Life Science Alliance最新文献_第8页

Identification of single-cell blasts in pediatric acute myeloid leukemia using an autoencoder. 利用自动编码器识别小儿急性髓性白血病中的单细胞突变。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-27 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402674

Alice Driessen, Susanne Unger, An-Phi Nguyen, Rhonda E Ries, Soheil Meshinchi, Stefanie Kreutmair, Chiara Alberti, Pavel Sumazin, Richard Aplenc, Michele S Redell, Burkhard Becher, María Rodríguez Martínez

{"title":"Identification of single-cell blasts in pediatric acute myeloid leukemia using an autoencoder.","authors":"Alice Driessen, Susanne Unger, An-Phi Nguyen, Rhonda E Ries, Soheil Meshinchi, Stefanie Kreutmair, Chiara Alberti, Pavel Sumazin, Richard Aplenc, Michele S Redell, Burkhard Becher, María Rodríguez Martínez","doi":"10.26508/lsa.202402674","DOIUrl":"10.26508/lsa.202402674","url":null,"abstract":"Pediatric acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis and high relapse rate. Current challenges in the identification of immunotherapy targets arise from patient-specific blast immunophenotypes and their change during disease progression. To overcome this, we present a new computational research tool to rapidly identify malignant cells. We generated single-cell flow cytometry profiles of 21 pediatric AML patients with matched samples at diagnosis, remission, and relapse. We coupled a classifier to an autoencoder for anomaly detection and classified malignant blasts with 90% accuracy. Moreover, our method assigns a developmental stage to blasts at the single-cell level, improving current classification approaches based on differentiation of the dominant phenotype. We observed major immunophenotype and developmental stage alterations between diagnosis and relapse. Patients with KMT2A rearrangement had more profound changes in their blast immunophenotypes at relapse compared to patients with other molecular features. Our method provides new insights into the immunophenotypic composition of AML blasts in an unbiased fashion and can help to define immunotherapy targets that might improve personalized AML treatment.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080793","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

mTORC1 hampers Hedgehog signaling in Tsc2 deficient cells. 在缺乏 Tsc2 的细胞中，mTORC1 阻碍了刺猬信号的传递。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-26 Print Date: 2024-11-01 DOI: 10.26508/lsa.202302419

Lasse Jonsgaard Larsen, Elsebet Østergaard, Lisbeth Birk Møller

{"title":"mTORC1 hampers Hedgehog signaling in Tsc2 deficient cells.","authors":"Lasse Jonsgaard Larsen, Elsebet Østergaard, Lisbeth Birk Møller","doi":"10.26508/lsa.202302419","DOIUrl":"10.26508/lsa.202302419","url":null,"abstract":"The mTORC1-complex is negatively regulated by TSC1 and TSC2. Activation of Hedgehog signaling is strictly dependent on communication between Smoothened and the Hedgehog-signaling effector and transcription factor, GLI2, in the primary cilium. Details about this communication are not known, and we wanted to explore this further. Here we report that in Tsc2 -/- MEFs constitutively activated mTORC1 led to mis-localization of Smoothened to the plasma membrane, combined with increased concentration of GLI2 in the cilia and reduced Hedgehog signaling, measured by reduced expression of the Hedgehog target gene, Gli1 Inhibition of mTORC1 rescued the cellular localization of Smoothened to the cilia, reduced the cilia concentration of GLI2, and restored Hedgehog signaling. Our results reveal evidence for a two-step activation process of GLI2. The first step includes GLI2 stabilization and cilium localization, whereas the second step includes communication with cilia-localized Smoothened. We found that mTORC1 inhibits the second step. This is the first demonstration that mTORC1 is involved in the regulation of Hedgehog signaling.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073215","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

CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow. CC2D1A会导致纤毛症、智力障碍、异位发育、肾发育不良和脑脊液流动异常。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-21 Print Date: 2024-10-01 DOI: 10.26508/lsa.202402708

Angelina Haesoo Kim, Irmak Sakin, Stephen Viviano, Gulten Tuncel, Stephanie Marie Aguilera, Gizem Goles, Lauren Jeffries, Weizhen Ji, Saquib A Lakhani, Canan Ceylan Kose, Fatma Silan, Sukru Sadik Oner, Oktay I Kaplan, Mahmut Cerkez Ergoren, Ketu Mishra-Gorur, Murat Gunel, Sebnem Ozemri Sag, Sehime G Temel, Engin Deniz

{"title":"CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow.","authors":"Angelina Haesoo Kim, Irmak Sakin, Stephen Viviano, Gulten Tuncel, Stephanie Marie Aguilera, Gizem Goles, Lauren Jeffries, Weizhen Ji, Saquib A Lakhani, Canan Ceylan Kose, Fatma Silan, Sukru Sadik Oner, Oktay I Kaplan, Mahmut Cerkez Ergoren, Ketu Mishra-Gorur, Murat Gunel, Sebnem Ozemri Sag, Sehime G Temel, Engin Deniz","doi":"10.26508/lsa.202402708","DOIUrl":"10.26508/lsa.202402708","url":null,"abstract":"Intellectual and developmental disabilities result from abnormal nervous system development. Over a 1,000 genes have been associated with intellectual and developmental disabilities, driving continued efforts toward dissecting variant functionality to enhance our understanding of the disease mechanism. This report identified two novel variants in CC2D1A in a cohort of four patients from two unrelated families. We used multiple model systems for functional analysis, including Xenopus, Drosophila, and patient-derived fibroblasts. Our experiments revealed that cc2d1a is expressed explicitly in a spectrum of ciliated tissues, including the left-right organizer, epidermis, pronephric duct, nephrostomes, and ventricular zone of the brain. In line with this expression pattern, loss of cc2d1a led to cardiac heterotaxy, cystic kidneys, and abnormal CSF circulation via defective ciliogenesis. Interestingly, when we analyzed brain development, mutant tadpoles showed abnormal CSF circulation only in the midbrain region, suggesting abnormal local CSF flow. Furthermore, our analysis of the patient-derived fibroblasts confirmed defective ciliogenesis, further supporting our observations. In summary, we revealed novel insight into the role of CC2D1A by establishing its new critical role in ciliogenesis and CSF circulation.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017958","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

Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration. 通过研究肝脏与胰腺之间的相互关系，可以发现钼辅助因子在β细胞再生中的作用。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-19 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402771

Christos Karampelias, Bianca Băloiu, Birgit Rathkolb, Patricia da Silva-Buttkus, Etty Bachar-Wikström, Susan Marschall, Helmut Fuchs, Valerie Gailus-Durner, Lianhe Chu, Martin Hrabě de Angelis, Olov Andersson

{"title":"Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration.","authors":"Christos Karampelias, Bianca Băloiu, Birgit Rathkolb, Patricia da Silva-Buttkus, Etty Bachar-Wikström, Susan Marschall, Helmut Fuchs, Valerie Gailus-Durner, Lianhe Chu, Martin Hrabě de Angelis, Olov Andersson","doi":"10.26508/lsa.202402771","DOIUrl":"10.26508/lsa.202402771","url":null,"abstract":"Regeneration of insulin-producing β-cells is an alternative avenue to manage diabetes, and it is crucial to unravel this process in vivo during physiological responses to the lack of β-cells. Here, we aimed to characterize how hepatocytes can contribute to β-cell regeneration, either directly or indirectly via secreted proteins or metabolites, in a zebrafish model of β-cell loss. Using lineage tracing, we show that hepatocytes do not directly convert into β-cells even under extreme β-cell ablation conditions. A transcriptomic analysis of isolated hepatocytes after β-cell ablation displayed altered lipid- and glucose-related processes. Based on the transcriptomics, we performed a genetic screen that uncovers a potential role of the molybdenum cofactor (Moco) biosynthetic pathway in β-cell regeneration and glucose metabolism in zebrafish. Consistently, molybdenum cofactor synthesis 2 (Mocs2) haploinsufficiency in mice indicated dysregulated glucose metabolism and liver function. Together, our study sheds light on the liver-pancreas crosstalk and suggests that the molybdenum cofactor biosynthesis pathway should be further studied in relation to glucose metabolism and diabetes.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004575","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

Enhancing uterine receptivity for embryo implantation through controlled collagenase intervention. 通过受控胶原酶干预提高子宫对胚胎植入的接受能力。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-16 Print Date: 2024-10-01 DOI: 10.26508/lsa.202402656

Eldar Zehorai, Tamar Gross Lev, Elee Shimshoni, Ron Hadas, Idan Adir, Ofra Golani, Guillaume Molodij, Ram Eitan, Karl E Kadler, Orit Kollet, Michal Neeman, Nava Dekel, Inna Solomonov, Irit Sagi

{"title":"Enhancing uterine receptivity for embryo implantation through controlled collagenase intervention.","authors":"Eldar Zehorai, Tamar Gross Lev, Elee Shimshoni, Ron Hadas, Idan Adir, Ofra Golani, Guillaume Molodij, Ram Eitan, Karl E Kadler, Orit Kollet, Michal Neeman, Nava Dekel, Inna Solomonov, Irit Sagi","doi":"10.26508/lsa.202402656","DOIUrl":"10.26508/lsa.202402656","url":null,"abstract":"Ineffective endometrial matrix remodeling, a key factor in infertility, impedes embryo implantation in the uterine wall. Our study reveals the cellular and molecular impact of human collagenase-1 administration in mouse uteri, demonstrating enhanced embryo implantation rates. Collagenase-1 promotes remodeling of the endometrial ECM, degrading collagen fibers and proteoglycans. This process releases matrix-bound bioactive factors (e.g., VEGF, decorin), facilitating vascular permeability and angiogenesis. Collagenase-1 elevates embryo implantation regulators, including NK cell infiltration and the key cytokine LIF. Remarkably, uterine tissue maintains structural integrity despite reduced endometrial collagen fiber tension. In-utero collagenase-1 application rescues implantation in heat stress and embryo transfer models, known for low implantation rates. Importantly, ex vivo exposure of human uterine tissue to collagenase-1 induces collagen de-tensioning and VEGF release, mirroring remodeling observed in mice. Our research highlights the potential of collagenases to induce and orchestrate cellular and molecular processes enhancing uterine receptivity for effective embryo implantation. This innovative approach underscores ECM remodeling mechanisms critical for embryo implantation.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996097","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

Neutrophil-avid nanocarrier uptake by STAT3 dominant-negative hyper-IgE syndrome patient neutrophils. STAT3显性阴性高IgE综合征患者中性粒细胞对纳米载体的吸收。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-12 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402618

Kathryn M Rubey, Alexandra Freeman, Alexander R Mukhitov, Andrew J Paris, Susan M Lin, Ryan Rue, Hossein Fazelinia, Lynn A Spruce, Jennifer Roof, Jacob S Brenner, Jennifer Heimall, Vera P Krymskaya

{"title":"Neutrophil-avid nanocarrier uptake by STAT3 dominant-negative hyper-IgE syndrome patient neutrophils.","authors":"Kathryn M Rubey, Alexandra Freeman, Alexander R Mukhitov, Andrew J Paris, Susan M Lin, Ryan Rue, Hossein Fazelinia, Lynn A Spruce, Jennifer Roof, Jacob S Brenner, Jennifer Heimall, Vera P Krymskaya","doi":"10.26508/lsa.202402618","DOIUrl":"10.26508/lsa.202402618","url":null,"abstract":"Recurrent infections are a hallmark of STAT3 dominant-negative hyper-IgE syndrome (STAT3 HIES), a rare immunodeficiency syndrome previously known as Jobs syndrome, along with elevated IgE levels and impaired neutrophil function. We have been developing nanoparticles with neutrophil trophism that home to the sites of infection via these first-responder leukocytes, named neutrophil-avid nanocarriers (NANs). Here, we demonstrate that human neutrophils can phagocytose nanogels (NGs), a type of NAN, with enhanced uptake after particle serum opsonization, comparing neutrophils from healthy individuals to those with STAT3 HIES, where both groups exhibit NG uptake; however, the patient group showed reduced phagocytosis efficiency with serum-opsonized NANs. Proteomic analysis of NG protein corona revealed complement components, particularly C3, as predominant in both groups. Difference between groups includes STAT3 HIES samples with higher neutrophil protein and lower acute-phase protein expression. The study suggests that despite neutrophil dysfunction in STAT3 HIES, NANs have potential for directed delivery of cargo therapeutics to improve neutrophil infection clearance.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971414","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

JAK inhibition with tofacitinib rapidly increases contractile force in human skeletal muscle. 用托法替尼抑制 JAK 可迅速增加人体骨骼肌的收缩力。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-09 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402885

Joseph B Shrager, Ryan Randle, Myung Lee, Syed Saadan Ahmed, Winston Trope, Natalie Lui, George Poultsides, Doug Liou, Brendan Visser, Jeffrey A Norton, Shannon M Nesbit, Hao He, Ntemena Kapula, Bailey Wallen, Emmanuel Fatodu, Cheyenne A Sadeghi, Harrison B Konsker, Irmina Elliott, Brandon Guenthart, Leah Backhus, Roger Cooke, Mark Berry, Huibin Tang

{"title":"JAK inhibition with tofacitinib rapidly increases contractile force in human skeletal muscle.","authors":"Joseph B Shrager, Ryan Randle, Myung Lee, Syed Saadan Ahmed, Winston Trope, Natalie Lui, George Poultsides, Doug Liou, Brendan Visser, Jeffrey A Norton, Shannon M Nesbit, Hao He, Ntemena Kapula, Bailey Wallen, Emmanuel Fatodu, Cheyenne A Sadeghi, Harrison B Konsker, Irmina Elliott, Brandon Guenthart, Leah Backhus, Roger Cooke, Mark Berry, Huibin Tang","doi":"10.26508/lsa.202402885","DOIUrl":"10.26508/lsa.202402885","url":null,"abstract":"Reduction in muscle contractile force associated with many clinical conditions incurs serious morbidity and increased mortality. Here, we report the first evidence that JAK inhibition impacts contractile force in normal human muscle. Muscle biopsies were taken from patients who were randomized to receive tofacitinib (n = 16) or placebo (n = 17) for 48 h. Single-fiber contractile force and molecular studies were carried out. The contractile force of individual diaphragm myofibers pooled from the tofacitinib group (n = 248 fibers) was significantly higher than those from the placebo group (n = 238 fibers), with a 15.7% greater mean maximum specific force (P = 0.0016). Tofacitinib treatment similarly increased fiber force in the serratus anterior muscle. The increased force was associated with reduced muscle protein oxidation and FoxO-ubiquitination-proteasome signaling, and increased levels of smooth muscle MYLK. Inhibition of MYLK attenuated the tofacitinib-dependent increase in fiber force. These data demonstrate that tofacitinib increases the contractile force of skeletal muscle and offers several underlying mechanisms. Inhibition of the JAK-STAT pathway is thus a potential new therapy for the muscle dysfunction that occurs in many clinical conditions.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913164","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

Distribution of lipid droplets in hippocampal neurons and microglia: impact of diabetes and exercise. 海马神经元和小胶质细胞中脂滴的分布：糖尿病和运动的影响。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-08 Print Date: 2024-10-01 DOI: 10.26508/lsa.202302239

Gezime Seferi, Harald S Mjønes, Mona Havik, Herman Reiersen, Knut Tomas Dalen, Kaja Nordengen, Cecilie Morland

{"title":"Distribution of lipid droplets in hippocampal neurons and microglia: impact of diabetes and exercise.","authors":"Gezime Seferi, Harald S Mjønes, Mona Havik, Herman Reiersen, Knut Tomas Dalen, Kaja Nordengen, Cecilie Morland","doi":"10.26508/lsa.202302239","DOIUrl":"10.26508/lsa.202302239","url":null,"abstract":"Neuroinflammation, aging, and neurodegenerative disorders are associated with excessive accumulation of neutral lipids in lipid droplets (LDs) in microglia. Type 2 diabetes mellitus (T2DM) may cause neuroinflammation and is a risk factor for neurodegenerative disorders. Here, we show that hippocampal pyramidal neurons contain smaller, more abundant LDs than their neighboring microglia. The density of LDs varied between pyramidal cells in adjacent subregions, with CA3 neurons containing more LDs than CA1 neurons. Within the CA3 region, a gradual increase in the LD content along the pyramidal layer from the hilus toward CA2 was observed. Interestingly, the high neuronal LD content correlated with less ramified microglial morphotypes. Using the db/db model of T2DM, we demonstrated that diabetes increased the number of LDs per microglial cell without affecting the neuronal LD density. High-intensity interval exercise induced smaller changes in the number of LDs in microglia but was not sufficient to counteract the diabetes-induced changes in LD accumulation. The changes observed in response to T2DM may contribute to the cerebral effects of T2DM and provide a mechanistic link between T2DM and neurodegenerative disorders.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907010","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

PPM1G dephosphorylates eIF4E in control of mRNA translation and cell proliferation. PPM1G 可使 eIF4E 去磷酸化，从而控制 mRNA 翻译和细胞增殖。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-07 Print Date: 2024-10-01 DOI: 10.26508/lsa.202402755

Peng Wang, Zixian Li, Sung-Hoon Kim, Haijin Xu, Hao Huang, Chutong Yang, Abby Snape, Jung-Hyun Choi, Sara Bermudez, Marie-Noelle Boivin, Nicolas Ferry, Jason Karamchandani, Bhushan Nagar, Nahum Sonenberg

引用次数: 0

A scalable approach to topic modelling in single-cell data by approximate pseudobulk projection. 通过近似伪块投影对单细胞数据进行主题建模的可扩展方法。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-06 Print Date: 2024-10-01 DOI: 10.26508/lsa.202402713

Sishir Subedi, Tomokazu S Sumida, Yongjin P Park

{"title":"A scalable approach to topic modelling in single-cell data by approximate pseudobulk projection.","authors":"Sishir Subedi, Tomokazu S Sumida, Yongjin P Park","doi":"10.26508/lsa.202402713","DOIUrl":"10.26508/lsa.202402713","url":null,"abstract":"Probabilistic topic modelling has become essential in many types of single-cell data analysis. Based on probabilistic topic assignments in each cell, we identify the latent representation of cellular states. A dictionary matrix, consisting of topic-specific gene frequency vectors, provides interpretable bases to be compared with known cell type-specific marker genes and other pathway annotations. However, fitting a topic model on a large number of cells would require heavy computational resources-specialized computing units, computing time and memory. Here, we present a scalable approximation method customized for single-cell RNA-seq data analysis, termed ASAP, short for Annotating a Single-cell data matrix by Approximate Pseudobulk estimation. Our approach is more accurate than existing methods but requires orders of magnitude less computing time, leaving much lower memory consumption. We also show that our approach is widely applicable for atlas-scale data analysis; our method seamlessly integrates single-cell and bulk data in joint analysis, not requiring additional preprocessing or feature selection steps.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897728","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