bioRxiv : the preprint server for biology最新文献

{"title":"Selective control of prefrontal neural timescales by parietal cortex.","authors":"Orhan Soyuhos, Tirin Moore, Rishidev Chaudhuri, Xiaomo Chen","doi":"10.1101/2024.09.30.615928","DOIUrl":"10.1101/2024.09.30.615928","url":null,"abstract":"<p><p>Intrinsic neural timescales quantify how long a pattern of spontaneous neuronal activity persists, thereby capturing the dynamics of its endogenous fluctuations over time. We measured the intrinsic timescales of frontal eye field (FEF) neurons and examined their changes during posterior parietal cortex (PPC) inactivation. We observed two distinct classes of FEF neurons, those with short (~25ms) or long (~100ms) timescales. Short-timescale neurons showed stronger transient visual responses, whereas long-timescale neurons exhibited stronger sustained modulation by stimulus-driven attention. During PPC inactivation, intrinsic timescales increased in both neuron types, but occurred predominantly in short-timescale neurons. In addition, PPC inactivation reduced visual and attentional modulation, particularly impairing attentional modulation in long-timescale neurons. Our results provide the first causal evidence of a selective dependence of intrinsic local neural timescales on long-range connections. These findings suggest the presence of at least two network motifs with different timescales that contribute to neuronal dynamics and functional computations in the FEF.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082870","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":"Dual-responsive synthetic gene circuit for dynamic biologic drug delivery via inflammatory and circadian signaling pathways.","authors":"Amanda Cimino, Fiona Pat, Omolabake Oyebamiji, Christine T N Pham, Erik D Herzog, Farshid Guilak","doi":"10.1101/2025.03.20.644403","DOIUrl":"https://doi.org/10.1101/2025.03.20.644403","url":null,"abstract":"<p><strong>Background: </strong>Engineered cells provide versatile tools for precise, tunable drug delivery, especially when synthetic stimulus-responsive gene circuits are incorporated. In many complex disease conditions, endogenous pathologic signals such as inflammation can vary dynamically over different time scales. For example, in autoimmune conditions such as rheumatoid arthritis or juvenile idiopathic arthritis, local (joint) and systemic inflammatory signals fluctuate daily, peaking in the early morning, but can also persist over long periods of time, triggering flare-ups that can last weeks to months. However, treatment with disease-modifying anti-rheumatic drugs is typically provided at continuous high doses, regardless of disease activity and without consideration for levels of inflammatory signals. In previous studies, we have developed cell-based drug delivery systems that can automatically address the different scales of flares using either chronogenetic circuits (i.e., clock gene-responsive elements) that can be tuned for optimal drug delivery to dampen circadian variations in inflammatory levels or inflammation-responsive circuits (i.e., NF-κB-sensitive elements) that can respond to sustained arthritis flares on demand with proportional synthesis of drug. The goal of this study was to develop a novel dual-responsive synthetic gene circuit that responds to both circadian and inflammatory inputs using OR-gate logic for both daily timed therapeutic output and enhanced therapeutic output during chronic inflammatory conditions.</p><p><strong>Results: </strong>We developed a synthetic gene circuit driven by tandem inflammatory NF-κB and circadian E'-box response elements. When engineered into induced pluripotent stem cells that were chondrogenically differentiated, the gene circuit demonstrated basal-level circadian output with enhanced stimulus-responsive output during an inflammatory challenge shown by bioluminescence monitoring. Similarly, this system exhibited enhanced therapeutic levels of biologic drug interleukin-1 receptor antagonist (IL-1Ra) during an inflammatory challenge in differentiated cartilage pellets. This dual-responsive therapeutic gene circuit mitigated both the inflammatory response as measured by bioluminescence reporter output and tissue-level degradation during conditions mimicking an arthritic flare.</p><p><strong>Conclusions: </strong>The dual-responsive synthetic gene circuit developed herein responds to input cues from two key homeostatic transcriptional networks, enabling dynamic and tunable output. This proof-of-concept approach has the potential to match drug delivery to disease activity for optimal outcomes that addresses the complex environment of inflammatory arthritis.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757318","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":"Transcriptional responses to chronic oxidative stress require cholinergic activation of G-protein-coupled receptor signaling.","authors":"Kasturi Biswas, Caroline Moore, Hannah Rogers, Khursheed A Wani, Read Pukkila-Worley, Daniel P Higgins, Amy K Walker, Gregory P Mullen, James B Rand, Michael M Francis","doi":"10.1101/2025.01.06.628021","DOIUrl":"10.1101/2025.01.06.628021","url":null,"abstract":"<p><p>Organisms have evolved protective strategies that are geared toward limiting cellular damage and enhancing organismal survival in the face of environmental stresses, but how these protective mechanisms are coordinated remains unclear. Here, we define a requirement for neural activity in mobilizing the antioxidant defenses of the nematode <i>Caenorhabditis elegans</i> both during chronic oxidative stress and prior to its onset. We show that acetylcholine-deficient mutants are particularly vulnerable to chronic oxidative stress. We find that extended oxidative stress mobilizes a broad transcriptional response which is strongly dependent on both cholinergic signaling and activation of the muscarinic G-protein acetylcholine coupled receptor (mAChR) GAR-3. Gene enrichment analysis revealed a lack of upregulation of proteasomal proteolysis machinery in both cholinergic-deficient and <i>gar-3</i> mAChR mutants, suggesting that muscarinic activation is critical for stress-responsive upregulation of protein degradation pathways. Further, we find that GAR-3 overexpression in cholinergic motor neurons prolongs survival during chronic oxidative stress. Our studies demonstrate neuronal modulation of antioxidant defenses through cholinergic activation of G protein-coupled receptor signaling pathways, defining new potential links between cholinergic signaling, oxidative damage, and neurodegenerative disease.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019863","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":"Predator odor stress produces sex- and subpopulation-specific increases in alcohol drinking, anxiety-like behavior, and lateral hypothalamic <i>crh</i> expression.","authors":"S M Bonauto, O R Brunke, F M Vassoler, M M Weera","doi":"10.1101/2025.03.20.644324","DOIUrl":"https://doi.org/10.1101/2025.03.20.644324","url":null,"abstract":"<p><p>Traumatic stress leads to maladaptive avoidance behaviors and alcohol misuse in some people. In rats, predator odor (\"traumatic\") stress produces persistent avoidance of stress-paired contexts and escalated alcohol self-administration in some animals (Avoiders), but not others (Non-Avoiders). This mirrors the individual differences in stress responsivity and alcohol misuse seen in humans. Here, we used a quinine-adulterated alcohol drinking procedure to model compulsive-like alcohol drinking in humans. Male and female Wistar rats were given 12 weeks of intermittent access to 20% (v/v) alcohol, followed by three weeks of limited access. Rats were then indexed for avoidance using predator odor stress exposure, and limited access drinking resumed for three additional weeks after stress. During this period, the alcohol solution was adulterated twice weekly with increasing concentrations of quinine. More Avoidant males were more resistant to quinine adulteration and Avoider males increased in non-quinine alcohol drinking. Using ultrasonic vocalizations (USVs) as a measure of affective state, we found that Non-Avoider males emitted more lower frequency USVs (<32 kHz) preceding, during, and following predator odor stress. Finally, quantification of <i>crh, crhr1, crhr2, crhbp</i> gene expression in the lateral hypothalamus revealed a strong positive correlation between greater <i>crh</i> transcripts and avoidance in males and a positive correlation between <i>crh</i> transcripts and less anxiety-like behaviors in females. Together, these results suggest that the intersection of stress and compulsive-like alcohol drinking is sex-specific and dependent on individual differences in stress outcomes. This work reinforces the importance of considering sex differences in stress and alcohol use disorder research.</p><p><strong>Highlights: </strong>Male Avoider rats show elevated two-bottle choice alcohol drinking after predator odor stressMore avoidant males show more aversion-resistant alcohol drinkingFemale Avoider rats show heightened anxiety-like behavior 4 weeks after stressLow frequency USVs predict Non-Avoider behavior in male rats <i>Crh</i> expression in the LH is correlated with avoidance and alcohol drinking in male rats.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756654","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":"Rapid fluctuations in histamine associated with intake of nutritive and non-nutritive solutions.","authors":"K L Volcko, A Gresch, B Benowitz, H Taghipourbibalan, M Visser, G D Stuber, A G Gordon-Fennell, T Patriarchi, J E McCutcheon","doi":"10.1101/2024.11.07.622425","DOIUrl":"10.1101/2024.11.07.622425","url":null,"abstract":"<p><p>The neurotransmitter histamine is involved in control of food intake, yet its dynamics during individual feeding episodes remain unexplored. Therefore, we used the novel genetically-encoded histamine sensor, HisLightG, combined with fiber photometry to measure histamine release in two hypothalamic regions critical for the food-suppressive effects of histamine, the paraventricular nucleus of the hypothalamus (PVH), and the ventromedial hypothalamus (VMH). Male mice were tested under different conditions to assess whether hunger, time of day, or the caloric content of the solution they were given affected histamine fluctuations. We found that histamine levels changed rapidly in response to eating. These histamine fluctuations were influenced by experimental conditions, with slightly smaller responses when the test solution was sucralose (both regions) or during the light cycle (PVH only). Notable regional differences were identified, such that in the PVH histamine rebounded to baseline levels, whereas in the VMH histamine remained lower than baseline for at least 10 seconds after licking ceased. In a separate cohort of male and female mice, enhancing histamine tone via administration of a histamine precursor (L-histidine) reduced the number of licks across multiple sucrose concentrations. Together, these findings indicate that histaminergic activity is modulated rapidly during ingestive episodes, and that understanding these release patterns will give insight into histamine's role in appetite suppression.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653243","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":"p62 sorts Lupus La and selected microRNAs into breast cancer-derived exosomes.","authors":"Jordan Matthew Ngo, Justin Krish Williams, Morayma Mercedes Temoche-Diaz, Abinayaa Murugupandiyan, Randy Schekman","doi":"10.1101/2025.03.20.644464","DOIUrl":"https://doi.org/10.1101/2025.03.20.644464","url":null,"abstract":"<p><p>Exosomes are multivesicular body-derived extracellular vesicles that are secreted by metazoan cells. Exosomes have utility as disease biomarkers, and exosome-mediated miRNA secretion has been proposed to facilitate tumor growth and metastasis. Previously, we demonstrated that the Lupus La protein (La) mediates the selective incorporation of miR-122 into metastatic breast cancer-derived exosomes; however, the mechanism by which La itself is sorted into exosomes remains unknown. Using unbiased proximity labeling proteomics, biochemical fractionation, superresolution microscopy and genetic tools, we establish that the selective autophagy receptor p62 sorts La and miR-122 into exosomes. We then performed small RNA sequencing and found that p62 depletion reduces the exosomal secretion of tumor suppressor miRNAs and results in their accumulation within cells. Our data indicate that p62 is a quality control factor that modulates the miRNA composition of exosomes. Cancer cells may exploit p62-dependent exosome cargo sorting to eliminate tumor suppressor miRNAs and thus to promote cell proliferation.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757445","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":"Pyrimidine sufficiency is required for Sae two-component system signaling in <i>Staphylococcus aureus</i>.","authors":"Dennis A DiMaggio, Won-Sik Yeo, Shaun R Brinsmade","doi":"10.1101/2025.03.20.644390","DOIUrl":"https://doi.org/10.1101/2025.03.20.644390","url":null,"abstract":"<p><p>Nucleotide metabolism in pathogens is essential for their virulence, supporting growth, survival, and immune evasion during infection. Virulence in <i>Staphylococcus aureus</i> is driven by the production of virulence factors that facilitate nutrient acquisition and promote immune evasion and subversion. One key virulence regulatory system is the Sae two-component system (TCS), which upregulates the production of various virulence factors. The sensor histidine kinase SaeS, a member of the intramembrane family of histidine kinases (IM-HKs), lacks a signal-binding domain, leaving the mechanisms by which these HKs sense signals and regulate gene expression unclear. We report that de novo pyrimidine biosynthesis is essential for maintaining Sae activity. Disruption of genes involved in pyrimidine biosynthesis reduces Sae-dependent promoter activity under pyrimidine-limited conditions. Phos-tag electrophoresis confirmed that pyrimidine limitation impacts SaeS kinase activity. The effect of pyrimidine limitation on SaeS was abrogated in a strain producing only the catalytic domain, suggesting that pyrimidines regulate SaeS activity at the membrane. Additionally, defective pyrimidine biosynthesis caused membrane defects and increased incorporation of free fatty acids into the membrane. Further, providing an extracellular sink for free fatty acids restored Sae activity in these mutants. Our study highlights the interplay between nucleotide metabolism and membrane integrity in regulating virulence factor expression through signal transduction systems in pathogens.</p><p><strong>Importance: </strong>Virulence is often correlated with nutrient depletion, but our understanding of this coordination is incomplete. In <i>S. aureus</i> , the Sae two-component system (Sae TCS) is a major regulator of virulence factor production and secretion, but as the sensor histidine kinase SaeS lacks an obvious domain to perceive its inducing signal, basic questions surrounding how the kinase is triggered persist. This study aims to investigate the mechanism by which pyrimidines act to promote the activity of the SaeS kinase in <i>S. aureus</i> and further expands on the importance of the roles of pyrimidines in regulating envelope biogenesis. Understanding this intersection between nucleotide metabolism and virulence regulation opens up the possibility for the development of targeted anti-virulence strategies against <i>S. aureus</i> infections.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757574","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":"Structure of a new capsid form and comparison with A-, B- and C-capsids clarify herpesvirus assembly.","authors":"Alexander Stevens, Saarang Kashyap, Ethan Crofut, Ana Lucia Alverez-Cabrera, Jonathan Jih, Yun-Tao Liu, Z Hong Zhou","doi":"10.1101/2025.03.19.644230","DOIUrl":"https://doi.org/10.1101/2025.03.19.644230","url":null,"abstract":"<p><p>Three capsid types have been recognized from the nuclei of herpesvirus-infected cells: empty A-capsids, scaffolding-containing B-capsids, and DNA-filled C-capsids. Despite progress in determining atomic structures of these capsids and extracellular virions in recent years, debate persists concerning the origins and temporal relationships among these capsids during capsid assembly and genome packaging. Here, we have imaged over 300,000 capsids of herpes simplex virus type 1 by cryogenic electron microscopy (cryoEM) and exhaustively classified them to characterize the structural heterogeneity of the DNA-translocating portal complex and their functional states. The resultant atomic structures reveal not only the expected A-, B-, and C-capsids, but also capsids with portal vertices similar to C-capsids but no resolvable genome in the capsid lumen, which we named D-capsids. The dodecameric dsDNA-translocating portal complex varies across these capsid types in their radial positions in icosahedral capsids and exhibits structural dynamics within each capsid type. In D-capsids, terminal DNA density exists in multiple conformations including one reminiscent to that in C-capsids, suggesting D-capsids are products of failed DNA retention. This interpretation is supported by varying amounts of DNA outside individual D-capsids and by correlation of capsid counts observed in situ of infected cell nuclei and those after purification. Additionally, an \"anchoring\" segment of the scaffold protein is resolved interacting with the portal baskets of A- and B-capsids but not D- and C-capsids. Taken together, our data indicate that A-capsids arise from failed DNA packaging and D-capsids from failed genome retention, clarifying the origins of empty capsids in herpesvirus assembly.</p><p><strong>Significance: </strong>As the prototypical herpesvirus, herpes simplex virus 1 (HSV-1) exhibits a global seroprevalence of 67% and approaching 90% in some localities. Herpesvirus infections can cause devastating cancers and birth defects, with HSV-1 infections leading to cold sores among the general population worldwide and blindness in developing nations. Here, we present atomic structures of the capsids sorted out from the nuclear isolates of HSV-1 infected cells, including the previously recognized A-, B-, and C-capsids, as well as the newly identified D-capsid. The structures show the details of protein-protein and protein-DNA interactions within each capsid type and the positional and interactional variability of the viral DNA-translocating portal vertex among these capsids. Importantly, our findings suggest that A-capsids are products of failed dsDNA packaging and D-capsids of failed genome retention. Together, the high-resolution 3D structures clarify the processes of genome packaging, maintenance, and ejection during capsid assembly, which are conserved across all herpesviruses.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757527","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":"BASELINE: A CRISPR Base Editing Platform for Mammalian-Scale Single-Cell Lineage Tracing.","authors":"Evan Winter, Francesco Emiliani, Aidan Cook, Asma Abderrahim, Aaron McKenna","doi":"10.1101/2025.03.19.644238","DOIUrl":"https://doi.org/10.1101/2025.03.19.644238","url":null,"abstract":"<p><p>A cell's fate is shaped by its inherited state, or lineage, and the ever-shifting context of its environment. CRISPR-based recording technologies are a promising solution to map the lineage of a developing system, yet challenges remain regarding single-cell recovery, engineering complexity, and scale. Here, we introduce BASELINE, which uses base editing to generate high-resolution lineage trees in conjunction with single-cell profiling. BASELINE uses the Cas12a adenine base editor to irreversibly edit nucleotides within 50 synthetic target sites, which are integrated multiple times into a cell's genome. We show that BASELINE accumulates lineage-specific marks over a wide range of biologically relevant intervals, recording more than 4300 bits of information in a model of pancreatic cancer, a 50X increase over existing technologies. Single-cell sequencing reveals high-fidelity capture of these recorders, recovering lineage reconstructions up to 40 cell divisions deep, within the estimated range of mammalian development. We expect BASELINE to apply to a wide range of lineage-tracing projects in development and disease, especially in which cellular engineering makes small, more distributed systems challenging.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757225","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 small genomics lab experience optimizing data cold storage.","authors":"Elisha D O Roberson","doi":"10.1101/2025.03.18.643355","DOIUrl":"https://doi.org/10.1101/2025.03.18.643355","url":null,"abstract":"<p><p>Translational research is often a collaborative enterprise that involves basic science researchers, clinicians, and experts in genomics and bioinformatics. While there are central university and industry cores to support data generation, long-term storage often falls to the individual investigators. We frequently fulfill the role of long-term FASTQ file storage for our collaborators. To reduce our cold storage space, we tested the space savings for gzip and zstandard algorithms on an old set of FASTQ files. We found that zstandard had a better overall compression ratio than the best gzip algorithm, amounting to more than 20% space savings overall compared to gzip. It may be worth transitioning to zstandard compression for small, collaborative genomics labs to minimize cold storage costs.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757619","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}