[ { "id": "https://authors.library.caltech.edu/records/dqnnv-knv04", "eprint_id": 122026, "eprint_status": "archive", "datestamp": "2023-08-20 16:49:52", "lastmod": "2023-12-22 23:39:45", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Prakash-Sharan-J", "name": { "family": "Prakash", "given": "Sharan J." }, "orcid": "0000-0003-1777-0987" }, { "id": "Van-Auken-Kimberly-M", "name": { "family": "Van Auken", "given": "Kimberly M." }, "orcid": "0000-0002-1706-4196" }, { "id": "Hill-D-P", "name": { "family": "Hill", "given": "David P." }, "orcid": "0000-0001-7476-6306" }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" } ] }, "title": "Semantic Representation of Neural Circuit Knowledge in Caenorhabditis elegans", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nWe thank all members of the Sternberg lab at Caltech for their feedback during the course of the project. We also thank Raymond Lee (WormBase) and members of the Gene Ontology Consortium, as well as Susan Bello (Mouse Genome Informatics) and members of the Unified Phenotype Ontology working group for helpful discussions. \n\nK.V.A. & D.P.H. are funded by the National Human Genome Research Institute (U24HG012212). S.J.P. is funded by NIH U24HG010859-03S2. \n\nData & Materials Availability. All data generated or analysed during this study are included in this published article (and its supplementary information files). \n\nThe authors declare that they have no competing interests.\n\n
Submitted - nihpp-2023.04.28.538760v1.pdf
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", "abstract": "In modern biology, new knowledge is generated quickly, making it challenging for researchers to efficiently acquire and synthesise new information from the large volume of primary publications. To address this problem, computational approaches that generate machine-readable representations of scientific findings in the form of knowledge graphs have been developed. These representations can integrate different types of experimental data from multiple papers and biological knowledge bases in a unifying data model, providing a complementary method to manual review for interacting with published knowledge. The Gene Ontology Consortium (GOC) has created a semantic modelling framework that extends individual functional gene annotations to structured descriptions of causal networks representing biological processes (Gene Ontology Causal Activity Modelling, or GO-CAM). In this study, we explored whether the GO-CAM framework could represent knowledge of the causal relationships between environmental inputs, neural circuits and behavior in the model nematode C. elegans (C. elegans Neural Circuit Causal Activity Modelling (CeN-CAM)). We found that, given extensions to several relevant ontologies, a wide variety of author statements from the literature about the neural circuit basis of egg-laying and carbon dioxide (CO2) avoidance behaviors could be faithfully represented with CeN-CAM. Through this process, we were able to generate generic data models for several categories of experimental results. We also generated representations of multisensory integration and sensory adaptation, and we discuss how semantic modelling may be used to functionally annotate the C. elegans connectome. Thus, Gene Ontology-based semantic modelling has the potential to support various machine-readable representations of neurobiological knowledge.", "date": "2023-06-29", "date_type": "published", "id_number": "CaltechAUTHORS:20230628-257134000.27", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230628-257134000.27", "funders": { "items": [ { "agency": "NIH", "grant_number": "U24HG012212" }, { "agency": "NIH", "grant_number": "U24HG010859-03S2" } ] }, "local_group": { "items": [ { "id": "Tianqiao-and-Chrissy-Chen-Institute-for-Neuroscience" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2023.04.28.538760", "pmcid": "PMC10168330", "primary_object": { "basename": "nihpp-2023.04.28.538760v1.pdf", "url": "https://authors.library.caltech.edu/records/dqnnv-knv04/files/nihpp-2023.04.28.538760v1.pdf" }, "related_objects": [ { "basename": "media-1.docx", "url": "https://authors.library.caltech.edu/records/dqnnv-knv04/files/media-1.docx" }, { "basename": "media-2.xlsx", "url": "https://authors.library.caltech.edu/records/dqnnv-knv04/files/media-2.xlsx" }, { "basename": "media-3.xlsx", "url": "https://authors.library.caltech.edu/records/dqnnv-knv04/files/media-3.xlsx" }, { "basename": "media-4.docx", "url": "https://authors.library.caltech.edu/records/dqnnv-knv04/files/media-4.docx" } ], "resource_type": "monograph", "pub_year": "2023", "author_list": "Prakash, Sharan J.; Van Auken, Kimberly M.; et el." }, { "id": "https://authors.library.caltech.edu/records/gmkyw-h0h31", "eprint_id": 120360, "eprint_status": "archive", "datestamp": "2023-08-20 08:30:34", "lastmod": "2023-12-13 17:16:04", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Brugman-Katherine-I", "name": { "family": "Brugman", "given": "Katherine I." }, "orcid": "0000-0003-2625-2903" }, { "id": "Susoy-Vladislav", "name": { "family": "Susoy", "given": "Vladislav" }, "orcid": "0000-0002-0669-0087" }, { "id": "Whittaker-Allyson-J", "name": { "family": "Whittaker", "given": "Allyson J." } }, { "id": "Palma-Wilber", "name": { "family": "Palma", "given": "Wilber" }, "orcid": "0000-0001-9382-9640" }, { "id": "Nava-Stephanie", "name": { "family": "Nava", "given": "Stephanie" }, "orcid": "0000-0002-5643-6693" }, { "id": "Samuel-Aravinthan-D-T", "name": { "family": "Samuel", "given": "Aravinthan D. T." }, "orcid": "0000-0002-1672-8720" }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" } ] }, "title": "PEZO-1 and TRP-4 mechanosensors are involved in mating behavior in Caenorhabditis elegans", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. \n\nWe thank WormBase for genome information, CGC for providing strains, Ian Kimbell for help with data collecting, Xiaofei Bai for providing AG570 pezo-1(av240), Shawn Xu for sharing a plasmid containing trp-4, and Tsui-Fen Chou for providing Cas9 protein. This work was supported by NIH R01-NS113119 (PWS and ADTS). KB was supported by NIH-Training Grant T32GM007616. \n\nThe authors have declared no competing interest.\n\nSubmitted - 2022.08.31.506045v1.full.pdf
", "abstract": "Male mating in Caenorhabditis elegans is a complex behavior with a strong mechanosensory component. C. elegans has several characterized mechanotransducer proteins, but few have been shown to contribute to mating. Here, we investigated the roles of PEZO-1, a piezo channel, and TRP-4, a mechanotransducing TRPN channel, in male mating behavior. We show that pezo-1 is expressed in several male-specific neurons with known roles in mating. We show that, among other neurons, trp-4 is expressed in the PCA sensory neuron, which monitors relative sliding between the male and the hermaphrodite and inhibits neurons involved in vulva detection. Mutations in both genes compromise many steps of mating, including initial response to the hermaphrodite, scanning, turning, and vulva detection. We performed pan-neuronal imaging during mating between freely-moving mutant males and hermaphrodites. Both pezo-1 and trp-4 mutants showed spurious activation of the sensory neurons involved in vulva detection. In trp-4 mutants, this spurious activation might be caused by PCA failure to inhibit vulva-detecting neurons during scanning. Indeed, we show that without functional TRP-4, PCA fails to detect the relative sliding between the male and hermaphrodite. Cell-specific TRP-4 expression restores PCA's mechanosensory function. Our results demonstrate new roles for both PEZO-1 and TRP-4 mechanotransducers in C. elegans mating behavior.", "date": "2023-03-26", "date_type": "published", "id_number": "CaltechAUTHORS:20230323-69637000.1", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230323-69637000.1", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 NS113119" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32GM007616" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.08.31.506045", "primary_object": { "basename": "2022.08.31.506045v1.full.pdf", "url": "https://authors.library.caltech.edu/records/gmkyw-h0h31/files/2022.08.31.506045v1.full.pdf" }, "resource_type": "monograph", "pub_year": "2023", "author_list": "Brugman, Katherine I.; Susoy, Vladislav; et el." }, { "id": "https://authors.library.caltech.edu/records/t3k1f-dtw80", "eprint_id": 120139, "eprint_status": "archive", "datestamp": "2023-08-20 09:07:12", "lastmod": "2023-12-13 17:18:00", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Tan-Chieh-Hsiang", "name": { "family": "Tan", "given": "Chieh-Hsiang" }, "orcid": "0000-0002-5432-0160" }, { "id": "Cheng-Kai-Wen", "name": { "family": "Cheng", "given": "Kai-Wen" }, "orcid": "0000-0001-9888-9773" }, { "id": "Park-Heenam", "name": { "family": "Park", "given": "Heenam" }, "orcid": "0000-0001-7911-5828" }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" }, { "id": "Chou-Tsui-Fen", "name": { "family": "Chou", "given": "Tsui-Fen" }, "orcid": "0000-0003-2410-2186" } ] }, "title": "LINKIN-associated proteins necessary for tissue integrity during collective cell migration", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nWe thank Barbara Perry, Wilber Palma and Stephanie Nava for laboratory assistance. We thank members of our laboratory for discussions. Mutant alleles- mvk-1(tm6628), trd-1(tm2764), vha-19(tm2225), prx-3(tm6469), and rod-1(tm6186) were provided by the MITANI Lab through the National Bio-Resource Project of the MEXT, Japan. Some strains were obtained from the Caenorhabditis Genetics Center (CGC), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). This work was also facilitated by WormBase, a knowledgebase for nematode research; and by the Alliance of Genome Resources, a research platform that facilitates cross species research, This research was supported by NIH R01HD086596 (PWS and TFC), R01HD091327 (PWS), and R24 0D023041 (PWS). \n\nThe authors have declared no competing interest.\n\nSubmitted - 2023.02.08.527750v1.full.pdf
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", "abstract": "Cell adhesion plays essential roles in almost every aspect of metazoan biology. Previously, using the developmental migration of the nematode male gonad as a platform, LINKIN (Human: ITFG1,C. elegans: lnkn-1), a relatively understudied transmembrane protein conserved across the metazoa, was found to be necessary for tissue integrity during migration. InC. elegans, loss of lnkn-1 results in the detachment of the lead migratory cell from the rest of the developing male gonad. Three interactors of ITFG1/lnkn-1-RUVBL1/ruvb-1, RUVBL2/ruvb-2, and alpha-tubulin were identified by proteomic analysis using the human HEK293T cells and validated in the nematode male gonad. The ITFG1-RUVBL1 interaction has since been independently validated in a breast cancer cell line model that also implicates the involvement of the pair in metastasis. In this study, we showed that epitope-tagged ITFG1 localized to the cell surface of MDA-MB-231 breast cancer cells. Using unbiased mass spectrometry-based proteomics, we identified a new list of potential interactors of ITFG1. Loss-of-function analysis of their C. elegans orthologs found that three of the interactors - ATP9A/tat-5, NME1/ndk-1, and ANAPC2/apc-2 displayed migratory detachment phenotypes similar to that of lnkn-1. Taken together with the other genes whose reduction of function phenotype is the same as LINKIN (notably cohesion and condensin) suggests the involvement of membrane remodeling and chromosome biology in the tight adhesion dependent on LINKIN, and support the hypothesis for a structure role of chromosomes in post-mitotic cells.", "date": "2023-03-21", "date_type": "published", "id_number": "CaltechAUTHORS:20230316-182235000.22", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230316-182235000.22", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education, Culture, Sports, Science and Technology (MEXT)" }, { "agency": "NIH", "grant_number": "P40 OD010440" }, { "agency": "NIH", "grant_number": "R01HD086596" }, { "agency": "NIH", "grant_number": "R01HD091327" }, { "agency": "NIH", "grant_number": "R24 0D023041" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2023.02.08.527750", "primary_object": { "basename": "media-3.xlsx", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/media-3.xlsx" }, "related_objects": [ { "basename": "media-4.xlsx", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/media-4.xlsx" }, { "basename": "media-5.docx", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/media-5.docx" }, { "basename": "media-6.docx", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/media-6.docx" }, { "basename": "2023.02.08.527750v1.full.pdf", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/2023.02.08.527750v1.full.pdf" }, { "basename": "media-1.xlsx", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/media-1.xlsx" }, { "basename": "media-2.xlsx", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/media-2.xlsx" } ], "resource_type": "monograph", "pub_year": "2023", "author_list": "Tan, Chieh-Hsiang; Cheng, Kai-Wen; et el." }, { "id": "https://authors.library.caltech.edu/records/d3h3d-ctj75", "eprint_id": 115810, "eprint_status": "archive", "datestamp": "2023-08-20 08:15:24", "lastmod": "2023-12-13 17:17:38", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Truong-Lisa", "name": { "family": "Truong", "given": "Lisa" } }, { "id": "Chen-Yen-Wei", "name": { "family": "Chen", "given": "Yen-Wei" } }, { "id": "Barrere-Cain-Rio", "name": { "family": "Barrere-Cain", "given": "Rio" }, "orcid": "0000-0002-0522-253X" }, { "id": "Shuck-Karissa", "name": { "family": "Shuck", "given": "Karissa" } }, { "id": "Xiao-Wen", "name": { "family": "Xiao", "given": "Wen" }, "orcid": "0000-0001-6559-3036" }, { "id": "Levenson-Max-T", "name": { "family": "Levenson", "given": "Max T." }, "orcid": "0000-0002-1470-3968" }, { "id": "da-Veiga-Beltrame-Eduardo", "name": { "family": "da Veiga Beltrame", "given": "Eduardo" }, "orcid": "0000-0002-1529-9207" }, { "id": "Panter-Blake", "name": { "family": "Panter", "given": "Blake" } }, { "id": "Reich-Ella", "name": { "family": "Reich", "given": "Ella" } }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" }, { "id": "Yang-Xia", "name": { "family": "Yang", "given": "Xia" } }, { "id": "Allard-Patrick", "name": { "family": "Allard", "given": "Patrick" }, "orcid": "0000-0001-7765-1547" } ] }, "title": "Single-nucleus resolution mapping of the adult C. elegans and its application to elucidate inter- and trans-generational response to alcohol", "ispublished": "unpub", "full_text_status": "public", "keywords": "C. elegans, snRNA-seq, ethanol, alcohol", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. \n\nThe authors would like to thank Doug Arneson for input on single-nucleus sequencing parameters; Ingrid Cely, In Sook Ahn, and Graciel Diamante for discussions and trouble-shooting advice; Eyal Ben David for advice on single-cell/nuclei dissociation methods; Jessica Scholes, Jeffrey Calim, Felicia Codrea, and Salem Haile for guidance with single-nucleus cytometry; Michael Mashock and Marco De Simone for their library preparation and sequencing expertise. Matteo Pellegrini for advice and input on data analysis. We thank Judith Kimble, Tina Lynch, and Sarah Crittenden for advice on smFISH and providing the sygl-1 probe. The Caenorhabditis Genetics Center (CGC) provided the strains used in this study. We thank Yuji Kohara for permission to use NEXTDB in situ data. \n\nLT is supported by the NIH Training Grant in Genomic Analysis and Interpretation T32 HG002536; YWC is supported by the UCLA Eureka fellowship and Burroughs Wellcome Fund Inter-school Training Program in Chronic Diseases; PA is supported by NIEHS R01 ES027487, NIAAA R21 AA024889, the John Templeton Foundation, and the Burroughs Wellcome Innovation in Regulatory Science Award. EDVB and PWS are supported by U24HG002223. \n\nAuthor Contributions. LT, RBC, KS, WX, MTL, BP, and EL performed biological experiments and corresponding analyses, YWC performed bioinformatic analyses, PA and XY supervised experiments, PA and XY supervised analyses, EB devised a visualization approach that assisted cell type assignment and cluster identification which PS supervised, LT, RBC, YWC, XY, and PA wrote the manuscript. \n\nDATA AVAILABILITY. All raw data is accessible on NCBI's Gene Expression Omnibus (GEO), at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE208229\n\nThe data is also available through the Broad Single Cell Portal: \n\nhttps://singlecell.broadinstitute.org/single_cell/study/SCP922/single-nucleus-resolution-mapping-of-the-adult-c-elegans-and-its-application-to-elucidate-inter-and-transgenerational-response-to-alcohol\n\nThe authors have declared no competing interest.\n\nSubmitted - 2022.07.21.500524v1.full.pdf
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", "abstract": "Single-cell RNA transcriptomic platforms have significantly contributed to our understanding of tissue heterogeneity as well as of developmental and cellular differentiation trajectories. They also provide an opportunity to map an organism's response to environmental cues with high resolution and unbiasedly identify the cell types that are the most transcriptionally sensitive to exposures. Here, we applied single nucleus RNA-seq experimental and computational approaches to C. elegans to establish the transcriptome of the adult nematode and comprehensively characterize the transcriptional impact of ethanol as a model environmental exposure on the entire organism at cell type-resolution over several generations. Clustering, tissue and phenotype enrichment, and gene ontology analyses identified 31 clusters representing a diverse number of adult cell types, including those from syncytial and multi-nucleated tissues which are difficult to assess by single cell RNA-seq, such as the mitotic and meiotic germline, hypodermal cells, and the intestine. We applied this method to identify the impact of inter- and trans-generational exposure to two human-relevant doses of alcohol. Cell type proportions were not significantly altered by ethanol. However, Euclidean distance analysis identified several germline, striated muscle, and neuronal clusters as being major transcriptional targets of ethanol at both the F1 and F3 generations although the relative order of clusters changed between generations. The impact on germline clusters was further confirmed by phenotypic enrichment analysis as well as functional validation, namely a remarkable inter- and trans-generational increase in germline apoptosis, aneuploidy, and embryonic lethality. Together, snRNA-seq of the adult C. elegans represents a powerful approach for the detailed examination of an adult organism's response to environmental cues.", "date": "2022-07-27", "date_type": "published", "id_number": "CaltechAUTHORS:20220725-414617000", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220725-414617000", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32 HG002536" }, { "agency": "UCLA" }, { "agency": "Burroughs Wellcome Fund" }, { "agency": "NIH", "grant_number": "R01 ES027487" }, { "agency": "NIH", "grant_number": "R21 AA024889" }, { "agency": "John Templeton Foundation" }, { "agency": "NIH", "grant_number": "U24HG002223" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.07.21.500524", "primary_object": { "basename": "2022.07.21.500524v1.full.pdf", "url": "https://authors.library.caltech.edu/records/d3h3d-ctj75/files/2022.07.21.500524v1.full.pdf" }, "related_objects": [ { "basename": "media-6.csv", "url": "https://authors.library.caltech.edu/records/d3h3d-ctj75/files/media-6.csv" }, { "basename": "media-8.xlsx", "url": "https://authors.library.caltech.edu/records/d3h3d-ctj75/files/media-8.xlsx" }, { "basename": "media-4.xlsx", "url": "https://authors.library.caltech.edu/records/d3h3d-ctj75/files/media-4.xlsx" }, { "basename": "media-5.xlsx", "url": "https://authors.library.caltech.edu/records/d3h3d-ctj75/files/media-5.xlsx" }, { "basename": "media-7.xlsx", "url": "https://authors.library.caltech.edu/records/d3h3d-ctj75/files/media-7.xlsx" }, { "basename": "media-1.docx", "url": "https://authors.library.caltech.edu/records/d3h3d-ctj75/files/media-1.docx" }, { "basename": "media-2.pdf", "url": "https://authors.library.caltech.edu/records/d3h3d-ctj75/files/media-2.pdf" }, { "basename": "media-3.xlsx", "url": "https://authors.library.caltech.edu/records/d3h3d-ctj75/files/media-3.xlsx" } ], "resource_type": "monograph", "pub_year": "2022", "author_list": "Truong, Lisa; Chen, Yen-Wei; et el." }, { "id": "https://authors.library.caltech.edu/records/qhpqv-6t471", "eprint_id": 111706, "eprint_status": "archive", "datestamp": "2023-08-20 05:44:44", "lastmod": "2023-12-13 17:17:19", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Reilly-Douglas-K", "name": { "family": "Reilly", "given": "Douglas K." }, "orcid": "0000-0001-8260-8690" }, { "id": "Schwarz-Erich-M", "name": { "family": "Schwarz", "given": "Erich M." }, "orcid": "0000-0003-3151-4381" }, { "id": "Muirhead-Caroline-S", "name": { "family": "Muirhead", "given": "Caroline S." } }, { "id": "Robidoux-Annalise-N", "name": { "family": "Robidoux", "given": "Annalise N." } }, { "id": "Antoshechkin-Igor-A", "name": { "family": "Antoshechkin", "given": "Igor" }, "orcid": "0000-0002-9934-3040" }, { "id": "Narayan-Anusha", "name": { "family": "Narayan", "given": "Anusha" } }, { "id": "Doma-Meenakshi-K", "name": { "family": "Doma", "given": "Meenakshi K." } }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" }, { "id": "Srinivasan-Jagan", "name": { "family": "Srinivasan", "given": "Jagan" }, "orcid": "0000-0001-5449-7938" } ] }, "title": "Transcriptomic profiling of sex-specific olfactory neurons reveals subset-specific receptor expression in C. elegans", "ispublished": "unpub", "full_text_status": "public", "keywords": "C. elegans, Pheromone, Sex-specific, G Protein-Coupled Receptors, Transcriptomes, Single-Cell", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. \n\nWe thank the Caenorhabditis Genetics Center, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD01044), as well as the National BioResource Project, Ding Xue (University of Colorado, Boulder), L. Rene Garcia (Texas A&M University), and Douglas Portman (University of Rochester Medical Center) for providing strains. We also thank Igor Antoshechkin, Caltech Genomics facility for sequencing and InVivo Biosystems for generating transgenic and CRISPR knockout animals. The synthetic ascr#8 utilized in this study was provided by Frank Schroeder (Cornell University). The research reported in this publication was supported by NIH R01 DC016058 (J.S.), R01 GM084389 (P.W.S.), the Howard Hughes Medical Institute (P.W.S.), Moore Foundation Grant No. 4551 (E.M.S.), and Cornell startup funding (E.M.S.). We thank Titus Brown and the Michigan State University High-Performance Computing Center (supported by U.S. Department of Agriculture grant 2010-65205-20361 and NIFA\u2013National Science Foundation (NSF) grant IOS-0923812) for computational support; additional computing was enabled by start-up and research allocations from NSF XSEDE (TG538 MCB180039 and TG-MCB190010). \n\nData availability: RNA-seq reads have been deposited in the NCBI Sequence Read Archive (SRA) under the BioProject accession number PRJNA781271. \n\nThe authors have declared no competing interest.\n\nSubmitted - 2021.10.26.465928v2.full.pdf
Supplemental Material - media-1.pdf
Supplemental Material - media-2.xlsx
Supplemental Material - media-3.xlsx
Supplemental Material - media-4.xlsx
", "abstract": "The nematode Caenorhabditis elegans utilizes chemosensation to navigate an ever-changing environment for its survival. A class of secreted small-molecule pheromones, termed ascarosides, play an important role in olfactory perception by affecting biological functions ranging from development to behavior. The ascaroside ascr#8 mediates sex-specific behaviors, driving avoidance in hermaphrodites and attraction in males. Males sense ascr#8 via the ciliated male-specific cephalic sensory (CEM) neurons, which exhibit radial symmetry along dorsal-ventral and left-right axes. Calcium imaging studies suggest a complex neural coding mechanism that translates stochastic physiological responses in these neurons to reliable behavioral outputs. To test the hypothesis that neurophysiological complexity arises from differential expression of genes, we performed cell-specific transcriptomic profiling; this revealed between 18 and 62 genes with at least two-fold higher expression in a specific CEM neuron type versus both other CEM neurons and adult males. These included two G protein coupled receptor (GPCR) genes, srw-97 and dmsr-12, that were specifically expressed in non-overlapping subsets of CEM neurons and whose expression was confirmed by GFP reporter analysis. Single CRISPR-Cas9 knockouts of either srw-97 or dmsr-12 resulted in partial defects, while a double knockout of both srw-97 and dmsr-12 completely abolished the attractive response to ascr#8. Together, our results suggest that the evolutionarily distinct GPCRs SRW-97 and DMSR-12 act non-redundantly in discrete olfactory neurons to facilitate male-specific sensation of ascr#8.", "date": "2021-11-02", "date_type": "published", "id_number": "CaltechAUTHORS:20211102-173632613", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211102-173632613", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "P40 OD010440" }, { "agency": "NIH", "grant_number": "R01 DC016058" }, { "agency": "NIH", "grant_number": "R01 GM084389" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Gordon and Betty Moore Foundation", "grant_number": "4551" }, { "agency": "Cornell University" }, { "agency": "Department of Agriculture", "grant_number": "2010-65205-20361" }, { "agency": "NSF", "grant_number": "IOS-0923812" }, { "agency": "NSF", "grant_number": "TG538 MCB180039" }, { "agency": "NSF", "grant_number": "TG-MCB190010" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2021.10.26.465928", "primary_object": { "basename": "media-2.xlsx", "url": "https://authors.library.caltech.edu/records/qhpqv-6t471/files/media-2.xlsx" }, "related_objects": [ { "basename": "media-3.xlsx", "url": "https://authors.library.caltech.edu/records/qhpqv-6t471/files/media-3.xlsx" }, { "basename": "media-4.xlsx", "url": "https://authors.library.caltech.edu/records/qhpqv-6t471/files/media-4.xlsx" }, { "basename": "2021.10.26.465928v2.full.pdf", "url": "https://authors.library.caltech.edu/records/qhpqv-6t471/files/2021.10.26.465928v2.full.pdf" }, { "basename": "media-1.pdf", "url": "https://authors.library.caltech.edu/records/qhpqv-6t471/files/media-1.pdf" } ], "resource_type": "monograph", "pub_year": "2021", "author_list": "Reilly, Douglas K.; Schwarz, Erich M.; et el." }, { "id": "https://authors.library.caltech.edu/records/p1prv-6ds73", "eprint_id": 110355, "eprint_status": "archive", "datestamp": "2023-08-20 04:43:48", "lastmod": "2023-12-13 17:16:58", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Banerjee-Navonil", "name": { "family": "Banerjee", "given": "Navonil" } }, { "id": "Shih-Pei-Yin", "name": { "family": "Shih", "given": "Pei-Yin" }, "orcid": "0000-0003-3082-9242" }, { "id": "Rojas-Palato-Elisa-J", "name": { "family": "Rojas Palato", "given": "Elisa J." } }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" }, { "id": "Hallem-Elissa-A", "name": { "family": "Hallem", "given": "Elissa A." }, "orcid": "0000-0003-0260-3174" } ] }, "title": "Distinct neural circuits establish the same chemosensory behavior in C. elegans", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. \n\nThis version posted August 17, 2021. \n\nWe thank the Caenorhabditis Genetics Centre, the C. elegans Knockout Consortium, Oliver Hobert, Cori Bargmann, Gary Ruvkun, Shai Shaham, Ikue Mori, Yuichi Iino, and Mario de Bono for strains. We thank Astra Bryant, Michelle Castelletto, and Ricardo Frausto for insightful comments on the manuscript. This work was funded by NIH F32 AI147617 (N.B.), NIH MARC T34 GM008563 (E.R.P.), NIH UF1 NS111697 (P.W.S.), and NIH R01 DC017959 and an HHMI Faculty Scholar Award (E.A.H.). \n\nAuthor Contributions: N.B., P.-Y.S., P.W.S., and E.A.H. conceived the study. N.B. and E.R.P. performed experiments. N.B. and E.R.P. analyzed the data. N.B., E.R.P., and E.A.H. wrote the manuscript. All authors read and approved the final manuscript. \n\nThe authors declare no competing interests.\n\nSubmitted - 2021.08.17.456617v1.full.pdf
", "abstract": "Animals frequently exhibit the same behavior under different environmental or physiological conditions. To what extent these behaviors are generated by similar vs. distinct mechanisms is unclear. Moreover, the circumstances under which divergent neural mechanisms establish the same behavior, and the molecular signals that regulate the same behavior across conditions, are poorly understood. We show that in C. elegans, distinct neural mechanisms mediate the same chemosensory behavior at two different life stages. Both dauer larvae and starved adults are attracted to carbon dioxide (CO\u2082), but CO\u2082 attraction is mediated by distinct sets of interneurons at the two life stages. Some interneurons mediate CO\u2082 response only in dauers, some show CO2-evoked activity in adults and dauers but contribute to CO\u2082 response only in adults, and some show CO\u2082-evoked activity that opposes CO\u2082 attraction in adults but promotes CO\u2082 attraction in dauers. We also identify a novel role for insulin signaling in establishing life-stage-specific CO\u2082 responses by modulating interneuron activity. Further, we show that a combinatorial code of both shared and life-stage-specific molecular signals regulate CO\u2082 attraction. Our results identify a mechanism by which the same chemosensory behavior can be generated by distinct neural circuits, revealing an unexpected complexity to chemosensory processing.", "date": "2021-08-21", "date_type": "published", "id_number": "CaltechAUTHORS:20210821-151507927", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210821-151507927", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32 AI147617" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "T34 GM008563" }, { "agency": "NIH", "grant_number": "UF1 NS111697" }, { "agency": "NIH", "grant_number": "R01 DC017959" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2021.08.17.456617", "primary_object": { "basename": "2021.08.17.456617v1.full.pdf", "url": "https://authors.library.caltech.edu/records/p1prv-6ds73/files/2021.08.17.456617v1.full.pdf" }, "resource_type": "monograph", "pub_year": "2021", "author_list": "Banerjee, Navonil; Shih, Pei-Yin; et el." }, { "id": "https://authors.library.caltech.edu/records/172k7-01k12", "eprint_id": 109773, "eprint_status": "archive", "datestamp": "2023-08-20 04:09:39", "lastmod": "2023-12-22 23:30:53", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "da-Veiga-Beltrame-Eduardo", "name": { "family": "da Veiga Beltrame", "given": "Eduardo" }, "orcid": "0000-0002-1529-9207" }, { "id": "Arnaboldi-Valerio", "name": { "family": "Arnaboldi", "given": "Valerio" }, "orcid": "0000-0002-2563-5374" }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" } ] }, "title": "Single cell tools for WormBase", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder has placed this preprint in the Public Domain. It is no longer restricted by copyright. Anyone can legally share, reuse, remix, or adapt this material for any purpose without crediting the original authors. \n\nThis version posted July 4, 2021. \n\nThe authors would like to thank Paulo Nuin for reviewing the code, Tom Morrell for assistance with CaltechData, and Valentine Svensson for suggestions on the manuscript. This work was supported by grants NIH U24HG010859 and NIH U24HG002223.\n\nSubmitted - 2021.07.04.451030v1.full.pdf
", "abstract": "We present two web apps for interactively performing common tasks with single cell RNA sequencing data: scdefg for interactive differential expression and wormcells-viz for visualization of gene expression. We made these tools available with public C. elegans datasets curated by WormBase at single-cell.wormbase.org. They can also be readily deployed for use with any other datasets using the source code available at github.com/WormBase/scdefg and at github.com/WormBase/wormcells-viz.", "date": "2021-07-12", "date_type": "published", "id_number": "CaltechAUTHORS:20210712-143510822", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210712-143510822", "funders": { "items": [ { "agency": "NIH", "grant_number": "U24HG010859" }, { "agency": "NIH", "grant_number": "U24HG002223" } ] }, "local_group": { "items": [ { "id": "WormBase" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2021.07.04.451030", "primary_object": { "basename": "2021.07.04.451030v1.full.pdf", "url": "https://authors.library.caltech.edu/records/172k7-01k12/files/2021.07.04.451030v1.full.pdf" }, "resource_type": "monograph", "pub_year": "2021", "author_list": "da Veiga Beltrame, Eduardo; Arnaboldi, Valerio; et el." }, { "id": "https://authors.library.caltech.edu/records/cfdy6-q9489", "eprint_id": 105100, "eprint_status": "archive", "datestamp": "2023-08-19 23:01:52", "lastmod": "2023-12-13 17:16:12", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Le-Henry-H", "name": { "family": "Le", "given": "Henry H." }, "orcid": "0000-0003-2942-2357" }, { "id": "Wrobel-C-J", "name": { "family": "Wrobel", "given": "Chester J." }, "orcid": "0000-0001-6047-4644" }, { "id": "Cohen-S-M", "name": { "family": "Cohen", "given": "Sarah M." }, "orcid": "0000-0002-5233-2280" }, { "id": "Yu-Jingfang", "name": { "family": "Yu", "given": "Jingfang" }, "orcid": "0000-0003-1770-5368" }, { "id": "Park-Heenam", "name": { "family": "Park", "given": "Heenam" }, "orcid": "0000-0001-7911-5828" }, { "id": "Helf-M-J", "name": { "family": "Helf", "given": "Maximilian J." }, "orcid": "0000-0002-1393-3999" }, { "id": "Curtis-B-J", "name": { "family": "Curtis", "given": "Brian J." } }, { "id": "Rodrigues-P-R", "name": { "family": "Rodrigues", "given": "Pedro R." } }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" }, { "id": "Schroeder-F-C", "name": { "family": "Schroeder", "given": "Frank C." }, "orcid": "0000-0002-4420-0237" } ] }, "title": "Modular metabolite assembly in C. elegans lysosome-related organelles", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. \n\nPosted August 24, 2020. \n\nThis research was funded by an NIH Chemical Biology Interface (CBI) Training Grant 5T32GM008500 (to B.C.), National Institutes of Health grants R35 GM131877 (to F.C.S.), and R24OD023041 (to P.W.S.). F.C.S. is a Faculty Scholar of the Howard Hughes Medical Institute. We thank WormBase for sequences, Tsui-Fen Chou for Cas9 protein, Ying (Kitty) Zhang for assistance with NMR spectroscopy, and Navid Movahed for assistance with mass spectrometry. \n\nAuthor Contributions: The manuscript was written through contributions of all authors and all authors have given approval to the final version of the manuscript. \n\nThe authors declare no competing interests.\n\nSubmitted - 2020.08.22.262956v1.full.pdf
", "abstract": "Signaling molecules derived from attachment of diverse primary metabolic building blocks to ascarosides play a central role in the life history of C. elegans and other nematodes; however, many aspects of their biogenesis remain unclear. Using comparative metabolomics, we show that lysosome-related organelles (LROs) are required for biosynthesis of most modular ascarosides as well as previously undescribed modular glucosides. Both modular glucosides and ascarosides are derived from highly selective assembly of moieties from nucleoside, amino acid, neurotransmitter, and lipid metabolism. We further show that cholinesterase (cest) homologs that localize to the LROs are required for assembly of both modular ascarosides and glucosides, mediating formation of ester and amide linkages between subsets of building blocks. Their specific biosynthesis suggests that modular glucosides, like ascarosides, serve dedicated signaling functions. Further exploration of LRO function and cest homologs in C. elegans and other animals may reveal additional new compound families and signaling paradigms.", "date": "2020-08-25", "date_type": "published", "id_number": "CaltechAUTHORS:20200825-103646907", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200825-103646907", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Predoctoral Fellowship", "grant_number": "5T32GM008500" }, { "agency": "NIH", "grant_number": "R35 GM131877" }, { "agency": "NIH", "grant_number": "R24OD023041" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2020.08.22.262956", "primary_object": { "basename": "2020.08.22.262956v1.full.pdf", "url": "https://authors.library.caltech.edu/records/cfdy6-q9489/files/2020.08.22.262956v1.full.pdf" }, "resource_type": "monograph", "pub_year": "2020", "author_list": "Le, Henry H.; Wrobel, Chester J.; et el." }, { "id": "https://authors.library.caltech.edu/records/mzz80-z1b49", "eprint_id": 26098, "eprint_status": "archive", "datestamp": "2023-08-19 15:20:56", "lastmod": "2023-10-24 16:13:59", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Cronin-C-J", "name": { "family": "Cronin", "given": "Christopher J." } }, { "id": "Mendel-J-E", "name": { "family": "Mendel", "given": "Jane E." } }, { "id": "Mukhtar-S", "name": { "family": "Mukhtar", "given": "Saleem" } }, { "id": "Kim-Y-M", "name": { "family": "Kim", "given": "Young-Mee" } }, { "id": "Stirbl-R-C", "name": { "family": "Stirbl", "given": "Robert C." } }, { "id": "Bruck-J", "name": { "family": "Bruck", "given": "Jehoshua" }, "orcid": "0000-0001-8474-0812" }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" } ] }, "title": "An automated system for measuring parameters of nematode sinusoidal movement", "ispublished": "unpub", "full_text_status": "public", "note": "Availability of source code \nSource code is available through a GPL at http://wormlab.caltech.edu/publications/download.html\nDocumentation of this software is available as a pdf from\nhttp://wormlab.caltech.edu/publications/download.html\n\nContributions of authors \nSM, JB, JM and PS conceived and designed the original\nautomated system for tracking and movement measurement.\nSM developed a working prototype system and brought in the key algorithms used. CC wrote most of the code in the current release. JM developed the protocol for the plate assay, and devised the dose-response and genetic experiments. RS conceived of applying automated analysis\nof C. elegans movement for toxicology studies, YK performed\nmost of the toxicology experiments. JM, CC, RS and PS analyzed the data. CC, JM, and PS wrote the paper. All authors read and approved the final manuscript. \n\nAcknowledgements \nWe thank X. Xu for suggesting length normalization, Jonathan Shewchuk for Triangle, and anonymous reviewers for many helpful suggestions. Supported by grants from the ONR (S.B.), DARPA (R. S.) and Howard Hughes Medical Institute, with which PWS is an Investigator. \n\nhttp://www.paradise.caltech.edu/papers/etr066.pdf", "abstract": "Background: Nematode sinusoidal movement has been used as a phenotype in many studies of C. elegans development, behavior and physiology. A thorough understanding of the ways in which genes control these aspects of biology depends, in part, on the accuracy of phenotypic analysis. While worms that move poorly are relatively easy to describe, description of hyperactive movement and movement modulation presents more of a challenge. An enhanced capability to analyze all the complexities of nematode movement will thus help our understanding of how genes control behavior.\n\nResults: We have developed a user-friendly system to analyze nematode movement in an automated and quantitative manner. In this system nematodes are automatically recognized and a computer-controlled microscope stage ensures that the nematode is kept within the camera field of view while video images from the camera are stored on videotape. In a second step, the images from the videotapes are processed to recognize the worm and to extract its changing position and posture over time. From this information, a variety of movement parameters are calculated. These parameters include the velocity of the worm's centroid, the velocity of the worm along its track, the extent and frequency of body bending, the amplitude and wavelength of the sinusoidal movement, and the propagation of the contraction wave along the body. The length of the worm is also determined and used to normalize the amplitude and wavelength measurements. \n\nTo demonstrate the utility of this system, we report here a comparison of movement parameters for a small set of mutants\naffecting the Go/Gq mediated signaling network that controls acetylcholine release at the neuromuscular junction. The system allows comparison of distinct genotypes that affect movement similarly (activation of Gq-alpha versus loss of Go-alpha function), as well as of different mutant alleles at a single locus (null and dominant negative alleles of the goa-1 gene, which encodes Goalpha). We also demonstrate the use of this system for analyzing the effects of toxic agents. Concentration-response curves for the toxicants arsenite and aldicarb, both of which affect motility, were determined for wild-type and several mutant strains,\nidentifying P-glycoprotein mutants as not significantly more sensitive to either compound, while cat-4 mutants are more sensitive to arsenite but not aldicarb.\n\nConclusions: Automated analysis of nematode movement facilitates a broad spectrum of experiments. Detailed genetic analysis of multiple alleles and of distinct genes in a regulatory network is now possible. These studies will facilitate quantitative modeling of C. elegans movement, as well as a comparison of gene function. Concentration-response curves will allow rigorous analysis\nof toxic agents as well as of pharmacological agents. This type of system thus represents a powerful analytical tool that can be readily coupled with the molecular genetics of nematodes.", "date": "2005-02-07", "date_type": "published", "publisher": "California Institute of Technology", "id_number": "CaltechPARADISE:2005.ETR066", "official_url": "https://resolver.caltech.edu/CaltechPARADISE:2005.ETR066", "rights": "You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format.", "local_group": { "items": [ { "id": "Parallel-and-Distributed-Systems-Group" } ] }, "primary_object": { "basename": "etr066.pdf", "url": "https://authors.library.caltech.edu/records/mzz80-z1b49/files/etr066.pdf" }, "resource_type": "monograph", "pub_year": "2005", "author_list": "Cronin, Christopher J.; Mendel, Jane E.; et el." } ]