Molecular Systems Biology最新文献

Identifying T-cell clubs by embracing the local harmony between TCR and gene expressions. 通过 TCR 与基因表达之间的局部和谐来识别 T 细胞俱乐部。

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2024-11-04 DOI: 10.1038/s44320-024-00070-5

Yiping Zou, Jiaqi Luo, Lingxi Chen, Xueying Wang, Wei Liu, Ruo Han Wang, Shuai Cheng Li

{"title":"Identifying T-cell clubs by embracing the local harmony between TCR and gene expressions.","authors":"Yiping Zou, Jiaqi Luo, Lingxi Chen, Xueying Wang, Wei Liu, Ruo Han Wang, Shuai Cheng Li","doi":"10.1038/s44320-024-00070-5","DOIUrl":"10.1038/s44320-024-00070-5","url":null,"abstract":"T cell receptors (TCR) and gene expression provide two complementary and essential aspects in T cell understanding, yet their diversity presents challenges in integrative analysis. We introduce TCRclub, a novel method integrating single-cell RNA sequencing data and single-cell TCR sequencing data using local harmony to identify functionally similar T cell groups, termed 'clubs'. We applied TCRclub to 298,106 T cells across seven datasets encompassing various diseases. First, TCRclub outperforms the state-of-the-art methods in clustering T cells on a dataset with over 400 verified peptide-major histocompatibility complex categories. Second, TCRclub reveals a transition from activated to exhausted T cells in cholangiocarcinoma patients. Third, TCRclub discovered the pathways that could intervene in response to anti-PD-1 therapy for patients with basal cell carcinoma by analyzing the pre-treatment and post-treatment samples. Furthermore, TCRclub unveiled different T-cell responses and gene patterns at different severity levels in patients with COVID-19. Hence, TCRclub aids in developing more effective immunotherapeutic strategies for cancer and infectious diseases.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

XCMS-METLIN: data-driven metabolite, lipid, and chemical analysis. XCMS-METLIN：数据驱动的代谢物、脂质和化学分析。

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2024-11-01 Epub Date: 2024-09-19 DOI: 10.1038/s44320-024-00063-4

Martin Giera, Aries Aisporna, Winnie Uritboonthai, Linh Hoang, Rico J E Derks, Kara M Joseph, Erin S Baker, Gary Siuzdak

引用次数: 0

High-throughput protein characterization by complementation using DNA barcoded fragment libraries. 通过使用 DNA 条形码片段库进行互补，实现高通量蛋白质表征。

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2024-11-01 Epub Date: 2024-10-07 DOI: 10.1038/s44320-024-00068-z

Bradley W Biggs, Morgan N Price, Dexter Lai, Jasmine Escobedo, Yuridia Fortanel, Yolanda Y Huang, Kyoungmin Kim, Valentine V Trotter, Jennifer V Kuehl, Lauren M Lui, Romy Chakraborty, Adam M Deutschbauer, Adam P Arkin

{"title":"High-throughput protein characterization by complementation using DNA barcoded fragment libraries.","authors":"Bradley W Biggs, Morgan N Price, Dexter Lai, Jasmine Escobedo, Yuridia Fortanel, Yolanda Y Huang, Kyoungmin Kim, Valentine V Trotter, Jennifer V Kuehl, Lauren M Lui, Romy Chakraborty, Adam M Deutschbauer, Adam P Arkin","doi":"10.1038/s44320-024-00068-z","DOIUrl":"10.1038/s44320-024-00068-z","url":null,"abstract":"Our ability to predict, control, or design biological function is fundamentally limited by poorly annotated gene function. This can be particularly challenging in non-model systems. Accordingly, there is motivation for new high-throughput methods for accurate functional annotation. Here, we used complementation of auxotrophs and DNA barcode sequencing (Coaux-Seq) to enable high-throughput characterization of protein function. Fragment libraries from eleven genetically diverse bacteria were tested in twenty different auxotrophic strains of Escherichia coli to identify genes that complement missing biochemical activity. We recovered 41% of expected hits, with effectiveness ranging per source genome, and observed success even with distant E. coli relatives like Bacillus subtilis and Bacteroides thetaiotaomicron. Coaux-Seq provided the first experimental validation for 53 proteins, of which 11 are less than 40% identical to an experimentally characterized protein. Among the unexpected function identified was a sulfate uptake transporter, an O-succinylhomoserine sulfhydrylase for methionine synthesis, and an aminotransferase. We also identified instances of cross-feeding wherein protein overexpression and nearby non-auxotrophic strains enabled growth. Altogether, Coaux-Seq's utility is demonstrated, with future applications in ecology, health, and engineering.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction of a widespread bias in pooled chemical genomics screens improves their interpretability. 纠正集合化学基因组学筛选中的普遍偏差，提高其可解释性。

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2024-11-01 Epub Date: 2024-09-30 DOI: 10.1038/s44320-024-00069-y

Lili M Kim, Horia Todor, Carol A Gross

引用次数: 0

Author Correction: From coarse to fine: the absolute Escherichia coli proteome under diverse growth conditions. 作者更正：从粗到细：不同生长条件下大肠杆菌蛋白质组的绝对值。

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2024-11-01 DOI: 10.1038/s44320-024-00062-5

Matteo Mori, Zhongge Zhang, Amir Banaei-Esfahani, Jean-Benoît Lalanne, Hiroyuki Okano, Ben C Collins, Alexander Schmidt, Olga T Schubert, Deok-Sun Lee, Gene-Wei Li, Ruedi Aebersold, Terence Hwa, Christina Ludwig

引用次数: 0

Author Correction: Predictive evolution of metabolic phenotypes using model-designed environments. 作者更正：利用模型设计的环境预测代谢表型的进化。

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2024-11-01 DOI: 10.1038/s44320-024-00066-1

Paula Jouhten, Dimitrios Konstantinidis, Filipa Pereira, Sergej Andrejev, Kristina Grkovska, Sandra Castillo, Payam Ghiaci, Gemma Beltran, Eivind Almaas, Albert Mas, Jonas Warringer, Ramon Gonzalez, Pilar Morales, Kiran R Patil

引用次数: 0

Prediction of the 3D cancer genome from whole-genome sequencing using InfoHiC. 利用 InfoHiC 从全基因组测序预测三维癌症基因组。

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2024-11-01 Epub Date: 2024-09-25 DOI: 10.1038/s44320-024-00065-2

Yeonghun Lee, Sung-Hye Park, Hyunju Lee

{"title":"Prediction of the 3D cancer genome from whole-genome sequencing using InfoHiC.","authors":"Yeonghun Lee, Sung-Hye Park, Hyunju Lee","doi":"10.1038/s44320-024-00065-2","DOIUrl":"10.1038/s44320-024-00065-2","url":null,"abstract":"The 3D genome prediction in cancer is crucial for uncovering the impact of structural variations (SVs) on tumorigenesis, especially when they are present in noncoding regions. We present InfoHiC, a systemic framework for predicting the 3D cancer genome directly from whole-genome sequencing (WGS). InfoHiC utilizes contig-specific copy number encoding on the SV contig assembly, and performs a contig-to-total Hi-C conversion for the cancer Hi-C prediction from multiple SV contigs. We showed that InfoHiC can predict 3D genome folding from all types of SVs using breast cancer cell line data. We applied it to WGS data of patients with breast cancer and pediatric patients with medulloblastoma, and identified neo topologically associating domains. For breast cancer, we discovered super-enhancer hijacking events associated with oncogenic overexpression and poor survival outcomes. For medulloblastoma, we found SVs in noncoding regions that caused super-enhancer hijacking events of medulloblastoma driver genes (GFI1, GFI1B, and PRDM6). In addition, we provide trained models for cancer Hi-C prediction from WGS at https://github.com/dmcb-gist/InfoHiC , uncovering the impacts of SVs in cancer patients and revealing novel therapeutic targets.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteome-wide copy-number estimation from transcriptomics. 从转录组学估算整个蛋白质组的拷贝数

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2024-11-01 Epub Date: 2024-09-27 DOI: 10.1038/s44320-024-00064-3

Andrew J Sweatt, Cameron D Griffiths, Sarah M Groves, B Bishal Paudel, Lixin Wang, David F Kashatus, Kevin A Janes

{"title":"Proteome-wide copy-number estimation from transcriptomics.","authors":"Andrew J Sweatt, Cameron D Griffiths, Sarah M Groves, B Bishal Paudel, Lixin Wang, David F Kashatus, Kevin A Janes","doi":"10.1038/s44320-024-00064-3","DOIUrl":"10.1038/s44320-024-00064-3","url":null,"abstract":"Protein copy numbers constrain systems-level properties of regulatory networks, but proportional proteomic data remain scarce compared to RNA-seq. We related mRNA to protein statistically using best-available data from quantitative proteomics and transcriptomics for 4366 genes in 369 cell lines. The approach starts with a protein's median copy number and hierarchically appends mRNA-protein and mRNA-mRNA dependencies to define an optimal gene-specific model linking mRNAs to protein. For dozens of cell lines and primary samples, these protein inferences from mRNA outmatch stringent null models, a count-based protein-abundance repository, empirical mRNA-to-protein ratios, and a proteogenomic DREAM challenge winner. The optimal mRNA-to-protein relationships capture biological processes along with hundreds of known protein-protein complexes, suggesting mechanistic relationships. We use the method to identify a viral-receptor abundance threshold for coxsackievirus B3 susceptibility from 1489 systems-biology infection models parameterized by protein inference. When applied to 796 RNA-seq profiles of breast cancer, inferred copy-number estimates collectively re-classify 26-29% of luminal tumors. By adopting a gene-centered perspective of mRNA-protein covariation across different biological contexts, we achieve accuracies comparable to the technical reproducibility of contemporary proteomics.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep quantification of substrate turnover defines protease subsite cooperativity. 底物周转的深度定量确定了蛋白酶亚位点的合作性。

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2024-10-28 DOI: 10.1038/s44320-024-00071-4

Rajani Kanth Gudipati, Dimos Gaidatzis, Jan Seebacher, Sandra Muehlhaeusser, Georg Kempf, Simone Cavadini, Daniel Hess, Charlotte Soneson, Helge Großhans

{"title":"Deep quantification of substrate turnover defines protease subsite cooperativity.","authors":"Rajani Kanth Gudipati, Dimos Gaidatzis, Jan Seebacher, Sandra Muehlhaeusser, Georg Kempf, Simone Cavadini, Daniel Hess, Charlotte Soneson, Helge Großhans","doi":"10.1038/s44320-024-00071-4","DOIUrl":"https://doi.org/10.1038/s44320-024-00071-4","url":null,"abstract":"Substrate specificity determines protease functions in physiology and in clinical and biotechnological applications, yet quantitative cleavage information is often unavailable, biased, or limited to a small number of events. Here, we develop qPISA (quantitative Protease specificity Inference from Substrate Analysis) to study Dipeptidyl Peptidase Four (DPP4), a key regulator of blood glucose levels. We use mass spectrometry to quantify >40,000 peptides from a complex, commercially available peptide mixture. By analyzing changes in substrate levels quantitatively instead of focusing on qualitative product identification through a binary classifier, we can reveal cooperative interactions within DPP4's active pocket and derive a sequence motif that predicts activity quantitatively. qPISA distinguishes DPP4 from the related C. elegans DPF-3 (a DPP8/9-orthologue), and we relate the differences to the structural features of the two enzymes. We demonstrate that qPISA can direct protein engineering efforts like the stabilization of GLP-1, a key DPP4 substrate used in the treatment of diabetes and obesity. Thus, qPISA offers a versatile approach for profiling protease and especially exopeptidase specificity, facilitating insight into enzyme mechanisms and biotechnological and clinical applications.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bacterial live therapeutics for human diseases. 治疗人类疾病的活细菌疗法。

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2024-10-23 DOI: 10.1038/s44320-024-00067-0

Elisabet Frutos-Grilo, Yamile Ana, Javier Gonzalez-de Miguel, Marcel Cardona-I-Collado, Irene Rodriguez-Arce, Luis Serrano

引用次数: 0