bluuebunny/crossref_metadata_2025_split huggingface dataset:
Giraffe: a tool for comprehensive processing and visualization of multiple long-read sequencing data
Authors: Liu Xudong , Shao Yanwen , Guo Zhihao , Ni Ying , Sun Xuan , Leung Anskar Yu Hung , Li Runsheng 
Published: May 2024

AbstractThird-generation sequencing techniques have become increasingly popular due to their ability to generate long, high-quality reads. Utilizing datasets from various samples and multiple sequencing platforms for comparative and comprehensive analysis is essential for exploring biological mechanisms and establishing benchmark baselines. However, current tools for long reads primarily focus on quality control (QC) and read processing for individual samples, complicating the profiling and comparison of multiple datasets. The lack of tools for data comparison and visualization presents challenges for researchers with limited bioinformatics experience. Furthermore, developing a comprehensive long-read QC method that facilitates comparative analysis and visualization across multiple samples and platforms is necessary to establish benchmark baselines for selecting appropriate sequencing platforms. We introduce Giraffe, a Python3-based command line tool designed for comparative analysis and visualization across multiple samples and platforms. Giraffe enables the assessment of read quality, sequencing bias, and genomic regional methylation proportions for both DNA and direct RNA sequencing reads. Its usability has been demonstrated in various scenarios, including comparisons of different biological processing methods (whole genome amplification vs. shotgun), sequencing platforms (Oxford Nanopore Technology vs. Pacific Biosciences), tissues (kidney marrow with and without blood), and biological replicates (kidney marrows). Additionally, our findings indicate that Oxford Nanopore duplex reads outperform PacBio HiFi reads in homopolymer identification and GC evenness while maintaining comparable overall read quality.
Keys to the cabinet: unlocking biodiversity data in public entomology collections
Authors: Gibson Joel F. , Howse Mackenzie , Paillard Claire , Penfold Cassandra , Penno Alannah , van der Voort Genevieve E. , Huber Dezene P.W. 
Published: May 2024

AbstractCanadian entomology collections contain valuable biodiversity and ecological data, but they must be digitized in order to be usable by those working outside of the collections. Multiple analyses of the digital database of the Odonata collection at the Royal British Columbia Museum were conducted. These analyses reveal that complete digital datasets can be used to explore questions of historical and current geographical distribution and species composition differences based on ecoprovince and elevation. The results of these analyses can be used directly in conservation and climate change impact mitigation decisions. These analyses are only possible because the Odonata collection has received concerted effort to digitize all specimen records. The full value of long-term historical insect biodiversity data can only be accessed once collections are digitized. Additional training and employment of collection management and curatorial staff is essential to optimize the use of abundant, but underutilized, Canadian biodiversity data.
Elucidating immune-related gene transcriptional programs via factorization of large-scale RNA-profiles
Authors: He Shan , Gubin Matthew M. , Rafei Hind , Basar Rafet , Dede Merve , Jiang Xianli , Liang Qingnan , Tan Yukun , Kim Kunhee , Gillison Maura L. , Rezvani Katayoun , Peng Weiyi , Haymaker Cara , Hernandez Sharia , Solis Luisa M. , Mohanty Vakul , Chen Ken 
Published: May 2024

SummaryRecent developments in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy, have encountered challenges such as immune-related adverse events and resistance, especially in solid tumors. To advance the field, a deeper understanding of the molecular mechanisms behind treatment responses and resistance is essential. However, the lack of functionally characterized immune-related gene sets has limited data-driven immunological research. To address this gap, we adopted non-negative matrix factorization on 83 human bulk RNA-seq datasets and constructed 28 immune-specific gene sets. After rigorous immunologist-led manual annotations and orthogonal validations across immunological contexts and functional omics data, we demonstrated that these gene sets can be applied to refine pan-cancer immune subtypes, improve ICB response prediction and functionally annotate spatial transcriptomic data. These functional gene sets, informing diverse immune states, will advance our understanding of immunology and cancer research.
Varroa mites escape the evolutionary trap of haplodiploidy
Authors: Eliash Nurit , Tetsuya Endo , Johnston Spencer J. , Techer Maeva A. , Holmes Valerie R. , Rangel Juliana , Economo Evan P. , Mikheyev Alexander S. 
Published: May 2024

AbstractGenetic diversity is essential for populations adapting to environmental changes. Due to genetic bottlenecks invasive species have reduced genetic diversity. However, they must quickly adapt to changes in new environments, potentially including anthropogenic countermeasures. This paradox raises a fundamental question: how do species adapt to changes while having low genetic diversity? The invasion paradox is more pronounced for some species. Parasites go through additional bottlenecks between hosts. Haplodiploid species have a lower effective population size as males can inherit and transmit only half of their mother’s genome. Trying to solve this paradox, we investigated inheritance in the Varroa mite (Varroa destructor), a well-studied invasive parasite of honey bees fitting all of the above criteria. By following the flow of alleles across three-generation pedigrees we found that Varroa, so far believed to be haplodiploid, is actually not. Rather, it has a unique reproductive system in which females clonally produce functionally diploid sons. While males lose somatic DNA during development, they can transmit either copy of the maternal genome to their daughters. This enhances female fitness, particularly under sib-mating typical of Varroa. We suggest this allows a greater effective population size relative to haplodiploidy and, thus, an increased evolutionary potential. This reversion to diploidy is a singular example of escaping the ‘evolutionary trap’ of haplodiploidy, which is believed to be an evolutionary stable end state. Plasticity in reproductive systems could be more common than assumed, and may potentially explain the remarkable resilience and high adaptivity of Varroa and other invasive parasites.SignificanceVarroa mites have driven the collapse of honey bee populations since their worldwide spread in the middle of the 20th century. Despite repeated genetic bottlenecks, Varroa has adapted to diverse environments and has overcome many pesticides. Using pedigree analysis, we found that Varroa re-evolved diplodiploid reproduction from an evolutionary history of haplodiploidy. Diplodiploidy permits a higher effective population size and evolutionary potential, likely facilitating Varroa’s ongoing success. Females produce males clonally, passing on their entire genomes. Varroa is a singular exception to the theoretically and empirically observed rule that, one evolved, haplodiploidy is an evolutionarily stable end state (an ‘evolutionary trap’). Novel mechanistic studies of even well-known organisms can lead to surprising insights into the evolutionary plasticity of reproductive systems.
BIMSA: Accelerating Long Sequence Alignment Using Processing-In-Memory
Authors: Alonso-Marín Alejandro , Fernandez Ivan , Aguado-Puig Quim , Gómez-Luna Juan , Marco-Sola Santiago , Mutlu Onur , Moreto Miquel 
Published: May 2024

AbstractMotivationRecent advances in sequencing technologies have stressed the critical role of sequence analysis algorithms and tools in genomics and healthcare research. In particular, sequence alignment is a fundamental building block in many sequence analysis pipelines and is frequently a performance bottleneck both in terms of execution time and memory usage. Classical sequence alignment algorithms are based on dynamic programming and often require quadratic time and memory with respect to the sequence length. As a result, classical sequence alignment algorithms fail to scale with increasing sequence lengths and quickly become memory-bound due to data-movement penalties.ResultsProcessing-In-Memory (PIM) is an emerging architectural paradigm that seeks to accelerate memory-bound algorithms by bringing computation closer to the data to mitigate data-movement penalties. This work presents BIMSA (Bidirectional In-MemorySequenceAlignment), a PIM design and implementation for the state-of-the-art sequence alignment algorithm BiWFA (Bidirectional Wavefront Alignment), incorporating new hardware-aware optimizations for a production-ready PIM architecture (UPMEM). BIMSA supports aligning sequences up to 100K bases, exceeding the limitations of state-of-the-art PIM implementations. First, BIMSA achieves speedups up to 22.24×(11.95×on average) compared to state-of-the-art PIM-enabled implementations of sequence alignment algorithms. Second, achieves speedups up to 5.84×(2.83×on average) compared to the highest-performance multicore CPU implementation of BiWFA. Third, BIMSA exhibits linear scalability with the number of compute units in memory, enabling further performance improvements with upcoming PIM architectures equipped with more compute units and achieving speedups up to 9.56×(4.7×on average).AvailabilityCode and documentation are publicly available athttps://github.com/AlejandroAMarin/BIMSA.Contactalejandro.alonso1@bsc.es
WITHDRAWN: Elucidating the molecular mechanism of phytochemicals against Parkinson’s disease through an integrated systems biology and molecular modeling approach
Authors: Bhowmik Ratul , Kumar Sunil , Manaithiya Ajay , Mohan C. Gopi , Mathew Bijo , Parkkila Seppo , Aspatwar Ashok 
Published: May 2024

Withdrawal StatementThe authors have withdrawn their manuscript owing to the inability to complete the revisions or follow up on the manuscript at this time, due to personal circumstances. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
A novel expectation-maximization approach to infer general diploid selection from time-series genetic data
Authors: Fine Adam G. , Steinrücken Matthias 
Published: May 2024

AbstractDetecting and quantifying the strength of selection is a main objective in population genetics. Since selection acts over multiple generations, many approaches have been developed to detect and quantify selection using genetic data sampled at multiple points in time. Such time series genetic data is commonly analyzed using Hidden Markov Models, but in most cases, under the assumption of additive selection. However, many examples of genetic variation exhibiting non-additive mechanisms exist, making it critical to develop methods that can characterize selection in more general scenarios. Thus, we extend a previously introduced expectation-maximization algorithm for the inference of additive selection coefficients to the case of general diploid selection, in which the heterozygote and homozygote fitness are parameterized independently. We furthermore introduce a framework to identify bespoke modes of diploid selection from given data, as well as a procedure for aggregating data across linked loci to increase power and robustness. Using extensive simulation studies, we find that our method accurately and efficiently estimates selection coefficients for different modes of diploid selection across a wide range of scenarios; however, power to classify the mode of selection is low unless selection is very strong. We apply our method to ancient DNA samples from Great Britain in the last 4,450 years, and detect evidence for selection in six genomic regions, including the well-characterized LCT locus. Our work is the first genome-wide scan characterizing signals of general diploid selection.Author SummaryNatural selection increases the likelihood that beneficial genetic variants are passed from parent to offspring and thus forms the basis of genetic adaptation to novel environments. Genomic data sampled at multiple timepoints, such as genetic material extracted from ancient remains (ancient DNA) or data from evolve and resequence experiments, can enable more precise identification of genetic variants subject to selective pressure than contemporary samples alone. However, most methods for identifying genetic variation under selection focus on additive selection, where the fitness of the heterozygote is exactly intermediate between the homozygotes. Leveraging genetic data at multiple timepoints, we develop a method to detect additive and non-additive selection as well as to infer the most likely dominance mechanism. We apply our methods to a dataset of ancient DNA from Great Britain dated less than 4,450 years before present and identify six regions with signals of recent selection, including one at the TFR2 locus that has not been previously reported as a target of selection. Our work enables more accurate quantification of non-additive selection dynamics and can be used to test more complex models of selection.
Screening the human miRNA interactome reveals coordinated upregulation in melanoma, adding bidirectional regulation to miRNA networks
Authors: Jame-Chenarboo Faezeh , Reyes Joseph N. , Twells Nicholas M. , Ng Hoi-Hei , Macdonald Dawn , Hernando Eva , Mahal Lara K. 
Published: May 2024

AbstractCellular protein expression is coordinated post-transcriptionally by an intricate regulatory network. The current presumption is that miRNA work by repression of functionally related targets within a system. In recent work, upregulation of protein expression via direct interactions of mRNA with miRNA has been found in dividing cells, providing an additional mechanism of regulation. Herein, we demonstrate coordinated upregulation of functionally-coupled proteins by miRNA. We focused on CD98hc, the heavy chain of the amino acid transporter LAT1, and α-2,3-sialyltransferases ST3GAL1 and ST3GAL2, which are critical for CD98hc stability in melanoma. Profiling miRNA regulation using our high-throughput miRFluR assay, we identified miRNA that upregulated expression of both CD98hc and either ST3GAL1 or ST3GAL2. These co-upregulating miRNAs were enriched in melanoma datasets associated with transformation and progression. Our findings add co-upregulation by miRNA into miRNA regulatory networks and adds a new bidirectional twist to the impact miRNA have on protein regulation and glycosylation.
Green microwave-assisted extraction ofEuphorbia guyoniana:Optimization, metabolite profile andin vivoanti-inflammatory potential
Authors: Issaadi Halima Meriem , Bachir Yacine Nait , Naama Alaaeddine Ben , Aiter Imad , Szőri Kornél , Hunyadi Attila 
Published: May 2024

AbstractThis study aimed to optimize microwave-assisted extraction of phenolic compounds from undervalued traditional plantEuphorbia guyoniana(Boiss. & Reut.) using central composite design of response surface methodology. The independent variables were extraction time (x1: 5 – 25 min), ethanol concentration in the extractive solvent (x2: 30 – 70%), microwave power (x3: 180 – 800 Watt) and feed-to-solvent ratio (x4: 1:7.5 – 1:17.5) while dependent variables were total phenolic content (TPC) and total flavonoid content (TFC). Extract obtained by using the optimal extraction parameters was evaluated for itsin vivoanti-inflammatory activity by the carrageenan-induced paw edema model and was subjected to RP-HPLC-PDA-ESI-MS analysis to investigate the presence of phenolic compounds. The optimal conditions for highest TPC (377.22 ± 5.42 mg GAE/100g) and TFC (184.40 ± 1.18 mg QE/100g) were obtained at extraction time of 25 min, ethanol concentration of 40.57%, microwave power of 450 Watt and feed-to-solvent ratio of 1:17.5. The quadratic models significantly (p < 0.0001) fitted the experimental data with R2values of 0.984 and 0.970 for TPC and TFC, respectively. Optimal extract ofEuphorbia guyonianasignificantly higher inhibited carrageenan induced inflammation with a concentration of 50 mg/kg (75,98%) when compared with reference anti-inflammatory drug ibuprofen (43,77%). Finally, above the previously reported phenolic constituents, i.e, quercetin and kaempferol derivatives, hydroxycinnamates have been identified for the first time inEuphorbia guyonianaplant extract.
Exploring variations in the implementation of a health system level policy intervention to improve maternal and child health outcomes in resource limited settings: A qualitative multiple case study from Uganda
Authors: Walugembe David Roger , Plamondon Katrina , Kaharuza Frank , Waiswa Peter , Wylie Lloy , Wathen Nadine , Kothari Anita 
Published: May 2024

AbstractBackgroundDespite growing literature, few studies have explored the implementation of policy interventions to reduce maternal and perinatal mortality in low- and middle-income countries (LMICs). Even fewer studies explicitly articulate the theoretical approaches used to understand contextual influences on policy implementation. This under-use of theory may account for the limited understanding of the variations in implementation processes and outcomes. We share findings from a study exploring how a health system-level policy intervention was implemented to improve maternal and child health outcomes in a resource limited LMIC.MethodsOur qualitative multiple case study was informed by the Normalization Process Theory (NPT). It was conducted across eight districts and among ten health facilities in Uganda, with 48 purposively selected participants. These included health care workers located at each of the case sites, policy makers from the Ministry of Health, and from agencies and professional associations. Data were collected using semi-structured, in-depth interviews to understand uptake and use of Uganda’s maternal and perinatal death surveillance and response (MPDSR) policy and were inductively and deductively analyzed using NPT constructs and subconstructs.ResultsWe identified six broad themes that may explain the observed variations in the implementation of the MPDSR policy. These include: 1) perception of the implementation of the policy, 2) leadership of the implementation process, 3) structural arrangements and coordination, 4) extent of management support and adequacy of resources, 5) variations in appraisal and reconfiguration efforts and 6) variations in barriers to implementation of the policy.Conclusion and recommendationsThe variations in sense making and relational efforts, especially perceptions of the implementation process and leadership capacity, had ripple effects across operational and appraisal efforts. Adopting theoretically informed approaches to assessing the implementation of policy interventions is crucial, especially within resource limited settings.
The retrotransposon-derived capsid genesPNMA1andPNMA4maintain reproductive capacity
Authors: Wood Thomas W.P. , Henriques William S. , Cullen Harrison B. , Romero Mayra , Blengini Cecilia S. , Sarathy Shreya , Sorkin Julia , Bekele Hilina , Jin Chen , Kim Seungsoo , Chemiakine Alexei , Khondker Rishad C. , Isola José V.V. , Stout Michael B. , Gennarino Vincenzo A. , Mogessie Binyam , Jain Devanshi , Schindler Karen , Suh Yousin , Wiedenheft Blake , Berchowitz Luke E. 
Published: May 2024

ABSTRACTThe human genome contains 24gag-like capsid genes derived from deactivated retrotransposons conserved among eutherians. Although some of their encoded proteins retain the ability to form capsids and even transfer cargo, their fitness benefit has remained elusive. Here we show that thegag-like genesPNMA1andPNMA4support reproductive capacity. Six-week-old mice lacking eitherPnma1orPnma4are indistinguishable from wild-type littermates, but by six months the mutant mice become prematurely subfertile, with precipitous drops in sex hormone levels, gonadal atrophy, and abdominal obesity; overall they produce markedly fewer offspring than controls. Analysis of donated human ovaries shows that expression of both genes declines normally with aging, while severalPNMA1andPNMA4variants identified in genome-wide association studies are causally associated with low testosterone, altered puberty onset, or obesity. These findings expand our understanding of factors that maintain human reproductive health and lend insight into the domestication of retrotransposon-derived genes.
3D chromatin maps of a brown alga reveal U/V sex chromosome spatial organization
Authors: Liu Pengfei , Vigneau Jeromine , Craig Rory , Barrera-Redondo Josue , Avdievich Elena , Martinho Claudia , Borg Michael , Haas Fabian B. , Liu Chang , Coelho Susana M 
Published: May 2024

AbstractSex chromosomes are unique genomic regions displaying structural and evolutionary features that distinguish them markedly from autosomes. Although nuclear three dimensional (3D) folding of chromatin structure is im-portant for gene expression regulation and correct developmental programs, very little is known about the 3D architecture of sex chromosomes within the nucleus, and how that impacts their function in sex determination. Here, we determine the sex-specific 3D organization of the model brown algaEctocarpuschromosomes at 2 kb resolution, by comprehensively mapping long-range chromosomal interactions using Hi-C coupled with Oxford Nanopore long reads. We report thatEctocarpusinterphase chromatin exhibits a non-Rabl conformation, with strong contacts among telomeres and among centromeres, which feature centromere-specific LTR retrotranspos-ons. TheEctocarpuschromosomes do not contain large local interactive domains that resemble TADs described in animals, but their 3D genome organization is largely shaped by post-translational modifications of histone pro-teins that regulate chromatin compaction and mediate transcriptional regulation. We describe the spatial confor-mation and sub-nuclear positioning of the sex determining region (SDR) within the U and V chromosomes and show that these regions are very insulated and span the centromeres. Moreover, we link sex-specific chromatin dynamics and gene expression levels to the 3D chromatin structure of U and V chromosomes. Finally, we uncover the unique conformation of a large genomic region on chromosome 6 harboring an endogenous viral element (EVE), providing insights regarding the functional significance of the chromatin organisation of latent giant dsDNA virus.