Mammalian Genome最新文献_第5页

Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-02-12 DOI: 10.1007/s00335-025-10110-6

Sai Bhavani Gottumukkala, Anbumathi Palanisamy

{"title":"Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.","authors":"Sai Bhavani Gottumukkala, Anbumathi Palanisamy","doi":"10.1007/s00335-025-10110-6","DOIUrl":"https://doi.org/10.1007/s00335-025-10110-6","url":null,"abstract":"Non-Small Cell lung cancer (NSCLC) is known for its fast progression, metastatic potency, and a leading cause of mortality globally. At diagnosis, approximately 30-40% of NSCLC patients already present with metastasis. Epithelial to mesenchymal transition (EMT) is a developmental program implicated in cancer progression and metastasis. Transforming Growth Factor-β (TGFβ) and its signalling plays a prominent role in orchestrating the process of EMT and cancer metastasis. In present study, a comprehensive molecular interaction map of TGFβ induced EMT in NSCLC was developed through an extensive literature survey. The map encompasses 394 species interconnected through 554 reactions, representing the relationship and complex interplay between TGFβ induced SMAD dependent and independent signalling pathways (PI3K/Akt, Wnt, EGFR, JAK/STAT, p38 MAPK, NOTCH, Hypoxia). The map, built using Cell Designer and compliant with SBGN and SBML standards, was subsequently translated into a logical modelling framework using CaSQ and dynamically analysed with Cell Collective. These analyses illustrated the complex regulatory dynamics, capturing the known experimental outcomes of TGFβ induced EMT in NSCLC including the co-existence of hybrid EM phenotype during transition. Hybrid EM phenotype is known to contribute for the phenotypic plasticity during metastasis. Network-based analysis identified the crucial network level properties and hub regulators, while the transcriptome-based analysis cross validated the prognostic significance and clinical relevance of key regulators. Overall, the map developed and the subsequent analyses offer deeper understanding of the complex regulatory network governing the process of EMT in NSCLC.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Correction: Canine models of inherited retinal diseases: from neglect to well-recognized translational value.

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-02-11 DOI: 10.1007/s00335-025-10108-0

Valérie L Dufour, Gustavo D Aguirre

引用次数: 0

CTNNB1 syndrome mouse models. CTNNB1综合征小鼠模型。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-01-20 DOI: 10.1007/s00335-025-10105-3

Duško Lainšček, Vida Forstnerič, Špela Miroševič

{"title":"CTNNB1 syndrome mouse models.","authors":"Duško Lainšček, Vida Forstnerič, Špela Miroševič","doi":"10.1007/s00335-025-10105-3","DOIUrl":"https://doi.org/10.1007/s00335-025-10105-3","url":null,"abstract":"CTNNB1 syndrome is a rare neurodevelopmental disorder, affecting children worldwide with a prevalence of 2.6-3.2 per 100,000 births and often misdiagnosed as cerebral palsy. De novo loss-of-function mutations in the Ctnnb1 gene result in dysfunction of the β-catenin protein, disrupting the canonical Wnt signaling pathway, which plays a key role in cell proliferation, differentiation, and tissue homeostasis. Additionally, these mutations impair the formation of cell junctions, adversely affecting tissue architecture. Motor and speech deficits, cognitive impairment, cardiovascular and visual problems are just some of the key symptoms that occur in CTNNB1 syndrome patients. There is currently no effective treatment option available for patients with CTNNB1 syndrome, with support largely focused on the management of symptoms and physiotherapy, yet recently some therapeutic approaches are being developed. Animal testing is still crucial in the process of new drug development, and mouse models are particularly important. These models provide researchers with new understanding of the disease mechanisms and are invaluable for testing the efficacy and safety of potential treatments. The development of various mouse models with β-catenin loss- and gain-of-function mutations successfully replicates key features of intellectual disability, autism-like behaviors, motor deficits, and more. These models provide a valuable platform for studying disease mechanisms and offer a powerful tool for testing the therapeutic potential and effectiveness of new drug candidates, paving the way for future clinical trials.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

IMPC impact on preclinical mouse models. IMPC对临床前小鼠模型的影响。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-01-16 DOI: 10.1007/s00335-025-10104-4

Sabine M Hölter, Pilar Cacheiro, Damian Smedley, K C Kent Lloyd

引用次数: 0

Genome engineering with Cas9 and AAV repair templates, successes and pitfalls. 基因组工程与Cas9和AAV修复模板，成功与缺陷。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-01-13 DOI: 10.1007/s00335-024-10099-4

M C Birling, Y Hérault, G Pavlovic

引用次数: 0

Understanding PACS2 syndrome's pathomechanism by studying E209K and E211K mutations. 通过研究E209K和E211K突变了解PACS2综合征的发病机制。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-12-30 DOI: 10.1007/s00335-024-10098-5

Arkadiusz Zbikowski, Tomasz Kowalczyk, Petr Kasparek, Jan Prohazka, Radislav Sedlacek, Michał Ciborowski, Dominik Cysewski, Kacper Łukasiewicz

{"title":"Understanding PACS2 syndrome's pathomechanism by studying E209K and E211K mutations.","authors":"Arkadiusz Zbikowski, Tomasz Kowalczyk, Petr Kasparek, Jan Prohazka, Radislav Sedlacek, Michał Ciborowski, Dominik Cysewski, Kacper Łukasiewicz","doi":"10.1007/s00335-024-10098-5","DOIUrl":"https://doi.org/10.1007/s00335-024-10098-5","url":null,"abstract":"Phosphofurin acidic cluster sorting protein 2 (PACS2) plays a vital role in maintaining cellular homeostasis by regulating protein trafficking between cellular membranes. This function impacts crucial processes like apoptosis, mitochondria-endoplasmic reticulum interaction, and subsequently Ca2+ flux, lipid biosynthesis, and autophagy. Missense mutations, particularly E209K and E211K, are linked to developmental and epileptic encephalopathy-66 (DEE66), known as PACS2 syndrome. Individuals with this syndrome exhibit neurodevelopmental delay, seizures, facial dysmorphism, hypotonia, and delayed motor skills.Understanding the impact of these missense mutations on molecular processes is crucial. Studies suggest that E209K mutation decreases phosphorylation, increases the survival time of protein, and modifies protein-protein interaction, consequently leading to disruption of calcium flux and lower resistance to apoptosis induction. Unfortunately, to date, only a limited number of research groups have investigated the effects of mutations in the PACS2 gene. Current research on PACS2 syndrome is hampered by the lack of suitable models. While in vitro models using transfected cell lines offer insights, they cannot fully capture the disease's complexity.To address this, utilizing cells from individuals with PACS2 syndrome, specifically induced pluripotent stem cells (iPSCs), holds promise for understanding phenotypic diversity and developing personalized therapies. However, iPSC models may not fully capture tissue-specific effects of the E209K/E211K mutation. In vivo studies using animal models, particularly mice, could overcome these limitations.This review summarizes current knowledge about PACS2 structure and functions, explores the cellular consequences of E209K and E211K mutations, and highlights the potential of iPSC and mouse models in advancing our understanding of PACS2 syndrome.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Canine models of inherited retinal diseases: from neglect to well-recognized translational value. 遗传性视网膜疾病的犬模型：从被忽视到公认的转化价值。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-12-30 DOI: 10.1007/s00335-024-10091-y

Valérie L Dufour, Gustavo D Aguirre

引用次数: 0

Identification of prostate cancer associated genes for diagnosis and prognosis: a modernized in silico approach. 用于诊断和预后的前列腺癌相关基因鉴定：一种现代化的硅学方法。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-12-01 Epub Date: 2024-08-17 DOI: 10.1007/s00335-024-10060-5

Akilandeswari Ramu, Lekhashree Ak, Jayaprakash Chinnappan

{"title":"Identification of prostate cancer associated genes for diagnosis and prognosis: a modernized in silico approach.","authors":"Akilandeswari Ramu, Lekhashree Ak, Jayaprakash Chinnappan","doi":"10.1007/s00335-024-10060-5","DOIUrl":"10.1007/s00335-024-10060-5","url":null,"abstract":"Prostate cancer (PCa) ranks as the second leading cause of cancer-related deaths in men. Diagnosing PCa relies on molecular markers known as diagnostic biomarkers, while prognostic biomarkers are used to identify key proteins involved in PCa treatments. This study aims to gather PCa-associated genes and assess their potential as either diagnostic or prognostic biomarkers for PCa. A corpus of 152,064 PCa-related data from PubMed, spanning from May 1936 to December 2020, was compiled. Additionally, 4199 genes associated with PCa terms were collected from the National Center of Biotechnology Information (NCBI) database. The PubMed corpus data was extracted using pubmed.mineR to identify PCa-associated genes. Network and pathway analyses were conducted using various tools, such as STRING, DAVID, KEGG, MCODE 2.0, cytoHubba app, CluePedia, and ClueGO app. Significant marker genes were identified using Random Forest, Support Vector Machines, Neural Network algorithms, and the Cox Proportional Hazard model. This study reports 3062 unique PCa-associated genes along with 2518 corresponding unique PMIDs. Diagnostic markers such as IL6, MAPK3, JUN, FOS, ACTB, MYC, and TGFB1 were identified, while prognostic markers like ACTB and HDAC1 were highlighted in PubMed. This suggests that the potential target genes provided by PubMed data outweigh those in the NCBI database.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"683-710"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Diverse wild-derived inbred strains provide a new community resource. 多样化的野生近交系提供了新的社区资源。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-12-01 Epub Date: 2024-08-19 DOI: 10.1007/s00335-024-10061-4

Michael W Nachman, Beth L Dumont

引用次数: 0

A graph theoretical approach to experimental prioritization in genome-scale investigations. 基因组规模研究中确定实验优先次序的图论方法。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-12-01 Epub Date: 2024-08-27 DOI: 10.1007/s00335-024-10066-z

Stephen K Grady, Kevin A Peterson, Stephen A Murray, Erich J Baker, Michael A Langston, Elissa J Chesler

{"title":"A graph theoretical approach to experimental prioritization in genome-scale investigations.","authors":"Stephen K Grady, Kevin A Peterson, Stephen A Murray, Erich J Baker, Michael A Langston, Elissa J Chesler","doi":"10.1007/s00335-024-10066-z","DOIUrl":"10.1007/s00335-024-10066-z","url":null,"abstract":"The goal of systems biology is to gain a network level understanding of how gene interactions influence biological states, and ultimately inform upon human disease. Given the scale and scope of systems biology studies, resource constraints often limit researchers when validating genome-wide phenomena and potentially lead to an incomplete understanding of the underlying mechanisms. Further, prioritization strategies are often biased towards known entities (e.g. previously studied genes/proteins with commercially available reagents), and other technical issues that limit experimental breadth. Here, heterogeneous biological information is modeled as an association graph to which a high-performance minimum dominating set solver is applied to maximize coverage across the graph, and thus increase the breadth of experimentation. First, we tested our model on retrieval of existing gene functional annotations and demonstrated that minimum dominating set returns more diverse terms when compared to other computational methods. Next, we utilized our heterogenous network and minimum dominating set solver to assist in the process of identifying understudied genes to be interrogated by the International Mouse Phenotyping Consortium. Using an unbiased algorithmic strategy, poorly studied genes are prioritized from the remaining thousands of genes yet to be characterized. This method is tunable and extensible with the potential to incorporate additional user-defined prioritizing information. The minimum dominating set approach can be applied to any biological network in order to identify a tractable subset of features to test experimentally or to assist in prioritizing candidate genes associated with human disease.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"724-733"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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