bioRxiv : the preprint server for biology最新文献

{"title":"Distinct genetic underpinnings of inter-individual differences in the sensorimotor-association axis of cortical organisation.","authors":"Giacomo Bignardi, Michel G Nivard, H Lina Schaare, Boris C Bernhardt, Richard A I Bethlehem, Simon E Fisher, Sofie L Valk","doi":"10.1101/2023.07.13.548817","DOIUrl":"10.1101/2023.07.13.548817","url":null,"abstract":"<p><p>In humans, many neurobiological features of the cortex-including gene expression patterns, microstructure, and functional connectivity-vary systematically along a sensorimotor-association (S-A) axis of brain organisation. To date, it is still poorly understood whether inter-individual differences in patterns of S-A axis capture these robust spatial relationships across neurobiological properties observed at the group-level. Here, we examine inter-individual differences in structural and functional properties of the S-A axis, namely cortical microstructure, geodesic distances, and the functional gradient, in a sample of young adults from the Human Connectome Project (N = 992, including 328 twins). We quantified heritable variation associated with inter-individual differences in the S-A axis, and assessed whether structural and functional properties that are highly spatially correlated at the group-level also share genetic underpinnings. To consider measurement errors in resting-state functional connectivity data and their impact on properties of the S-A axis, we used a multivariate twin design capable of disentangling individual-level variation in both intra- and inter-individual differences. After accounting for some of the intra-individual variation, we found average heritable individual differences in both the functional gradient <math> <mrow> <mfenced> <mrow> <msup><msub><mi>h</mi> <mrow><mrow><mtext>twin</mtext></mrow> </mrow> </msub> <mn>2</mn></msup> <mo>=</mo> <mn>57</mn> <mtext>%</mtext></mrow> </mfenced> </mrow> </math> , cortical microstructure <math> <mrow> <mfenced> <mrow> <msup><msub><mi>h</mi> <mrow><mrow><mtext>twin</mtext></mrow> </mrow> </msub> <mn>2</mn></msup> <mo>=</mo> <mn>43</mn> <mtext>%</mtext></mrow> </mfenced> </mrow> </math> , and geodesic distances <math> <mrow> <mfenced> <mrow> <msup><msub><mi>h</mi> <mrow><mrow><mtext>twin</mtext></mrow> </mrow> </msub> <mn>2</mn></msup> <mo>=</mo> <mn>34</mn> <mtext>%</mtext></mrow> </mfenced> </mrow> </math> . However, these genetic influences were mostly distinct and deviated from group-level patterns. In particular, we found no significant genetic correlation between the functional gradient and microstructure, while we found both positive and negative genetic associations between the functional gradient and geodesic distances. Our approach highlights the complexity of genetic contributions to brain organisation and may have potential implications for understanding cognitive variability within the S-A axis framework.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84324053","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":"Information-Content-Informed Kendall-tau Correlation Methodology: Interpreting Missing Values as Useful Information.","authors":"Robert M Flight, Praneeth S Bhatt, Hunter Nb Moseley","doi":"10.1101/2022.02.24.481854","DOIUrl":"10.1101/2022.02.24.481854","url":null,"abstract":"<p><strong>Background: </strong>Almost all correlation measures currently available are unable to directly handle missing values. Typically, missing values are either ignored completely by removing them or are imputed and used in the calculation of the correlation coefficient. In either case, the correlation value will be impacted based on a perspective that the missing data represents no useful information. However, missing values occur in real data sets for a variety of reasons. In omics data sets that are derived from analytical measurements, a major reason for missing values is that a specific measurable phenomenon falls below the detection limits of the analytical instrumentation (left-censored values). These missing data are not missing at random, but represent useful information by virtue of their \"missingness\" at one end of the data distribution.</p><p><strong>Results: </strong>To include this information due to left-censorship missingness, we propose the information-content-informed Kendall-tau (ICI-Kt) methodology. We show how left-censored missing values can be included within the definition of the Kendall-tau correlation coefficient, and how that inclusion leads to an interpretation of information being added to the correlation. We also implement calculations for additional measures of theoretical maxima and pairwise completeness that add further layers of information interpretation in the methodology. Using both simulated and real data sets from RNA-seq, metabolomics, and lipidomics experiments, we demonstrate that the ICI-Kt methodology allows for the inclusion of left-censored missing data values as interpretable information, enabling both improved determination of outlier samples and improved feature-feature network construction. We provide explicitly parallel implementations in both R and Python that allow fast calculations of all the variables used when applying the ICI-Kt methodology on large numbers of samples.</p><p><strong>Conclusions: </strong>The ICI-Kt methods are available as an R package and Python module on GitHub at https://github.com/moseleyBioinformaticsLab/ICIKendallTau and https://github.com/moseleyBioinformaticsLab/icikt, respectively.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75088567","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":"Human EEG and artificial neural networks reveal disentangled representations and processing timelines of object real-world size and depth in natural images.","authors":"Zitong Lu, Julie D Golomb","doi":"10.1101/2023.08.19.553999","DOIUrl":"10.1101/2023.08.19.553999","url":null,"abstract":"<p><p>Remarkably, human brains have the ability to accurately perceive and process the real-world size of objects, despite vast differences in distance and perspective. While previous studies have delved into this phenomenon, distinguishing the processing of real-world size from other visual properties, like depth, has been challenging. Using the THINGS EEG2 dataset with human EEG recordings and more ecologically valid naturalistic stimuli, our study combines human EEG and representational similarity analysis to disentangle neural representations of object real-world size from retinal size and perceived depth, leveraging recent datasets and modeling approaches to address challenges not fully resolved in previous work. We report a representational timeline of visual object processing: object real-world depth processed first, then retinal size, and finally, real-world size. Additionally, we input both these naturalistic images and object-only images without natural background into artificial neural networks. Consistent with the human EEG findings, we also successfully disentangled representation of object real-world size from retinal size and real-world depth in all three types of artificial neural networks (visual-only ResNet, visual-language CLIP, and language-only Word2Vec). Moreover, our multi-modal representational comparison framework across human EEG and artificial neural networks reveals real-world size as a stable and higher-level dimension in object space incorporating both visual and semantic information. Our research provides a temporally resolved characterization of how certain key object properties - such as object real-world size, depth, and retinal size - are represented in the brain, which offers further advances and insights into our understanding of object space and the construction of more brain-like visual models.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/56/01/nihpp-2023.08.19.553999v1.PMC10473678.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10165932","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":"Viral expansion after transfer is a primary driver of influenza A virus transmission bottlenecks.","authors":"Katie E Holmes, David VanInsberghe, Lucas M Ferreri, Baptiste Elie, Ketaki Ganti, Chung-Young Lee, Anice C Lowen","doi":"10.1101/2023.11.19.567585","DOIUrl":"10.1101/2023.11.19.567585","url":null,"abstract":"<p><p>For many viruses, narrow bottlenecks acting during transmission sharply reduce genetic diversity in a recipient host relative to the donor. Since genetic diversity represents adaptive potential, such losses of diversity are thought to limit the opportunity for viral populations to undergo antigenic change and other adaptive processes. Thus, a detailed picture of evolutionary dynamics during transmission is critical to understanding the forces driving viral evolution at an epidemiologic scale. To advance this understanding, we used a barcoded virus library and a guinea pig model of transmission to decipher where in the transmission process influenza A virus populations lose diversity. In inoculated guinea pigs, we show that a high level of viral barcode diversity is maintained. Within-host continuity in the barcodes detected across time furthermore indicates that stochastic effects are not pronounced within the inoculated hosts. Importantly, in both aerosol-exposed and direct contact animals, we observed many barcodes at the earliest time point(s) positive for infectious virus, indicating robust transfer of diversity through the environment. This high viral diversity is short-lived, however, with a sharp decline seen 1-2 days after initiation of infection. Although major losses of diversity at transmission are well described for influenza A virus, our data indicate that events that occur following viral transfer and during the earliest stages of natural infection have a central role in this process. This finding suggests that host factors, such as immune effectors, may have greater opportunity to impose selection during influenza A virus transmission than previously recognized.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138447445","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":"Confounding Fuels Misinterpretation in Human Genetics.","authors":"John W Benning, Jedidiah Carlson, Olivia S Smith, Ruth G Shaw, Arbel Harpak","doi":"10.1101/2023.11.01.565061","DOIUrl":"10.1101/2023.11.01.565061","url":null,"abstract":"<p><p>The scientific literature has seen a resurgence of interest in genetic influences on human behavior and socioeconomic outcomes. Such studies face the central difficulty of distinguishing possible causal influences, in particular genetic and non-genetic ones. When confounding between possible influences is not rigorously addressed, it invites over- and misinterpretation of data. We illustrate the breadth of this problem through a discussion of the literature and a reanalysis of two examples. Clark (2023) suggested that patterns of similarity in social status between relatives indicate that social status is largely determined by one's DNA. We show that the paper's conclusions are based on the conflation of genetic and non-genetic transmission (for example, of wealth) within families. Song & Zhang (2024) posited that genetic variants underlying bisexual behavior are maintained in the population because they also affect risk-taking behavior, thereby conferring an evolutionary fitness advantage through increased sexual promiscuity. In this case, too, we show that possible explanations cannot be distinguished, but only one is chosen and presented as a conclusion. We discuss how issues of confounding apply more broadly to studies that claim to establish genetic underpinnings to human behavior and societal outcomes.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10635045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157654","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":"Matrix-associated extracellular vesicles modulate smooth muscle cell adhesion and directionality by presenting collagen VI.","authors":"Alexander Kapustin, Sofia Serena Tsakali, Meredith Whitehead, George Chennell, Meng-Ying Wu, Chris Molenaar, Anton Kutikhin, Yimeng Chen, Sadia Ahmad, Leo Bogdanov, Maxim Sinitsky, Kseniya Rubina, Aled Clayton, Frederik J Verweij, Dirk Michiel Pegtel, Simona Zingaro, Arseniy Lobov, Bozhana Zainullina, Dylan Owen, Maddy Parsons, Richard E Cheney, Derek Warren, Martin James Humphries, Thomas Iskratsch, Mark Holt, Catherine M Shanahan","doi":"10.1101/2023.08.17.551257","DOIUrl":"10.1101/2023.08.17.551257","url":null,"abstract":"<p><p>The extracellular matrix (ECM) supports blood vessel architecture and functionality and undergoes active remodelling during vascular repair and atherogenesis. Vascular smooth muscle cells (VSMCs) are essential for vessel repair and, via their secretome, can invade from the vessel media into the intima to mediate ECM remodelling. Accumulation of fibronectin (FN) is a hallmark of early vascular repair and atherosclerosis. Here we show that FN stimulates VSMCs to secrete small extracellular vesicles (sEVs) by activating the β1 integrin/FAK/Src pathway as well as Arp2/3-dependent branching of the actin cytoskeleton. We found that sEVs are trapped by the ECM in vitro and colocalise with FN in symptomatic atherosclerotic plaques in vivo. Functionally, ECM-trapped sEVs induced the formation of focal adhesions (FA) with enhanced pulling forces at the cellular periphery preventing cellular spreading and adhesion. Proteomic and GO pathway analysis revealed that VSMC-derived sEVs display a cell adhesion signature and are specifically enriched with collagen VI on the sEV surface. In vitro assays identified collagen VI as playing a key role in cell adhesion and invasion directionality. Taken together our data suggests that the accumulation of FN is a key early event in vessel repair acting to promote secretion of collage VI enriched sEVs by VSMCs. These sEVs stimulate directional invasion, most likely by triggering peripheral focal adhesion formation and actomyosin contraction to exert sufficient traction force to enable VSMC movement within the complex vascular ECM network.</p><p><strong>Figure abstract: </strong>Vascular smooth muscle cells sense fibronectin via β1 integrin and secrete small extracellular vesicles loaded with collagen VI. These extracellular vesicles are entrapped in the extracellular matrix and induce formation of peripheral focal adhesions presenting adhesion complex ECM proteins including collagen VI, LGALS3BP, EDIL3 and TGFBI. Focal adhesions anchor the extracellular matrix to actin fibrils in the cell. Contraction of the actin fibrils generates the mechanical force for directional cell invasion through the matrix. This figure was created with BioRender ( https://biorender.com/ ).</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10577190","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":"Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration.","authors":"Silas A Buck, Sophie A Rubin, Tenzin Kunkhyen, Christoph D Treiber, Xiangning Xue, Lief E Fenno, Samuel J Mabry, Varun R Sundar, Zilu Yang, Divia Shah, Kyle D Ketchesin, Darius D Becker-Krail, Iaroslavna Vasylieva, Megan C Smith, Florian J Weisel, Wenjia Wang, M Quincy Erickson-Oberg, Emma I O'Leary, Eshan Aravind, Charu Ramakrishnan, Yoon Seok Kim, Yanying Wu, Matthias Quick, Jonathan A Coleman, William A MacDonald, Rania Elbakri, Abby L Olsen, Emily M Rocha, Gary W Miller, Briana R De Miranda, Michael J Palladino, Brian D McCabe, Kenneth N Fish, Marianne L Seney, Stephen Rayport, Susana Mingote, Karl Deisseroth, Thomas S Hnasko, Rajeshwar Awatramani, Alan M Watson, Scott Waddell, Claire E J Cheetham, Ryan W Logan, Zachary Freyberg","doi":"10.1101/2023.10.02.560584","DOIUrl":"10.1101/2023.10.02.560584","url":null,"abstract":"<p><p>Parkinson's disease (PD) targets some dopamine (DA) neurons more than others. Sex differences offer insights, with females more protected from DA neurodegeneration. The mammalian vesicular glutamate transporter VGLUT2 and <i>Drosophila</i> ortholog dVGLUT have been implicated as modulators of DA neuron resilience. However, the mechanisms by which VGLUT2/dVGLUT protects DA neurons remain unknown. We discovered DA neuron dVGLUT knockdown increased mitochondrial reactive oxygen species in a sexually dimorphic manner in response to depolarization or paraquat-induced stress, males being especially affected. DA neuron dVGLUT also reduced ATP biosynthetic burden during depolarization. RNA sequencing of VGLUT⁺ DA neurons in mice and flies identified candidate genes that we functionally screened to further dissect VGLUT-mediated DA neuron resilience across PD models. We discovered transcription factors modulating dVGLUT-dependent DA neuroprotection and identified dj-1β as a regulator of sex-specific DA neuron dVGLUT expression. Overall, VGLUT protects DA neurons from PD-associated degeneration by maintaining mitochondrial health.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/0e/nihpp-2023.10.02.560584v1.PMC10592912.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694684","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":"Machine Learning-Guided Differentiation Therapy Targets Cancer Stem Cells in Colorectal Cancers.","authors":"Saptarshi Sinha, Joshua Alcantara, Kevin Perry, Vanessa Castillo, Annelies Ondersma, Satarupa Banerjee, Ella McLaren, Celia R Espinoza, Sahar Taheri, Eleadah Vidales, Courtney Tindle, Adel Adel, Siamak Amirfakhri, Joseph R Sawires, Jerry Yang, Michael Bouvet, Pradipta Ghosh","doi":"10.1101/2023.09.13.557628","DOIUrl":"10.1101/2023.09.13.557628","url":null,"abstract":"<p><p>Despite advances in artificial intelligence (AI) within cancer research, its application toward realizing differentiation therapy in solid tumors remains limited. Using colorectal cancer (CRC) as a model, we developed a machine learning (ML) framework, <b><i>CANDiT</i></b> ( <i>Cancer Associated Nodes for Differentiation Targeting</i> ), to selectively induce differentiation and death of cancer stem cells (CSCs)-a key obstacle to durable response. Centering on one node, <i>CDX2</i> , a master differentiation factor lost in high-risk, poorly differentiated CRCs, we built a transcriptomic network to identify therapeutic strategies for CDX2 restoration. Network-based prioritization identified <i>PRKAB1</i> , a stress polarity sensor, as a top target. A clinical-grade PRKAB1 agonist reprogrammed transcriptional networks, induced crypt differentiation, and selectively eliminated CDX2-low CSCs in CRC cell lines, xenografts and patient-derived organoids (PDOs). Multivariate analyses in PDOs revealed a strong therapeutic index, linking efficacy (IC₅₀) to the biomarker-defined CDX2-low state. A 50-gene response signature-derived from an integrated analyses of all three models and trained across multiple datasets-revealed that CDX2 restoration therapy may translate into a ∼50% reduction in recurrence and mortality risk. Mechanistically, treatment activated a differentiation-associated stress polarity signaling axis while dismantling Wnt and YAP-driven stemness programs essential to CSC survival. Thus, <i>CANDiT</i> offers a scalable path to CSC-directed therapy in solid tumors by translating transcriptomic vulnerabilities into precision treatments.</p><p><strong>Graphic abstract: </strong></p><p><strong>One sentence summary: </strong>In this work, Sinha et al. introduce a machine learning-guided framework to identify and target transcriptomic vulnerabilities in colorectal cancer, demonstrating that differentiation therapy selectively eliminates cancer stem cells and reduces recurrence risk.</p><p><strong>Highlights: </strong>An ML framework ( <i>CANDiT</i> ) identifies target for differentiation therapy for CRCs Therapy induces crypt differentiation and CSC-specific cytotoxicityCDX2-low state predicts therapeutic response; restoration improves prognosisTherapy dismantles stemness via reactivation of stress polarity signaling.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10515918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41142402","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":"The systematic assessment of completeness of public metadata accompanying omics studies in the Gene Expression Omnibus.","authors":"Yu-Ning Huang, Pooja Vinod Jaiswal, Anushka Rajesh, Anushka Yadav, Dottie Yu, Fangyun Liu, Grace Scheg, Emma Shih, Grigore Boldirev, Irina Nakashidze, Aditya Sarkar, Jay Himanshu Mehta, Ke Wang, Khooshbu Kantibhai Patel, Mustafa Ali Baig Mirza, Kunali Chetan Hapani, Qiushi Peng, Ram Ayyala, Ruiwei Guo, Shaunak Kapur, Tejasvene Ramesh, Dumitru Ciorbă, Viorel Munteanu, Viorel Bostan, Mihai Dimian, Malak S Abedalthagafi, Serghei Mangul","doi":"10.1101/2021.11.22.469640","DOIUrl":"10.1101/2021.11.22.469640","url":null,"abstract":"<p><p>Recent advances in high-throughput sequencing technologies have made it possible to collect and share a massive amount of omics data, along with its associated metadata. Enhancing metadata availability is critical to ensure data reusability and reproducibility and to facilitate novel biomedical discoveries through effective data reuse. Yet, incomplete metadata accompanying public omics data may hinder reproducibility and reusability by reducing sample interpretability and limiting secondary analyses. In this study, we performed a comprehensive assessment of metadata completeness shared in both scientific publications and/or public repositories by analyzing over 253 studies encompassing over 164 thousands samples, including both human and non-human mammalian studies. We observed that studies often omit over a quarter of important phenotypes, with an average of only 74.8% of them shared either in the text of publication or the corresponding repository. Notably, public repositories alone contained 62% of the metadata, surpassing the textual content of publications by 3.5%. Only 11.5% of studies completely shared all phenotypes, while 37.9% shared less than 40% of the phenotypes. Studies involving non-human samples were more likely to share metadata than studies involving human samples. We observed similar results on the extended dataset spanning 2.1 million samples across over 61,000 studies from the Gene Expression Omnibus repository. The limited availability of metadata reported in our study emphasizes the necessity for improved metadata sharing practices and standardized reporting. Finally, we discuss the numerous benefits of improving the availability and quality of metadata to the scientific community and beyond, supporting data-driven decision-making and policy development in the field of biomedical research. This work provides a scalable framework for evaluating metadata availability and may help guide future policy and infrastructure development.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75449785","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":"The transcription factor CLAMP is required for neurogenesis in <i>Drosophila melanogaster</i>.","authors":"Maria A Tsiarli, James A Kentro, Ashley M Conard, Lucy Xu, Erica Nguyen, Kate O'Connor-Giles, Erica N Larschan","doi":"10.1101/2020.10.09.333831","DOIUrl":"10.1101/2020.10.09.333831","url":null,"abstract":"<p><p>Neural stem cell (NSC) differentiation is controlled by cell-intrinsic and external signals from the stem cell niche including niche surface glia (SG). However, the mechanisms by which transcription factors drive NSC differentiation within the niche remain largely unknown. Here, we show that the <i>Drosophila</i> melanogaster transcription factor, Chromatin-linked adaptor for MSL proteins (CLAMP) is required for regulation of stemness and proliferation of NSCs, especially of the optic lobe (OL). CLAMP promotes transcription of genes involved in stemness, proliferation, and glial development and represses transcription of genes involved in neurogenesis and niche survival. Consistent with transcriptional changes, CLAMP promotes NSC proliferation and niche SG production, while lack of CLAMP severely and specifically impacts OL development. To identify potential mechanisms by which CLAMP may regulate brain development, we examined CLAMP motifs and available CLAMP ChIP-seq data to determine which genes may be direct versus indirect targets. CLAMP motifs are present at many target genes including the glial-determining gene, <i>glial cells missing,</i> while <i>Tailless</i>, the master regulator of OL-development is directly bound by CLAMP. In accordance to these results, in larval OL NSCs lacking CLAMP, Tailless levels are decreased dramatically, suggesting that CLAMP controls OL neurogenesis <i>via</i> Tailless. Overall, our results suggest that CLAMP regulates a transcriptional program which drives NSC proliferation and differentiation <i>via</i> cell-intrinsic and niche-dependent mechanisms that involve transcriptional regulation of <i>Tailless</i> and niche glia.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"120 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87768591","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}