besides nuclei, mitochondria are the only semi-autonomous organelles possessing own DNA organized in the form of nucleoids. While eukaryotic nuclear DNA compaction, chromatin compartmentalization and transcription are regulated by phase separation, our recent work proposed a model of mitochondrial nucleoid self-assembly and transcriptional regulation by multi-phase separation. Herein, we summarized the phase separation both in the nucleus and mitochondrial nucleoids, and did a comparison of the organization and activity regulating, which would provide new insight into the understanding of both architecture and genetics of nucleus and mitochondrial nucleoids.