bioRxiv - Systems Biology最新文献_第3页

AxonFinder: Automated segmentation of tumor innervating neuronal fibers AxonFinder：自动分割肿瘤支配神经元纤维

bioRxiv - Systems Biology Pub Date : 2024-09-07 DOI: 10.1101/2024.09.03.611089

Kaoutar Ait-Ahmad, Cigdem Ak, Guillaume Thibault, Young Hwan Chang, Sebnem Ece Eksi

{"title":"AxonFinder: Automated segmentation of tumor innervating neuronal fibers","authors":"Kaoutar Ait-Ahmad, Cigdem Ak, Guillaume Thibault, Young Hwan Chang, Sebnem Ece Eksi","doi":"10.1101/2024.09.03.611089","DOIUrl":"https://doi.org/10.1101/2024.09.03.611089","url":null,"abstract":"Neurosignaling is increasingly recognized as a critical factor in cancer progression, where neuronal innervation of primary tumors contributes to the disease's advancement. This study focuses on segmenting individual axons within the prostate tumor microenvironment, which have been challenging to detect and analyze due to their irregular morphologies. We present a novel deep learning-based approach for the automated segmentation of axons, AxonFinder, leveraging a U-Net model with a ResNet-101 encoder, based on a multiplexed imaging approach. Utilizing a dataset of whole-slide images from low-, intermediate-, and high-risk prostate cancer patients, we manually annotated axons to train our model, achieving significant accuracy in detecting axonal structures that were previously hard to segment. Our analysis includes a comprehensive assessment of axon density and morphological features across different CAPRA-S prostate cancer risk categories, providing insights into the correlation between tumor innervation and cancer progression. Our paper suggests the potential utility of neuronal markers in the prognostic assessment of prostate cancer in aiding the pathologist's assessment of tumor sections and advancing our understanding of neurosignaling in the tumor microenvironment.","PeriodicalId":501213,"journal":{"name":"bioRxiv - Systems Biology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of Chronotypes Using the Symbolic Aggregate approXimation (SAX) on Actigraphy Data 使用符号聚合法 (SAX) 分析行动记录仪数据的时间型特征

bioRxiv - Systems Biology Pub Date : 2024-09-06 DOI: 10.1101/2024.09.03.611014

Wen Luo, Ioannis P Androulakis

{"title":"Characterization of Chronotypes Using the Symbolic Aggregate approXimation (SAX) on Actigraphy Data","authors":"Wen Luo, Ioannis P Androulakis","doi":"10.1101/2024.09.03.611014","DOIUrl":"https://doi.org/10.1101/2024.09.03.611014","url":null,"abstract":"This study discusses an efficient approach to characterizing chronotypes using Symbolic Aggregate approXimation (SAX) on actigraphy data. Actigraphy, a non-invasive monitoring of human rest/activity cycles, provides valuable insights into sleep-wake behaviors and circadian rhythms. However, the high dimensionality of actigraphy data poses significant challenges in storage, processing, and analysis. To address these challenges, we applied the SAX algorithm to transform continuous time-series actigraphy data into a symbolic representation, enabling dimensionality reduction while preserving essential patterns. We analyzed actigraphy data from the National Health and Nutrition Examination Survey (NHANES) database, covering over 10,000 individuals, and used unsupervised clustering to identify distinct chronotype patterns. The SAX transformation facilitated the application of machine learning techniques, revealing five chronotype clusters characterized by differences in activity onset, resolution, and intensity. Age distribution analysis showed biases towards specific age groups within the clusters, highlighting the relationship between age and chronotype. Key findings include age-related Chronotype variations with younger individuals exhibiting delayed chronotypes with significant differences in sleep onset (SOT) and wake time (WT) compared to older adults, suggesting a phase delay in sleep patterns as age decreases and activity transition dynamics where clusters showed distinct patterns in winding up and winding down periods, providing insights into the dynamics of activity transitions. This study demonstrates the efficiency and effectiveness of SAX in processing large-scale actigraphy data, enabling robust chronotype characterization that can inform personalized healthcare and public health initiatives. Further exploration of SAX integration with other biometric measures could deepen our understanding of human circadian biology and its impact on health and behavior.","PeriodicalId":501213,"journal":{"name":"bioRxiv - Systems Biology","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A statistical-based method for the construction and analysis of gene network：application to bacteria 基于统计的基因网络构建与分析方法：在细菌中的应用

bioRxiv - Systems Biology Pub Date : 2024-09-06 DOI: 10.1101/2024.09.03.611021

Zhiyuan Zhang, Guozhong Chen, Erguang Li

{"title":"A statistical-based method for the construction and analysis of gene network：application to bacteria","authors":"Zhiyuan Zhang, Guozhong Chen, Erguang Li","doi":"10.1101/2024.09.03.611021","DOIUrl":"https://doi.org/10.1101/2024.09.03.611021","url":null,"abstract":"Bacteria play a crucial role in environmental conservation, human health, and medicine. Whether in the gut or the soil, bacterial genomes are rich repositories of resources, such as exploring potential drugs and biopesticides. However, our ability to develop new therapies and deepen our understanding of the bacterial world is hindered by the largely unknown functions of bacterial genes. In this study, we proposed a method of gene network construction and analysis based on a Gaussian Graphical Model (GGM) and random sampling strategy to infer direct interactions at the genomic level in bacteria. Using Vibrio cholerae and Staphylococcus aureus as examples, we integrated partial correlation-based gene co-expression data with gene regulatory and essentiality information extracted from public databases to construct more comprehensive gene networks. Networks built upon bacterial different phenotypes, such as biofilm formation, flagellar assembly, and stress response, demonstrate the effectiveness of this method in deciphering unknown gene functions, uncovering new phenotype-associated factors, and identifying their corresponding interactions, thus providing new targets for experimental validation by researchers. Additionally, we extended this method to 14 bacteria, including 13 pathogens, supporting the investigation of gene functions and pathways at the genomic level in these bacteria. More importantly, for other species, this method of gene network construction can be easily implemented, provided that sufficient transcriptome sequencing samples are available.","PeriodicalId":501213,"journal":{"name":"bioRxiv - Systems Biology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Abundant clock proteins point to missing molecular regulation in the plant circadian clock 丰富的时钟蛋白表明植物昼夜节律时钟的分子调控功能缺失

bioRxiv - Systems Biology Pub Date : 2024-09-03 DOI: 10.1101/2024.09.03.609973

Uriel Urquiza-Garcia, Nacho Molina, Karen J. Halliday, Andrew J Millar

{"title":"Abundant clock proteins point to missing molecular regulation in the plant circadian clock","authors":"Uriel Urquiza-Garcia, Nacho Molina, Karen J. Halliday, Andrew J Millar","doi":"10.1101/2024.09.03.609973","DOIUrl":"https://doi.org/10.1101/2024.09.03.609973","url":null,"abstract":"Understanding the biochemistry behind whole-organism traits such as flowering time is a longstanding challenge, where mathematical models are critical. Very few models of plant gene circuits use the absolute units required for comparison to biochemical data. We refactor two detailed models of the plant circadian clock from relative to absolute units. Using absolute RNA quantification, a simple model predicted abundant clock protein levels in Arabidopsis thaliana, up to 100,000 proteins per cell. NanoLUC reporter protein fusions validated the predicted levels of clock proteins in vivo. Recalibrating the detailed models to these protein levels estimated their DNA-binding dissociation constants (Kd). We estimate the same Kd from multiple results in vitro, extending the method to any promoter sequence. The detailed models simulated the Kd range estimated from LUX DNA-binding in vitro but departed from the data for CCA1 binding, pointing to further circadian mechanisms. Our analytical and experimental methods should transfer to understand other plant gene regulatory networks, potentially including the natural sequence variation that contributes to evolutionary adaptation.","PeriodicalId":501213,"journal":{"name":"bioRxiv - Systems Biology","volume":"106 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantitative modelling of fate speciﬁcation in the C. elegans postembryonic M lineage reveals a missing spatiotemporal signal 对 elegans 胚后 M 系命运分化的定量建模揭示了一个缺失的时空信号

bioRxiv - Systems Biology Pub Date : 2024-09-03 DOI: 10.1101/2024.09.01.610667

Benjamin Planterose Jiménez, Alexander R Blackwell, João J Ramalho, Sander van den Heuvel, Kirsten ten Tusscher, Erika Tsingos

{"title":"Quantitative modelling of fate speciﬁcation in the C. elegans postembryonic M lineage reveals a missing spatiotemporal signal","authors":"Benjamin Planterose Jiménez, Alexander R Blackwell, João J Ramalho, Sander van den Heuvel, Kirsten ten Tusscher, Erika Tsingos","doi":"10.1101/2024.09.01.610667","DOIUrl":"https://doi.org/10.1101/2024.09.01.610667","url":null,"abstract":"The invariant lineages of C. elegans provide tractable cell fate models to study how developing organisms robustly integrate spatial signals at the single-cell level via gene regulatory networks. For instance, during postembryonic development, a mesoderm lineage arises through a sequence of oriented cell divisions from a single progenitor. This mesoblast initially gives rise to 18 cells with three distinct fates – 14 body wall muscles (BWMs), 2 coelomocytes (CCs; dorsal), and 2 sex myoblasts (SMs; ventral). The latter cells migrate and then proliferate to contribute 16 smooth muscles to the nematode's reproductive organs. Prior work identified key symmetry breaking cues: i) ventrally restricted activation of the LIN-12 Notch pathway promoting SM over CC fate and ii) asymmetric re-distribution of SYS-1 β-catenin and POP-1 TCF among daughter cells along the anteroposterior (A-P) axis, i.e. the Wnt/β-catenin asymmetry pathway. However, it remains unclear whether these pathways are sufficient to specify all cell fates accordingly or whether additional symmetry breaking cues are necessary. In this study, we use quantitative modelling to better understand fate specification in the postembryonic M lineage. Specifically, we focus on the anteroposterior symmetry break by creating increasingly complex models towards robustly reproducing fate specification in wild type larvae and mutants. This iterative process resulted in two alternative models that explain the experimental observations by either introducing an additional spatial (spatial symmetry break) or temporal cue (temporal symmetry break). Finally, we evaluate their plausibility and propose a series of experiments to provide support for alternative models. Overall, our study highlights how a quantitative examination of mechanistic ideas can identify knowledge gaps and guide experimental follow-up.","PeriodicalId":501213,"journal":{"name":"bioRxiv - Systems Biology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Water-saving GC-MC model captures temporally differential enzymatic and transporter activities during C3-CAM transition 节水型 GC-MC 模型捕捉到 C3-CAM 转换过程中酶和转运体活动的时间差异

bioRxiv - Systems Biology Pub Date : 2024-09-03 DOI: 10.1101/2024.09.02.610818

Devlina Sarkar, Sudip Kundu

{"title":"Water-saving GC-MC model captures temporally differential enzymatic and transporter activities during C3-CAM transition","authors":"Devlina Sarkar, Sudip Kundu","doi":"10.1101/2024.09.02.610818","DOIUrl":"https://doi.org/10.1101/2024.09.02.610818","url":null,"abstract":"CAM (Crassulacean Acid Metabolism) plants reduce the water loss through transpiration in arid environments (Wickell et al., 2021), using an alternative pathway of carbon assimilation. To ensure food security, engineering CAM into C3 plants can be achieved by inverting the stomatal rhythm and the timing of major CO2 uptake from day to night. Identification of the metabolic enzymes and intra-cellular transporters, present in both C3 and CAM but having different differential temporal activities throughout the diel cycle (Yang et al., 2015; Heyduk et al., 2019) and quantitative estimations of the flux distributions along the biochemical trajectory of C3-to-CAM transition may help us to achieve the goal. Here, we simulate a constraint-based combined metabolic model of guard cell (GC) and mesophyll cell (MC), linking temporal fluctuations of temperature (T) and relative humidity (RH) throughout the diurnal cycle with osmolyte accumulation dependent stomatal opening, CO2 uptake and transpirational water loss. Starting with C3 metabolism, gradual increase in water-use efficiency (WUE) captures several known and new differential activities of metabolic enzymes, transporters, sugar-malate cycle etc. in GC and MC during C3-to-CAM transition.","PeriodicalId":501213,"journal":{"name":"bioRxiv - Systems Biology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exchange, promiscuity, and orthogonality in de novo designed coiled-coil peptide assemblies 全新设计的盘绕肽组装中的交换、杂交和正交性

bioRxiv - Systems Biology Pub Date : 2024-09-02 DOI: 10.1101/2024.09.01.610678

Kathleen Wilson Kurgan, Freddie James Oliver Martin, William Michael Dawson, Thomas Brunnock, Andrew J Orr-Ewing, Dek N Woolfson

{"title":"Exchange, promiscuity, and orthogonality in de novo designed coiled-coil peptide assemblies","authors":"Kathleen Wilson Kurgan, Freddie James Oliver Martin, William Michael Dawson, Thomas Brunnock, Andrew J Orr-Ewing, Dek N Woolfson","doi":"10.1101/2024.09.01.610678","DOIUrl":"https://doi.org/10.1101/2024.09.01.610678","url":null,"abstract":"De novo protein design is delivering new peptide and protein structures at a rapid pace. Many of these synthetic polypeptides form well-defined and hyperthermal-stable structures. Generally, however, less is known about the dynamic properties of the de novo designed structures. Here, we explore one aspect of dynamics in a series of de novo coiled-coil peptide assemblies: namely, peptide exchange within and between different oligomers from dimers through to heptamers. First, we develop a fluorescence-based reporter assay for peptide exchange that is straightforward to implement, and, thus, would be useful to others examining similar systems. We apply this assay to explore both homotypic exchange within single species, and heterotypic exchange between coiled coils of different coiled-coil oligomer states. For the former, we provide detailed study for the dimeric coiled coil CC-Di finding a half-life for exchange of 4.2 plus or minus 0.3 minutes when the concentration of CC-Di is 200 micro molar. Interestingly, more broadly when assessing exchange across all of the oligomeric states, we find that some of the designs are faithful and only undergo homotypic strand exchange, whereas others are promiscuous and exchange to form unexpected hetero-oligomers. Finally, we develop two design strategies to improve the orthogonality of the different oligomers: (i) using alternate positioning of salt bridge interactions; and (ii) incorporating of non-canonical repeats into the designed sequences. In so doing, we reconcile the promiscuity and deliver a set of faithful homo-oligomeric de novo coiled-coil peptides. Our findings have implications for the application of these and other coiled coils as modules in chemical and synthetic biology.","PeriodicalId":501213,"journal":{"name":"bioRxiv - Systems Biology","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dissecting reversible and irreversible single cell state transitions from gene regulatory networks 从基因调控网络剖析可逆和不可逆的单细胞状态转换

bioRxiv - Systems Biology Pub Date : 2024-09-01 DOI: 10.1101/2024.08.30.610498

Daniel Ramirez, Mingyang Lu

引用次数: 0

Emergent metabolic interactions in resistance to Clostridioides difficile invasion 抵御艰难梭状芽孢杆菌入侵的新陈代谢相互作用

bioRxiv - Systems Biology Pub Date : 2024-08-30 DOI: 10.1101/2024.08.29.610284

Achuthan Ambat, Naomi Iris van den Berg, Francisco Zorrilla, Shruti Menon, Abhijit Maji, Arianna Basile, Sudeep Ghimire, Lajos Kalmar, Kiran Raosaheb Patil, Joy Scaria

{"title":"Emergent metabolic interactions in resistance to Clostridioides difficile invasion","authors":"Achuthan Ambat, Naomi Iris van den Berg, Francisco Zorrilla, Shruti Menon, Abhijit Maji, Arianna Basile, Sudeep Ghimire, Lajos Kalmar, Kiran Raosaheb Patil, Joy Scaria","doi":"10.1101/2024.08.29.610284","DOIUrl":"https://doi.org/10.1101/2024.08.29.610284","url":null,"abstract":"Commensal gut bacteria are key contributors to the resilience against pathogen invasion. This is exemplified by the success of fecal microbiota transplantation in treating recurrent Clostridioides difficile infection. Yet, characteristics of communities that can confer colonization resistance and the underlying mechanisms remain largely unknown. Here we use a synthetic community of 14 commensal gut bacteria to uncover inter-species interactions and metabolic pathways underpinning the emergent resilience against C. difficile invasion. We challenged this synthetic community as well as fecal-matter-derived communities with antibiotic treatment and C. difficile in a continuous flow bioreactor. Using generalized Lotka-Volterra and genome-scale metabolic modelling, we identified interactions between Escherichia coli and Bacteroides/Phocaeicola sp. as key to the pathogen's suppression. Metabolomics analysis further revealed that fructooligosaccharide metabolism, vitamin B3 biosynthesis, and competition for Stickland metabolism precursors contribute to suppression. Analysis of metagenomics data from patient cohorts and clinical trials attested the in vivo relevance of the identified metabolic pathways and the ratio between Bacteroides and Escherichia in successful colonization resistance. The latter was found to be a much stronger discriminator than commonly used alpha diversity metrics. Our study uncovers emergent microbial interactions in pathogen resistance with implications for rational design of bacteriotherapies.","PeriodicalId":501213,"journal":{"name":"bioRxiv - Systems Biology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prediction and principle discovery of drug combination based on multimodal friendship features 基于多模态友谊特征的药物组合预测和原理发现

bioRxiv - Systems Biology Pub Date : 2024-08-30 DOI: 10.1101/2024.08.28.610203

He-Gang Chen, XIONGHUI ZHOU

{"title":"Prediction and principle discovery of drug combination based on multimodal friendship features","authors":"He-Gang Chen, XIONGHUI ZHOU","doi":"10.1101/2024.08.28.610203","DOIUrl":"https://doi.org/10.1101/2024.08.28.610203","url":null,"abstract":"Combination therapy, which can improve therapeutic efficacy and reduce side effects, plays an important role in the treatment of multiple complex diseases. Yet, the design principles of molecular combinations remain unclear. In addition, the huge search space of candidate drug combinations and the numerous heterogeneous data has brought us a big challenge. Here, we proposed a Friendship based Method (FSM), which integrates diverse drug-to-drug information to predict drug combinations for specific diseases. By quantifying the friendship-based relationship between drugs, we found that there is a moderate similarity between the drugs of effective drug combinations in a high-dimensional, heterogeneous feature space. Following this discovery, FSM applied a two-step strategy to predict clinically efficacious drug combinations for specific diseases. First, our method employs the friendship features to evaluate whether each drug is combinable. Then, the synergistic potential of combinable drugs was further evaluated. FSM was validated on two types of disease. The results show that FSM achieves substantial performance improvement over other state-of-the-art methods and tends to have low toxicity. These results indicate that our model could potentially offer a generic, powerful strategy to identify efficacious combination therapies in the vast search space.","PeriodicalId":501213,"journal":{"name":"bioRxiv - Systems Biology","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0