bioRxiv : the preprint server for biology最新文献

{"title":"A Bioluminescent Activity Dependent (BLADe) Platform for Converting Intracellular Activity to Photoreceptor Activation.","authors":"Emmanuel L Crespo, Akash Pal, Mansi Prakash, Alexander D Silvagnoli, Zohair Zaidi, Manuel Gomez-Ramirez, Maya O Tree, Nathan C Shaner, Diane Lipscombe, Christopher I Moore, Ute Hochgeschwender","doi":"10.1101/2023.06.25.546469","DOIUrl":"10.1101/2023.06.25.546469","url":null,"abstract":"<p><p>Genetically encoded sensors and actuators have advanced the ability to observe and manipulate cellular activity, yet few non-invasive strategies enable cells to directly couple their intracellular states to user-defined outputs. We developed a bioluminescent activity-dependent (BLADe) platform that facilitates programmable feedback through genetically encoded light generation. Using calcium (Ca2+) flux as a model, we engineered a Ca2+-dependent luciferase that functions as both a reporter and an activity-gated light source capable of photoactivating light-sensing actuators. In neurons, the presence of luciferin triggers Ca2+ dependent local illumination that provides activity dependent gene expression by activating a light-sensitive transcription factor and control of neural dynamics through opsin activation in single cells, populations and intact tissue. BLADe can be expanded to couple any signal that bioluminescent enzymes can be engineered to detect with the wide variety of photosensing actuators. This modular strategy of coupling an activity dependent light emitter to a light sensing actuator offers a generalizable framework for state dependent cell-autonomous control across biological systems.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/2a/nihpp-2023.06.25.546469v1.PMC10327117.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10664894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell autonomous polarization by the planar cell polarity signaling pathway.","authors":"Alexis T Weiner, Silas Boye Nissen, Kaye L Suyama, Bomsoo Cho, Gandhy Pierre-Louis, Jeffrey D Axelrod","doi":"10.1101/2023.09.26.559449","DOIUrl":"10.1101/2023.09.26.559449","url":null,"abstract":"<p><p>Planar Cell Polarity (PCP) signaling polarizes epithelial cells in a plane orthogonal to their apical-basal axis. A core PCP signaling module both generates molecular asymmetry within cells and coordinates the direction of polarization between neighboring cells. Two subcomplexes of core proteins segregate to opposite sides of the cell, defining a polarity axis. Homodimers of the atypical cadherin Flamingo are thought to be the scaffold upon which these subcomplexes assemble and are required for intercellular polarity signaling. The central role for Flamingo homodimers in scaffolding and intercellular communication suggests that cells in which intercellular signaling via Flamingo is disabled should fail to polarize. We show that cells lacking Flamingo, or bearing a truncated Flamingo that cannot homodimerize do in fact polarize. Cell polarization requires both positive and negative feedback, and in a multicellular tissue, feedback might involve both intracellular and intercellular pathways. We identify positive and negative feedback pathways that operate cell autonomously to drive polarization.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bc/3e/nihpp-2023.09.26.559449v1.PMC10557733.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptin antagonism improves Rett syndrome phenotype in symptomatic Mecp2-deficient mice.","authors":"Yasmine Belaidouni, Diabe Diabira, Pascal Salin, Melanie Brosset-Heckel, Victoria Valsamides, Jean-Charles Graziano, Catarina Santos, Clement Menuet, Gary Wayman, Jean-Luc Gaiarsa","doi":"10.1101/2023.02.03.526251","DOIUrl":"10.1101/2023.02.03.526251","url":null,"abstract":"<p><p>Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder caused by mutations in MECP2. Elevated circulating levels of the adipocyte hormone leptin are consistently observed in patients and in mouse models, yet their contribution to disease progression has remained unclear. Here, we show that reducing leptin signaling, either pharmacologically or genetically, significantly alleviates RTT-like phenotypes in Mecp2-deficient mice. In males, these interventions preserved general health, prevented weight loss, and improved breathing and locomotor functions. At the neuronal level, they restored excitatory/inhibitory balance in the hippocampus and somatosensory cortex and rescued hippocampal synaptic plasticity. In females, delaying the pathological rise of leptin levels postponed symptom progression. These findings uncover leptin as a key contributor to RTT pathophysiology and position leptin-targeted interventions as a promising therapeutic strategy for this currently untreatable disorder.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10685305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional genomic analysis of non-canonical DNA regulatory elements of the aryl hydrocarbon receptor.","authors":"Shayan Shahriar, Tajhal D Patel, Manjula Nakka, Sandra L Grimm, Cristian Coarfa, Daniel A Gorelick","doi":"10.1101/2023.05.01.538985","DOIUrl":"10.1101/2023.05.01.538985","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor activated by environmental toxicants like halogenated and polycyclic aromatic hydrocarbons, which then binds to DNA and regulates gene expression. AHR is implicated in numerous physiological processes, including liver and immune function, cell cycle control, oncogenesis, and metabolism. Traditionally, AHR binds a consensus DNA sequence (GCGTG), the xenobiotic response element (XRE), recruits coregulators, and modulates gene expression. Yet, recent evidence suggests AHR can also regulate gene expression via a non-consensus sequence (GGGA), termed the non-consensus XRE (NC-XRE). The prevalence and functional significance of NC-XRE motifs in the genome have remained unclear. While ChIP and reporter studies hinted at AHR-NC-XRE interactions, direct evidence for transcriptional regulation in a native context was lacking. In this study, we analyzed AHR binding to NC-XRE sequences genome-wide in mouse liver, integrating ChIP-seq and RNA-seq data to identify candidate AHR target genes containing NC-XRE motifs in their regulatory regions. We found NC-XRE motifs in 82% of AHR-bound DNA, significantly enriched compared to random regions, and present in promoters and enhancers of AHR targets. Functional genomics on the Serpine1 gene revealed that deleting NC-XRE motifs reduced TCDD-induced Serpine1 upregulation, demonstrating direct regulation. These findings provide the first direct evidence for AHR-mediated regulation via NC-XRE in a natural genomic context, advancing our understanding of AHR-bound DNA and its impact on gene expression and physiological relevance.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/26/49/nihpp-2023.05.01.538985v1.PMC10187216.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10425783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Sry</i> -modified laboratory rat lines to study sex-chromosome effects underlying sex differences in physiology and disease: Four Core Genotypes and more.","authors":"Arthur P Arnold, Xuqi Chen, Michael N Grzybowski, Janelle M Ryan, Dale R Sengelaub, Tara Mohanroy, V Andree Furlan, Helen R Schmidtke, Jeremy W Prokop, Monika Tutaj, William Grisham, Shanie Landen, Lynn Malloy, Akiko Takizawa, Julia L Ciosek, Kai Li, Theodore S Kalbfleisch, Hayk Barseghyan, Carrie B Wiese, Laurent Vergnes, Karen Reue, Jonathan Wanagat, Helen Skaletsky, David C Page, Vincent R Harley, Melinda R Dwinell, Aron M Geurts","doi":"10.1101/2023.02.09.527738","DOIUrl":"10.1101/2023.02.09.527738","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Previous research on Four Core Genotypes and XY* mice has been instrumental in establishing important effects of sex-chromosome complement that cause sex differences in physiology and disease. We have generated rat models using similar modifications of the testis-determining gene &lt;i&gt;Sry&lt;/i&gt; , to produce XX and XY rats with the same type of gonad, as well as XO, XXY and XYY rats with varying gonads. The models permit discovery of novel sex-chromosome effects (XX vs. XY) that contribute to sex differences in any rat phenotype, and test for effects of different numbers of X or Y chromosomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;XY rats were created with an autosomal transgene of &lt;i&gt;Sry&lt;/i&gt; , producing XX and XY progeny with testes. In other rats, CRISPR-Cas9 technology was used to remove Y chromosome factors that initiate testis differentiation, producing fertile XY gonadal females. Interbreeding of these lines produced rats with interesting combinations of sex chromosomes and gonads: XO, XX, XY, XXY rats with ovaries; and XO, XX, XY, XXY, and XYY rats with testes. These groups can be compared to detect sex differences caused by sex-chromosome complement (XX vs. XY) and/or by gonadal hormones (rats with testes vs. ovaries). Other comparisons detect the effects of X or Y chromosome number (in gonadal females: XO vs. XX, XX vs. XXY, XO vs. XY, XY vs. XXY; in gonadal males: XY vs. XXY, XY vs. XYY; XX vs. XXY, XO vs. XY).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We measured numerous phenotypes to characterize these models, including gonadal histology, breeding performance, anogenital distance, levels of reproductive hormones, body and organ weights, and central nervous system sexual dimorphisms. Serum testosterone levels were comparable in adult XX and XY gonadal males. Phenotypes previously known to be sexually differentiated by the action of gonadal hormones were found to be similar in XX and XY rats with the same type of gonad, suggesting that XX and XY rats with the same type of gonad have comparable levels of gonadal hormones at various stages of development.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The results establish powerful new models to discriminate sex-chromosome and gonadal hormone effects that cause sexual differences in rat physiology and disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Plain english summary: &lt;/strong&gt;The Four Core Genotypes and XY* mouse models have been broadly useful for determining if sex differences in any mouse phenotype are caused by gonadal hormones, or by sex-chromosome complement (XX vs. XY), and if sex-chromosome effects are caused by X- or Y-linked mechanisms. Using gene knockout and transgenic methods, we have produced laboratory rat models that offer similar capabilities. The new rat models allow investigators to test with relative ease, for the first time, if a sex difference in a rat trait is caused by effects of XX vs. XY sex chromosomes, not mediated by effects of gonadal hormones, and to narrow the search for X or Y","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10740174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic ablation of neuronal mitochondrial calcium uptake impedes Alzheimer's disease progression.","authors":"Pooja Jadiya, Elena Berezhnaya, Devin W Kolmetzky, Dhanendra Tomar, Henry M Cohen, Shatakshi Shukla, Manfred Thomas, Salman Khaledi, Joanne F Garbincius, Liam Kennedy, Oniel Salik, Alycia N Hildebrand, John W Elrod","doi":"10.1101/2023.10.11.561889","DOIUrl":"10.1101/2023.10.11.561889","url":null,"abstract":"<p><p>Loss of _m Ca ²⁺ efflux capacity contributes to the pathogenesis and progression of Alzheimer's disease (AD) by promoting mitochondrial Ca ²⁺ ( _m Ca ²⁺ ) overload. Here, we utilized loss-of-function genetic mouse models to causally evaluate the role of _m Ca ²⁺ uptake by conditionally deleting the mitochondrial calcium uniporter channel (mtCU) in a robust mouse model of AD. Loss of neuronal _m Ca ²⁺ uptake reduced Aβ and tau-pathology, synaptic dysfunction, and cognitive decline in 3xTg-AD mice. Knockdown of <i>Mcu</i> in an <i>in vitro</i> model of AD significantly reduced matrix Ca ²⁺ content, redox imbalance, and mitochondrial dysfunction. The preservation of mitochondrial function rescued the AD-dependent decline in autophagic capacity and protected neurons against amyloidosis and cell death. This was corroborated by <i>in vivo</i> data showing improved mitochondrial structure and apposition in AD mice with loss of neuronal <i>Mcu</i> . These results suggest that inhibition of neuronal _m Ca ²⁺ uptake represents a powerful therapeutic target to impede AD progression.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential migration mechanics and immune responses of glioblastoma subtypes.","authors":"Ghaidan A Shamsan, Chao J Liu, Brooke C Braman, Ruyi Li, Susan K Rathe, Aaron L Sarver, Nima Ghaderi, Mariah M McMahon, Rebecca L Klank, Barbara R Tschida, S Joey McFarren, Pamela C Rosato, David Masopust, Jann N Sarkaria, H Brent Clark, Steven S Rosenfeld, David A Largaespada, David J Odde","doi":"10.1101/2022.06.26.497270","DOIUrl":"10.1101/2022.06.26.497270","url":null,"abstract":"<p><p>Glioblastoma remains a deadly cancer driven in part by invasion of tumor cells into the brain. Transcriptomic analyses have identified distinct molecular subtypes, but mechanistic differences that account for clinical differences are not clear. Here, we show that, as predicted by the motor-clutch model of cell migration, mesenchymal glioma cells are more spread, generate larger traction forces, and migrate faster in brain tissue compared to proneural cells. Despite their rapid migration and comparable proliferation rates in vitro, mice with mesenchymal tumors survive longer than those with proneural tumors. This improved survival correlated with an immune response in the mesenchymal tumors, including T cell-mediated. Consistently, inducing mesenchymal tumors in immunodeficient mice resulted in shorter survival supporting a protective immune role in mesenchymal tumors. Thus, mesenchymal tumors have aggressive migration, but are immunologically 'hot' which suppresses net proliferation. These two features counteract each other and may explain the lack of a strong survival difference between subtypes clinically, while also opening up new opportunities for subtype-specific therapies.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87254180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JAX Animal Behavior System (JABS): A genetics informed, end-to-end advanced behavioral phenotyping platform for the laboratory mouse.","authors":"Anshul Choudhary, Brian Q Geuther, Thomas J Sproule, Glen Beane, Vivek Kohar, Jarek Trapszo, Vivek Kumar","doi":"10.1101/2022.01.13.476229","DOIUrl":"10.1101/2022.01.13.476229","url":null,"abstract":"<p><p>Automated detection of complex animal behavior remains a challenge in neuroscience. Developments in computer vision have greatly advanced automated behavior detection and allow high-throughput preclinical and mechanistic studies. An integrated hardware and software solution is necessary to facilitate the adoption of these advances in the field of behavioral neurogenetics, particularly for non-computational laboratories. We have published a series of papers using an open field arena to annotate complex behaviors such as grooming, posture, and gait as well as higher-level constructs such as biological age and pain. Here, we present our, integrated rodent phenotyping platform, JAX Animal Behavior System (JABS), to the community for data acquisition, machine learning-based behavior annotation and classification, classifier sharing, and genetic analysis. The JABS Data Acquisition Module (JABS-DA) enables uniform data collection with its combination of 3D hardware designs and software for real-time monitoring and video data collection. JABS-Active Learning Module (JABS-AL) allows behavior annotation, classifier training, and validation. We introduce a novel graph-based framework (<i>ethograph</i>) that enables efficient boutwise comparison of JABS-AL classifiers. JABS-Analysis and Integration Module (JABS-AI), a web application, facilitates users to deploy and share any classifier that has been trained on JABS, reducing the effort required for behavior annotation. It supports the inference and sharing of the trained JABS classifiers and downstream genetic analyses (heritability and genetic correlation) on three curated datasets spanning 168 mouse strains that we are publicly releasing alongside this study. This enables the use of genetics as a guide to proper behavior classifier selection. This open-source tool is an ecosystem that allows the neuroscience and genetics community for shared advanced behavior analysis and reduces the barrier to entry into this new field.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88277634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crossover designation recruits condensin to reorganize the meiotic chromosome axis.","authors":"Victor A Leon, Tovah E Markowitz, Soogil Hong, Adhithi R Raghavan, Jonna Heldrich, Keun Kim, Andreas Hochwagen","doi":"10.1101/2020.07.16.207068","DOIUrl":"10.1101/2020.07.16.207068","url":null,"abstract":"<p><p>Crossover recombination supports meiotic chromosome inheritance and fertility by establishing chiasmata between homologous chromosomes prior to the first meiotic division. In addition to the physical exchange of DNA mediated by meiotic recombination, chiasma formation also involves restructuring of the underlying chromosome axis, possibly to help with chiasma maturation or to resolve chromosomal interlocks. Here, we identify condensin as an important regulator of axis remodeling in <i>S. cerevisiae</i> . Condensin is recruited near sites of meiotic crossover designation by pro-crossover factors but is largely dispensable for DNA exchange. Instead, condensin helps to create discontinuities in the meiotic chromosome axis by promoting removal of cohesin. In addition, chromosomes of condensin mutants exhibit unusually common parallel chromatin clouds and experience a chromosomal buildup of the conserved axis remodeler Pch2. Consistent with an important role of axis restructuring at crossover sites, the canonical anaphase-bridge phenotype of condensin mutants is partly rescued by redirecting meiotic DNA repair to sister chromatids instead of homologous chromosomes, suggesting that crossover-associated axis reorganization is important for faithful meiotic chromosome segregation.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74923589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ribofootPrinter: A precision python toolbox for analysis of ribosome profiling data.","authors":"Kyra Kerkhofs, Nicholas R Guydosh","doi":"10.1101/2021.07.04.451082","DOIUrl":"10.1101/2021.07.04.451082","url":null,"abstract":"<p><p>Ribosome profiling is a valuable methodology for measuring changes in a cell's translational program. The approach can report how efficiently mRNA coding sequences are translated and pinpoint positions along mRNAs where ribosomes slow down or arrest. It can also reveal when translation takes place outside coding regions, often with important regulatory consequences. While many useful software tools have emerged to facilitate analysis of these data, packages can become complex and challenging to adapt to specialized needs. We therefore introduce ribofootPrinter, a suite of Python tools designed to offer an accessible and modifiable set of code for analysis of data from ribosome profiling and related types of small RNA sequencing experiments. Alignments are made to a simplified transcriptome to keep the code intuitive and multiple normalization options help facilitate interpretation of meta analysis, particularly outside coding regions. We demonstrate how mapping of short reads to the transcriptome increases the frequency of matches to multiple sites and we provide multimapper identifier files to highlight these regions. Overall, this tool has the capability to carry out sophisticated analysis while maintaining enough simplicity to make it readily understandable and adaptable.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87901769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}