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JOURNAL ARTICLE
Sherry Dong, Kaiwen Deng, Xiuzhen Huang
MOTIVATION: Annotating cell types is a challenging yet essential task in analyzing single-cell RNA sequencing data. However, due to the lack of a gold standard, it is difficult to evaluate the algorithms fairly and an overfitting algorithm may be favored in benchmarks. To address this challenge, we developed a deep learning-based single-cell type prediction tool that assigns the cell type to 265 different cell types for humans, based on data from approximately five million cells. RESULTS: We achieved a median area under the ROC curve (AUC) of 0...
2024: Bioinform Adv
#22
JOURNAL ARTICLE
Zijing Gao, Rui Jiang, Shengquan Chen
SUMMARY: Chromatin accessibility serves as a critical measurement of physical contact between nuclear macromolecules and DNA sequence, providing valuable insights into the comprehensive landscape of regulatory mechanisms, thus we previously developed the OpenAnnotate web server. However, as an increasing number of epigenomic analysis software tools emerged, web-based annotation often faced limitations and inconveniences when integrated into these software pipelines. To address these issues, we here develop two software packages named OpenAnnotatePy and OpenAnnotateR...
2024: Bioinform Adv
#23
JOURNAL ARTICLE
Evan Lammertse, Siran Li, Jude Kendall, Catherine Kim, Patrick Morris, Nissim Ranade, Dan Levy, Michael Wigler, Eric Brouzes
Single-cell genomics has revolutionized tissue analysis by revealing the genetic program of individual cells. The key aspect of the technology is the use of barcoded beads to unambiguously tag sequences originating from a single cell. The generation of unique barcodes on beads is mainly achieved by split-pooling methods, which are labor-intensive due to repeated washing steps. Towards the automation of the split-pooling method, we developed a simple method to magnetize hydrogel beads. We show that these hydrogel beads provide increased yields and washing efficiencies for purification procedures...
January 22, 2024: Advanced Materials Technologies
#24
Hope M Healey, Hayden B Penn, Clayton M Small, Susan Bassham, Vithika Goyal, Micah A Woods, William A Cresko
UNLABELLED: Seahorses, pipefishes, and seadragons are fishes from the family Syngnathidae that have evolved extraordinary traits including male pregnancy, elongated snouts, loss of teeth, and dermal bony armor. The developmental genetic and cellular changes that led to the evolution of these traits are largely unknown. Recent syngnathid genomes revealed suggestive gene content differences and provide the opportunity for detailed genetic analyses. We created a single cell RNA sequencing atlas of Gulf pipefish embryos to understand the developmental basis of four traits: derived head shape, toothlessness, dermal armor, and male pregnancy...
April 9, 2024: bioRxiv
#25
Jisun So, Olivia Strobel, Jamie Wann, Kyungchan Kim, Avishek Paul, Dominic J Acri, Luke C Dabin, Jungsu Kim, Hyun Cheol Roh
Single nucleus RNA sequencing (snRNA-seq), an alternative to single cell RNA sequencing (scRNA-seq), encounters technical challenges in obtaining high-quality nuclei and RNA, persistently hindering its applications. Here, we present a robust technique for isolating nuclei across various tissue types, remarkably enhancing snRNA-seq data quality. Employing this approach, we comprehensively characterize the depot-dependent cellular dynamics of various cell types underlying adipose tissue remodeling during obesity...
April 8, 2024: bioRxiv
#26
Ayse Maraslioglu-Sperber, Fabian Blanc, Stefan Heller, Nesrine Benkafadar
Hearing impairment arises from the loss of either type of cochlear sensory hair cells. Inner hair cells act as primary sound transducers, while outer hair cells enhance sound-induced vibrations within the organ of Corti. Established models, such as systemic administration of ototoxic aminoglycosides, yield inconsistent and variable hair cell death in mice. Overcoming this limitation, we developed a method involving surgical delivery of a hyperosmotic sisomicin solution into the posterior semicircular canal of adult mice...
April 1, 2024: Research Square
#27
Ruihan Luo, Jiajia Liu, Jianguo Wen, Xiaobo Zhou
Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells...
April 5, 2024: Research Square
#28
Shadi Zahedi, Kent Riemondy, Andrea M Griesinger, Andrew M Donson, Rui Fu, Michele Crespo, John DeSisto, Madeline M Groat, Emil Bratbak, Adam Green, Todd C Hankinson, Michael Handler, Rajeev Vibhakar, Nicholas Willard, Nicholas K Foreman, Jean Mulcahy Levy
UNLABELLED: Pediatric low-grade gliomas (pLGG) comprise 35% of all brain tumors. Despite favorable survival, patients experience significant morbidity from disease and treatments. A deeper understanding of pLGG biology is essential to identify novel, more effective, and less toxic therapies. We utilized single cell RNA sequencing (scRNA-seq), spatial transcriptomics, and cytokine analyses to characterize and understand tumor and immune cell heterogeneity across pLGG. scRNA-seq revealed tumor and immune cells within the tumor microenvironment (TME)...
April 10, 2024: bioRxiv
#29
Jeremy M Shea, Saul A Villeda
During aging, microglia - the resident macrophages of the brain - exhibit dystrophic phenotypes and contribute to age-related neuroinflammation. While numerous hallmarks of age-related microglia dystrophy have been elucidated, the progression from homeostasis to dysfunction during the aging process remains unresolved. To bridge this gap in knowledge, we undertook complementary cellular and molecular analyses of microglia in the mouse hippocampus across the adult lifespan and in the experimental aging model of heterochronic parabiosis...
April 9, 2024: bioRxiv
#30
Shi B Chia, Bryan J Johnson, Junxiao Hu, Roel Vermeulen, Marc Chadeau-Hyam, Fernando Guntoro, Hugh Montgomery, Meher Preethi Boorgula, Varsha Sreeka, Andrew Goodspeed, Bennett Davenport, Felipe V Pereira, Vadym Zaberezhnyy, Wolfgang E Schleicher, Dexiang Gao, Andreia N Cadar, Michael Papanicolaou, Afshin Beheshti, Stephen B Baylin, James Costello, Jenna M Bartley, Thomas E Morrison, Julio A Aguirre-Ghiso, Mercedes Rincon, James DeGregori
Breast cancer is the second most common cancer globally. Most deaths from breast cancer are due to metastatic disease which often follows long periods of clinical dormancy 1 . Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCC) is crucial for addressing metastatic progression. Infection with respiratory viruses (e.g. influenza or SARS-CoV-2) is common and triggers an inflammatory response locally and systemically 2,3 . Here we show that influenza virus infection leads to loss of the pro-dormancy mesenchymal phenotype in breast DCC in the lung, causing DCC proliferation within days of infection, and a greater than 100-fold expansion of carcinoma cells into metastatic lesions within two weeks...
April 5, 2024: Research Square
#31
Gabriella Rice, Olivia Farrelly, Sixia Huang, Paola Kuri, Ezra Curtis, Lisa Ohman, Ning Li, Christopher Lengner, Vivian Lee, Panteleimon Rompolas
Adult tissues with high cellular turnover require a balance between stem cell renewal and differentiation, yet the mechanisms underlying this equilibrium are unclear. The cornea exhibits a polarized lateral flow of progenitors from the peripheral stem cell niche to the center; attributed to differences in cellular fate. To identify genes that are critical for regulating the asymmetric fates of limbal stem cells and their transient amplified progeny in the central cornea, we utilized an in vivo cell cycle reporter to isolate proliferating basal cells across the anterior ocular surface epithelium and perform single-cell transcriptional analysis...
April 11, 2024: bioRxiv
#32
Malte Luecken, Scott Gigante, Daniel Burkhardt, Robrecht Cannoodt, Daniel Strobl, Nikolay Markov, Luke Zappia, Giovanni Palla, Wesley Lewis, Daniel Dimitrov, Michael Vinyard, Daniel Magruder, Alma Andersson, Emma Dann, Qian Qin, Dominik Otto, Michal Klein, Olga Botvinnik, Louise Deconinck, Kai Waldrant, Bastian Rieck, Constantin Ahlmann-Eltze, Eduardo da Veiga Beltrame, Andrew Benz, Carmen Bravo González-Blas, Ann Chen, Benjamin DeMeo, Can Ergen, Swann Floc'hlay, Adam Gayoso, Stephanie Hicks, Yuge Ji, Vitalii Kleshchevnikov, Gioele La Manno, Maximilian Lombardo, Romain Lopez, Dario Righelli, Hirak Sarkar, Valentine Svensson, Alexander Tong, Galen Xing, Chenling Xu, Jonathan Bloom, Angela Pisco, Julio Saez-Rodriguez, Drausin Wulsin, Luca Pinello, Yvan Saeys, Fabian Theis, Smita Krishnaswamy
With the growing number of single-cell analysis tools, benchmarks are increasingly important to guide analysis and method development. However, a lack of standardisation and extensibility in current benchmarks limits their usability, longevity, and relevance to the community. We present Open Problems, a living, extensible, community-guided benchmarking platform including 10 current single-cell tasks that we envision will raise standards for the selection, evaluation, and development of methods in single-cell analysis...
April 4, 2024: Research Square
#33
Malika Hale, Kennidy K Takehara, Christopher D Thouvenel, Dina A Moustafa, Andrea Repele, Mary F Fontana, Jason Netland, Sharon McNamara, Ronald L Gibson, Joanna B Goldberg, David J Rawlings, Marion Pepper
Pseudomonas aeruginosa (PA) is an opportunistic, frequently multidrug-resistant pathogen that can cause severe infections in hospitalized patients. Antibodies against the PA virulence factor, PcrV, protect from death and disease in a variety of animal models. However, clinical trials of PcrV-binding antibody-based products have thus far failed to demonstrate benefit. Prior candidates were derivations of antibodies identified using protein-immunized animal systems and required extensive engineering to optimize binding and/or reduce immunogenicity...
April 12, 2024: bioRxiv
#34
Wenjun Shen, Cheng Liu, Yunfei Hu, Yuanfang Lei, Hau-San Wong, Si Wu, Xin Maizie Zhou
A main limitation of bulk transcriptomic technologies is that individual measurements normally contain contributions from multiple cell populations, impeding the identification of cellular heterogeneity within diseased tissues. To extract cellular insights from existing large cohorts of bulk transcriptomic data, we present CSsingle, a novel method designed to accurately deconvolve bulk data into a predefined set of cell types using a scRNA-seq reference. Through comprehensive benchmark evaluations and analyses using diverse real data sets, we reveal the systematic bias inherent in existing methods, stemming from differences in cell size or library size...
April 9, 2024: bioRxiv
#35
Jing Liu, Federica Mosti, Hanzhi T Zhao, Jesus E Sotelo-Fonseca, Carla F Escobar-Tomlienovich, Davoneshia Lollis, Camila M Musso, Yiwei Mao, Abdull J Massri, Hannah M Doll, Andre M Sousa, Gregory A Wray, Ewoud Schmidt, Debra L Silver
Humans evolved an extraordinarily expanded and complex cerebral cortex, associated with developmental and gene regulatory modifications 1-3 . Human accelerated regions (HARs) are highly conserved genomic sequences with human-specific nucleotide substitutions. Although there are thousands of annotated HARs, their functional contribution to human-specific cortical development is largely unknown 4,5 . HARE5 is a HAR transcriptional enhancer of the WNT signaling receptor Frizzled8 (FZD8) active during brain development 6 ...
April 11, 2024: bioRxiv
#36
Fengyun Sun, Kathleen Desevin, Yu Fu, Shanmathi Parameswaran, Jemma Mayall, Vera Rinaldi, Nils Krietenstein, Artur Manukyan, Qiangzong Yin, Carolina Galan, Chih-Hsiang Yang, Anastasia V Shindyapina, Vadim N Gladyshev, Manuel Garber, John E Schjenken, Oliver J Rando
During mammalian reproduction, sperm are delivered to the female reproductive tract bathed in a complex medium known as seminal fluid, which plays key roles in signaling to the female reproductive tract and in nourishing sperm for their onwards journey. Along with minor contributions from the prostate and the epididymis, the majority of seminal fluid is produced by a somewhat understudied organ known as the seminal vesicle. Here, we report the first single-cell RNA-seq atlas of the mouse seminal vesicle, generated using tissues obtained from 23 mice of varying ages, exposed to a range of dietary challenges...
April 11, 2024: bioRxiv
#37
Ketaki A Katdare, Andrew Kjar, Natasha M O'Brown, Emma H Neal, Alexander G Sorets, Alena Shostak, Wilber Romero-Fernandez, Alexander J Kwiatkowski, Kate Mlouk, Hyosung Kim, Rebecca P Cowell, Katrina R Schwensen, Kensley B Horner, John T Wilson, Matthew S Schrag, Sean G Megason, Ethan S Lippmann
Brain endothelial cells (BECs) play an important role in maintaining central nervous system (CNS) homeostasis through blood-brain barrier (BBB) functions. BECs express low baseline levels of adhesion receptors, which limits entry of leukocytes. However, the molecular mediators governing this phenotype remain mostly unclear. Here, we explored how infiltration of immune cells across the BBB is influenced by the scaffold protein IQ motif containing GTPase activating protein 2 (IQGAP2). In mice and zebrafish, we demonstrate that loss of Iqgap2 increases infiltration of peripheral leukocytes into the CNS under homeostatic and inflammatory conditions...
April 12, 2024: bioRxiv
#38
George Butler, Sarah R Amend, Robert Axelrod, Chris Venditti, Kenneth J Pienta
The evolution of metastasis represents a lethal stage of cancer progression. Yet, the evolutionary kinetics of metastatic disease remain unresolved. Here, using single cell CRISPR-Cas9 lineage tracing data, we show that in metastatic disease, gradual molecular evolution is punctuated by episodes of rapid evolutionary change associated with lineage divergence. By measuring punctuational effects across the metastatic cascade, we show that punctuational effects contribute more to the molecular diversity at distal site metastases compared to the paired primary tumor, suggesting qualitatively different modes of evolution may drive primary and metastatic tumor progression...
April 11, 2024: bioRxiv
#39
Jacques Augenstreich, Anushka Poddar, Ashton T Belew, Najib M El-Sayed, Volker Briken
Time-lapse microscopy has emerged as a crucial tool in cell biology, facilitating a deeper understanding of dynamic cellular processes. While existing tracking tools have proven effective in detecting and monitoring objects over time, the quantification of signals within these tracked objects often faces implementation constraints. In the context of infectious diseases, the quantification of signals at localized compartments within the cell and around intracellular pathogens can provide even deeper insight into the interactions between the pathogen and host cell organelles...
April 11, 2024: bioRxiv
#40
Irina Kopyeva, Ethan C Goldner, Jack W Hoye, Shiyu Yang, Mary C Regier, Kaitlyn R Vera, Ross C Bretherton, Cole A DeForest
UNLABELLED: Biomechanical contributions of the ECM underpin cell growth and proliferation, differentiation, signal transduction, and other fate decisions. As such, biomaterials whose mechanics can be spatiotemporally altered - particularly in a reversible manner - are extremely valuable for studying these mechanobiological phenomena. Herein, we introduce a poly(ethylene glycol) (PEG)-based hydrogel model consisting of two interpenetrating step-growth networks that are independently formed via largely orthogonal bioorthogonal chemistries and sequentially degraded with distinct bacterial transpeptidases, affording reversibly tunable stiffness ranges that span healthy and diseased soft tissues (e...
April 8, 2024: bioRxiv
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