Life Science Alliance最新文献_第7页

NeoMUST: an accurate and efficient multi-task learning model for neoantigen presentation. NeoMUST：准确高效的新抗原呈现多任务学习模型。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-30 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302255

Wang Ma, Jiawei Zhang, Hui Yao

引用次数: 0

Mapping parental DMRs predictive of local and distal methylome remodeling in epigenetic F1 hybrids. 绘制可预测表观遗传 F1 杂交种局部和远端甲基组重塑的亲本 DMRs 图。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-30 Print Date: 2024-04-01 DOI: 10.26508/lsa.202402599

Ioanna Kakoulidou, Robert S Piecyk, Rhonda C Meyer, Markus Kuhlmann, Caroline Gutjahr, Thomas Altmann, Frank Johannes

{"title":"Mapping parental DMRs predictive of local and distal methylome remodeling in epigenetic F1 hybrids.","authors":"Ioanna Kakoulidou, Robert S Piecyk, Rhonda C Meyer, Markus Kuhlmann, Caroline Gutjahr, Thomas Altmann, Frank Johannes","doi":"10.26508/lsa.202402599","DOIUrl":"10.26508/lsa.202402599","url":null,"abstract":"F1 hybrids derived from a cross between two inbred parental lines often display widespread changes in DNA methylation and gene expression patterns relative to their parents. An emerging challenge is to understand how parental epigenomic differences contribute to these events. Here, we generated a large mapping panel of F1 epigenetic hybrids, whose parents are isogenic but variable in their DNA methylation patterns. Using a combination of multi-omic profiling and epigenetic mapping strategies we show that differentially methylated regions in parental pericentromeres act as major reorganizers of hybrid methylomes and transcriptomes, even in the absence of genetic variation. These parental differentially methylated regions are associated with hybrid methylation remodeling events at thousands of target regions throughout the genome, both locally (in cis) and distally (in trans). Many of these distally-induced methylation changes lead to nonadditive expression of nearby genes and associate with phenotypic heterosis. Our study highlights the pleiotropic potential of parental pericentromeres in the functional remodeling of hybrid genomes and phenotypes.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Integrated analysis of RNA-seq datasets reveals novel targets and regulators of COVID-19 severity. RNA-seq数据集的综合分析揭示了COVID-19严重程度的新靶标和调节因子。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-23 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302358

Thais Teixeira Oliveira, Júlia Firme Freitas, Viviane Priscila Barros de Medeiros, Thiago Jesus da Silva Xavier, Lucymara Fassarella Agnez-Lima

{"title":"Integrated analysis of RNA-seq datasets reveals novel targets and regulators of COVID-19 severity.","authors":"Thais Teixeira Oliveira, Júlia Firme Freitas, Viviane Priscila Barros de Medeiros, Thiago Jesus da Silva Xavier, Lucymara Fassarella Agnez-Lima","doi":"10.26508/lsa.202302358","DOIUrl":"10.26508/lsa.202302358","url":null,"abstract":"During the COVID-19 pandemic, RNA-seq datasets were produced to investigate the virus-host relationship. However, much of these data remains underexplored. To improve the search for molecular targets and biomarkers, we performed an integrated analysis of multiple RNA-seq datasets, expanding the cohort and including patients from different countries, encompassing severe and mild COVID-19 patients. Our analysis revealed that severe COVID-19 patients exhibit overexpression of genes coding for proteins of extracellular exosomes, endomembrane system, and neutrophil granules (e.g., S100A9, LY96, and RAB1B), which may play an essential role in the cellular response to infection. Concurrently, these patients exhibit down-regulation of genes encoding components of the T cell receptor complex and nucleolus, including TP53, IL2RB, and NCL Finally, SPI1 may emerge as a central transcriptional factor associated with the up-regulated genes, whereas TP53, MYC, and MAX were associated with the down-regulated genes during COVID-19. This study identified targets and transcriptional factors, lighting on the molecular pathophysiology of syndrome coronavirus 2 infection.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10806258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Drosophila MIC10b can polymerize into cristae-shaping filaments. 果蝇的 MIC10b 可以聚合成嵴状细丝。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-22 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302177

Till Stephan, Stefan Stoldt, Mariam Barbot, Travis D Carney, Felix Lange, Mark Bates, Peter Bou Dib, Kaushik Inamdar, Halyna R Shcherbata, Michael Meinecke, Dietmar Riedel, Sven Dennerlein, Peter Rehling, Stefan Jakobs

{"title":"Drosophila MIC10b can polymerize into cristae-shaping filaments.","authors":"Till Stephan, Stefan Stoldt, Mariam Barbot, Travis D Carney, Felix Lange, Mark Bates, Peter Bou Dib, Kaushik Inamdar, Halyna R Shcherbata, Michael Meinecke, Dietmar Riedel, Sven Dennerlein, Peter Rehling, Stefan Jakobs","doi":"10.26508/lsa.202302177","DOIUrl":"10.26508/lsa.202302177","url":null,"abstract":"Cristae are invaginations of the mitochondrial inner membrane that are crucial for cellular energy metabolism. The formation of cristae requires the presence of a protein complex known as MICOS, which is conserved across eukaryotic species. One of the subunits of this complex, MIC10, is a transmembrane protein that supports cristae formation by oligomerization. In Drosophila melanogaster, three MIC10-like proteins with different tissue-specific expression patterns exist. We demonstrate that CG41128/MINOS1b/DmMIC10b is the major MIC10 orthologue in flies. Its loss destabilizes MICOS, disturbs cristae architecture, and reduces the life span and fertility of flies. We show that DmMIC10b has a unique ability to polymerize into bundles of filaments, which can remodel mitochondrial crista membranes. The formation of these filaments relies on conserved glycine and cysteine residues, and can be suppressed by the co-expression of other Drosophila MICOS proteins. These findings provide new insights into the regulation of MICOS in flies, and suggest potential mechanisms for the maintenance of mitochondrial ultrastructure.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10803214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Single variant, yet "double trouble": TSC and KBG syndrome because of a large de novo inversion. 单一变异，却有 "双重麻烦"：TSC和KBG综合征，因为一个巨大的新倒位。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-22 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302115

Victoria Rodrigues Alves Barbosa, Tatiana Maroilley, Catherine Diao, Leslie Colvin-James, Renee Perrier, Maja Tarailo-Graovac

{"title":"Single variant, yet \"double trouble\": TSC and KBG syndrome because of a large de novo inversion.","authors":"Victoria Rodrigues Alves Barbosa, Tatiana Maroilley, Catherine Diao, Leslie Colvin-James, Renee Perrier, Maja Tarailo-Graovac","doi":"10.26508/lsa.202302115","DOIUrl":"10.26508/lsa.202302115","url":null,"abstract":"Despite the advances in high-throughput sequencing, many rare disease patients remain undiagnosed. In particular, the patients with well-defined clinical phenotypes and established clinical diagnosis, yet missing or partial genetic diagnosis, may hold a clue to more complex genetic mechanisms of a disease that could be missed by available clinical tests. Here, we report a patient with a clinical diagnosis of Tuberous sclerosis, combined with unusual secondary features, but negative clinical tests including TSC1 and TSC2 Short-read whole-genome sequencing combined with advanced bioinformatics analyses were successful in uncovering a de novo pericentric 87-Mb inversion with breakpoints in TSC2 and ANKRD11, which explains the TSC clinical diagnosis, and confirms a second underlying monogenic disorder, KBG syndrome. Our findings illustrate how complex variants, such as large inversions, may be missed by clinical tests and further highlight the importance of well-defined clinical diagnoses in uncovering complex molecular mechanisms of a disease, such as complex variants and \"double trouble\" effects.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10803213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Absence of the RING domain in MID1 results in patterning defects in the developing human brain. MID1 的 RING 结构域缺失会导致发育中的人类大脑出现模式化缺陷。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-18 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302288

Sarah Frank, Elisa Gabassi, Stephan Käseberg, Marco Bertin, Lea Zografidou, Daniela Pfeiffer, Heiko Brennenstuhl, Sven Falk, Marisa Karow, Susann Schweiger

{"title":"Absence of the RING domain in MID1 results in patterning defects in the developing human brain.","authors":"Sarah Frank, Elisa Gabassi, Stephan Käseberg, Marco Bertin, Lea Zografidou, Daniela Pfeiffer, Heiko Brennenstuhl, Sven Falk, Marisa Karow, Susann Schweiger","doi":"10.26508/lsa.202302288","DOIUrl":"10.26508/lsa.202302288","url":null,"abstract":"The X-linked form of Opitz BBB/G syndrome (OS) is a monogenic disorder in which symptoms are established early during embryonic development. OS is caused by pathogenic variants in the X-linked gene MID1 Disease-associated variants are distributed across the entire gene locus, except for the N-terminal really interesting new gene (RING) domain that encompasses the E3 ubiquitin ligase activity. By using genome-edited human induced pluripotent stem cell lines, we here show that absence of isoforms containing the RING domain of MID1 causes severe patterning defects in human brain organoids. We observed a prominent neurogenic deficit with a reduction in neural tissue and a concomitant increase in choroid plexus-like structures. Transcriptome analyses revealed a deregulation of patterning pathways very early on, even preceding neural induction. Notably, the observed phenotypes starkly contrast with those observed in MID1 full-knockout organoids, indicating the presence of a distinct mechanism that underlies the patterning defects. The severity and early onset of these phenotypes could potentially account for the absence of patients carrying pathogenic variants in exon 1 of the MID1 gene coding for the N-terminal RING domain.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Reduced myeloid commitment and increased uptake by macrophages of stem cell-derived HPS2 neutrophils. 干细胞衍生的 HPS2 中性粒细胞减少了髓细胞的承诺，增加了巨噬细胞的吸收。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-18 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302263

Steven Ds Webbers, Cathelijn Em Aarts, Bart Klein, Dané Koops, Judy Geissler, Anton Tj Tool, Robin van Bruggen, Emile van den Akker, Taco W Kuijpers

{"title":"Reduced myeloid commitment and increased uptake by macrophages of stem cell-derived HPS2 neutrophils.","authors":"Steven Ds Webbers, Cathelijn Em Aarts, Bart Klein, Dané Koops, Judy Geissler, Anton Tj Tool, Robin van Bruggen, Emile van den Akker, Taco W Kuijpers","doi":"10.26508/lsa.202302263","DOIUrl":"10.26508/lsa.202302263","url":null,"abstract":"Hermansky-Pudlak syndrome type 2 (HPS2) is a rare autosomal recessive disorder, caused by mutations in the AP3B1 gene, encoding the β3A subunit of the adapter protein complex 3. This results in mis-sorting of proteins within the cell. A clinical feature of HPS2 is severe neutropenia. Current HPS2 animal models do not recapitulate the human disease. Hence, we used induced pluripotent stem cells (iPSCs) of an HPS2 patient to study granulopoiesis. Development into CD15POS cells was reduced, but HPS2-derived CD15POS cells differentiated into segmented CD11b+CD16hi neutrophils. These HPS2 neutrophils phenocopied their circulating counterparts showing increased CD63 expression, impaired degranulation capacity, and intact NADPH oxidase activity. Most noticeable was the decrease in neutrophil yield during the final days of HPS2 iPSC cultures. Although neutrophil viability was normal, CD15NEG macrophages were readily phagocytosing neutrophils, contributing to the limited neutrophil output in HPS2. In this iPSC model, HPS2 neutrophil development is affected by a slower rate of development and by macrophage-mediated clearance during neutrophil maturation.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Synaptobrevin2 monomers and dimers differentially engage to regulate the functional trans-SNARE assembly. Synaptobrevin2单体和二聚体以不同方式参与调节功能性跨SNARE组装。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-18 Print Date: 2024-04-01 DOI: 10.26508/lsa.202402568

Swapnali S Patil, Kinjal Sanghrajka, Malavika Sriram, Aritra Chakraborty, Sougata Majumdar, Bhavya R Bhaskar, Debasis Das

引用次数: 0

Spatiotemporal DNA methylation dynamics shape megabase-scale methylome landscapes. 时空 DNA 甲基化动力学塑造了巨碱基尺度的甲基组景观。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-17 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302403

Hidehiro Toh, Hiroyuki Sasaki

{"title":"Spatiotemporal DNA methylation dynamics shape megabase-scale methylome landscapes.","authors":"Hidehiro Toh, Hiroyuki Sasaki","doi":"10.26508/lsa.202302403","DOIUrl":"10.26508/lsa.202302403","url":null,"abstract":"DNA methylation is an essential epigenetic mechanism that regulates cellular reprogramming and development. Studies using whole-genome bisulfite sequencing have revealed distinct DNA methylome landscapes in human and mouse cells and tissues. However, the factors responsible for the differences in megabase-scale methylome patterns between cell types remain poorly understood. By analyzing publicly available 258 human and 301 mouse whole-genome bisulfite sequencing datasets, we reveal that genomic regions rich in guanine and cytosine, when located near the nuclear center, are highly susceptible to both global DNA demethylation and methylation events during embryonic and germline reprogramming. Furthermore, we found that regions that generate partially methylated domains during global DNA methylation are more likely to resist global DNA demethylation, contain high levels of adenine and thymine, and are adjacent to the nuclear lamina. The spatial properties of genomic regions, influenced by their guanine-cytosine content, are likely to affect the accessibility of molecules involved in DNA (de)methylation. These properties shape megabase-scale DNA methylation patterns and change as cells differentiate, leading to the emergence of different megabase-scale methylome patterns across cell types.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10794778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139486013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Enhancer mutations modulate the severity of chemotherapy-induced myelosuppression. 增强子突变可调节化疗引起的骨髓抑制的严重程度。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-01-16 Print Date: 2024-03-01 DOI: 10.26508/lsa.202302244

Artemy Zhigulev, Zandra Norberg, Julie Cordier, Rapolas Spalinskas, Hassan Bassereh, Niclas Björn, Sailendra Pradhananga, Henrik Gréen, Pelin Sahlén

{"title":"Enhancer mutations modulate the severity of chemotherapy-induced myelosuppression.","authors":"Artemy Zhigulev, Zandra Norberg, Julie Cordier, Rapolas Spalinskas, Hassan Bassereh, Niclas Björn, Sailendra Pradhananga, Henrik Gréen, Pelin Sahlén","doi":"10.26508/lsa.202302244","DOIUrl":"10.26508/lsa.202302244","url":null,"abstract":"Non-small cell lung cancer is often diagnosed at advanced stages, and many patients are still treated with classical chemotherapy. The unselective nature of chemotherapy often results in severe myelosuppression. Previous studies showed that protein-coding mutations could not fully explain the predisposition to myelosuppression. Here, we investigate the possible role of enhancer mutations in myelosuppression susceptibility. We produced transcriptome and promoter-interaction maps (using HiCap) of three blood stem-like cell lines treated with carboplatin or gemcitabine. Taking advantage of publicly available enhancer datasets, we validated HiCap results in silico and in living cells using epigenetic CRISPR technology. We also developed a network approach for interactome analysis and detection of differentially interacting genes. Differential interaction analysis provided additional information on relevant genes and pathways for myelosuppression compared with differential gene expression analysis at the bulk level. Moreover, we showed that enhancers of differentially interacting genes are highly enriched for variants associated with differing levels of myelosuppression. Altogether, our work represents a prominent example of integrative transcriptome and gene regulatory datasets analysis for the functional annotation of noncoding mutations.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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