bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncover spatially informed shared variations for single-cell spatial transcriptomics with STew
Authors: Guo Nanxi , Vargas Juan , Fritz Douglas , Krishna Revanth , Zhang Fan 
Published: October 2023

AbstractMotivationThe recent spatial transcriptomics (ST) technologies have enabled characterization of gene expression patterns and spatial information, advancing our understanding of cell lineages within diseased tissues. Several analytical approaches have been proposed for ST data, but effectively utilizing spatial information to unveil the shared variation with gene expression remains a challenge.ResultsWe introduce STew, a Spatial Transcriptomic multi-viEW representative learning method, to jointly analyze spatial information and gene expression in a scalable manner, followed by a data-driven statistical framework to measure the goodness of model fit. Through benchmarking using Human DLPFC data with true manual annotations, STew achieved superior performance in both clustering accuracy and continuity of identified spatial domains compared with other methods. STew is also robust to generate consistent results insensitive to model parameters, including sparsity constraints. We next applied STew to various ST data acquired from 10x Visium and Slide-seqV2, encompassing samples from both mouse and human brain, which revealed spatially informed cell type clusters. We further identified a pro-inflammatory fibroblast spatial niche using ST data from psoriatic skins. Hence, STew is a generalized method to identify both spatially informed clusters and disease-relevant niches in complex tissues.AvailabilitySource code and the R software tool STew are available fromgithub.com/fanzhanglab/STew.Contactfan.3.zhang@cuanschutz.eduSupplementary informationSupplementary data are provided.
Multiomics-assisted characterization of rice-Yellow Stem Borer interaction provides genomic and mechanistic insights into stem borer tolerance in rice
Authors: Gokulan C. G. , Bangale Umakanth , Balija Vishalakshi , Ballichatla Suneel , Potupureddi Gopi , Rao Deepti , Varma Prashanth , Magar Nakul , Karteek J. , Sravan M. , Padmakumari A. P. , Laha Gouri S , Rao LV Subba , Barbadikar Kalyani M. , Raman Meenakshi Sundaram , Patel Hitendra K. , Madhav M Sheshu , Sonti Ramesh V. 
Published: October 2023

SUMMARYYellow stem borer (YSB),Scirpophaga incertulas(Walker) (Lepidoptera: Crambidae), is a major pest of rice in India, that can lead to 20-60% loss in rice production. Effective management of YSB infestation is challenged by the non-availability of adequate source of resistance and poor understanding of resistance mechanisms, thus necessitating studies for generating resources to breed YSB resistant rice and to understand rice-YSB interaction. In this study, by using bulk-segregant analysis in combination with next-generation sequencing, Quantitative Trait Loci (QTL) intervals in five rice chromosomes were mapped that could be associated with YSB tolerance at vegetative phase in a highly tolerant rice line named SM92. Further, multiple SNP markers that showed significant association with YSB tolerance in rice chromosomes 1, 5, 10, and 12 were developed. RNA-sequencing of the susceptible and tolerant lines revealed multiple genes present in the candidate QTL intervals to be differentially regulated upon YSB infestation. Comparative transcriptome analysis revealed a putative candidate gene that was predicted to encode an alpha-amylase inhibitor. Analysis of the transcriptome and metabolite profiles further revealed a possible link between phenylpropanoid metabolism and YSB tolerance. Taken together, our study provides insights on rice-YSB interaction at genomic, transcriptomic and metabolomic level, thereby facilitating the understanding of tolerance mechanism. Importantly, a promising breeding line and markers for YSB tolerance have been developed that can potentially aid in marker-assisted breeding of YSB resistance among elite rice cultivars.SIGNIFICANCE STATEMENTGlobal rice production is threatened by various pests, among which stem borers pose serious challenges. Hence, understanding the molecular intricacies of rice-stem borer interaction is necessary for effective pest management. Here, we used a multi-omics approach to unravel the mechanisms that might help rice combat yellow stem borer infestation, thus providing insights and scope for developing YSB tolerant rice varieties. To facilitate the latter, we developed markers that co-segregate with tolerance.
MurSS: Multi-resolution Selective Segmentation Model for Breast Cancer
Authors: Lee Joonho , Lee Geongyu , Kwak Tae-Young , Kim Sunwoo , Jin Min-Sun , Kim Chungyeul , Chang Hyeyoon 
Published: October 2023

AbstractWe propose the Multi-resolution Selective Segmentation model (MurSS) for segmenting benign, Ductal Carcinoma In Situ, and Invasive Ductal Carcinoma in breast resection Hematoxylin and Eosin stained Whole Slide Images. MurSS simultaneously trains on context information from a wide area at low resolution and content information from a local area at high resolution, aiming for a more accurate diagnosis. Additionally, through the selection stage, it provides solutions for ambiguous tissue regions. Our proposed MurSS achieves a mean Intersection of Union performance of 91.1%, which is at least 16.8% and at most 19.0% higher than well-known image segmentation models.
ViCEKb: Vitiligo-linked Chemical Exposome Knowledgebase
Authors: Chivukula Nikhil , Ramesh Kundhanathan , Subbaroyan Ajay , Sahoo Ajaya Kumar , Dhanakoti Gokul Balaji , Ravichandran Janani , Samal Areejit 
Published: October 2023

AbstractVitiligo is a complex disease wherein the environmental factors, in conjuction with the underlying genetic predispositions, trigger the autoimmune destruction of melanocytes, ultimately leading to depigmented patches on the skin. Apart from being susceptible to other autoimmune disorders, the affected patients may face social stigmatization leading to a decreased quality in life. While genetic factors have been extensively studied, the knowledge on environmental triggers remains sparse and less understood. Therefore, a comprehensive understanding of the environemental triggers will not only explain the complex etiology of the disease, it will also enable the prioritization of potential toxic chemicals in human chemcical exposome. Towards this, we present the first comprehensive knowledgbase of vitiligo triggering chemicals compiled from published literature namely, Vitiligo-linked Chemical Exposome Knowledgbase (ViCEKb). ViCEKb involved an extensive and systematic manual effort in curation of published literature and subsequent compilation of 113 unique chemical triggers of vitiligo. ViCEKb standardises various chemical information, and categorizes the chemicals based on their evidences and sources of exposure. Importantly, ViCEKb contains a wide range of metrics necessary for different toxicological evaluations. Moreover, our extensive cheminformatics-based analysis of the ViCEKb chemical space highlighted its diversity and uniqueness in comparison to other skin specific chemical regulatory lists. We also observed that ViCEKb chemicals are present in various consumer products and are not regulated. Additionally, a transcriptomics based analysis of ViCEKb chemical perturbations in skin cell samples highlighted the commonality in their linked biological processes. Overall, we present the first comprehensive effort in compilation and exploration of various chemical triggers of vitiligo. We believe such a resource will enable in deciphering the complex etiology of vitiligo and aid in the characterization of human chemical exposome. ViCEKb is freely available for academic research at:https://cb.imsc.res.in/vicekb.
Effects of habitat and fruit scent on the interactions between short-tailed fruit bats andPiperplants
Authors: Sil Sneha , Visconti Flo , Chaverri Gloriana , Santana Sharlene E. 
Published: October 2023

AbstractPiperis a mega-diverse genus of pioneer plants that contributes to the maintenance and regeneration of tropical forests. With deforestation and climate change threatening forest ecosystems, understanding the mutualism betweenPiperand its seed dispersers becomes especially important. In the Neotropics,Carolliabats use olfaction to forage forPiperfruit and are a main disperser ofPiperseeds via consumption and subsequent defecation during flight. In return,Piperfruits provide essential nutrients forCarolliayear-round. There is evidence that the types and diversity ofPiperfrugivores are influenced by the primary habitat of differentPiperspecies (forest, gap), with forestPiperdepending more on bats for seed dispersal; however, this pattern has not been tested broadly. We aimed to characterize and compare the interactions betweenCarolliaandPiperacross forested and gap habitats, and further investigate whether differences in fruit traits relevant to bat foraging (i.e., scent) could underlie differences inCarollia-Piperinteractions. We collected nightly acoustic ultrasonic recordings and 24h camera trap data in La Selva, Costa Rica across 12 species ofPiper(6 forest, 6 gap) and integrated this information with data onCarolliadiet andPiperfruit scent. Merging biomonitoring modalities allowed us to characterize ecological interactions in a hierarchical manner: from general activity and presence of bats, to visitations and inspections of plants, to acquisition and consumption of fruits. We found significant differences inCarollia-Piperinteractions between forested and gap habitats; however, the type of biomonitoring modality (camera trap, acoustics, diet) influenced our ability to detect these differences. ForestPiperwere exclusively visited by bats, whereas gapPiperhad a more diverse suite of frugivores; the annual diet ofCarollia, however, is dominated by gapPipersince these plants produce fruit year-round. We found evidence that fruit scent composition significantly differs between forest and gapPiper, which highlights the possibility that bats could be using chemical cues to differentially forage for gap versus forestPiper. By integrating studies ofPiperfruit scent, plant visitation patterns, andCarolliadiet composition, we paint a clearer picture of the ecological interactions betweenPiperandCarollia, and plant-animal mutualisms more generally.
vcfpp: a C++ API for rapid processing of the Variant Call Format
Authors: Li Zilong 
Published: October 2023

AbstractGiven the widespread use of the variant call format (VCF/BCF) coupled with continuous surge in big data, there remains a perpetual demand for fast and flexible methods to manipulate these comprehensive formats across various programming languages. Many bioinformatic tools were developed in C++ to ensure high performance and modern C++ standards offer an ever expanding libraries to ease program development. This work presents vcfpp, a C++ API of HTSlib in a single file, providing an intuitive interface to manipulate VCF/BCF files rapidly and safely, in addition to being portable. Moreover, this work introduces the vcfppR package to demonstrate the development of a high performance R package with vcfpp, allowing for rapid and straightforward variants analyses. In the benchmarking, with the compressed VCF of 3202 samples and one million variants as input, the dynamic script using vcfppR is only 1.3×slower than its compiled C++ counterpart vcfpp, whereas the Python API cyvcf2 is 1.9×slower when streaming a variant analysis with little memory. Lastly, in a two-step setting where the whole VCF content is loaded first, vcfppR demonstrates a 101×speed improvement over vcfR and even more folds than data.table in processing genotypes.
Pan-cancer evolution signatures link clonal expansion to dynamic changes in the tumour immune microenvironment
Authors: Yang Xinyu , Liu Wei , Macintyre Geoff , Van Loo Peter , Markowetz Florian , Bailey Peter , Yuan Ke 
Published: October 2023

ABSTRACTCancer is an evolutionary process characterised by profound intra-tumour heterogeneity. Intra-tumour heterogeneity can be quantified using in silico estimates of cancer cell fractions of tumour-specific somatic mutations. Here we demonstrate a data-driven approach that uses cancer cell fraction distributions to identify 4 robust pan-cancer evolutionary signatures from an analysis of 4,146 individual tumour samples (TCGA) representing 17 distinct cancer types. Evolutionary signatures defined a continuum of cancer cell fractions representing neutral evolution, clonal expansion and fixation. Correlation of evolutionary signatures with programs representing distinct mutational and biological processes demonstrated that individual tumours enriched for clonal expansions and fixations were associated with immune evasion and distinct changes in the tumour immune microenvironment. We observed a dynamic switch between adaptive and innate immune processes as tumours undergo clonal fixation and escape immune surveillance. We also identify mutational processes underpinning different modes of tumour evolution and demonstrate that switching between adaptive and innate immune cell populations is accompanied by the clonal expansion of driver genes that modulate tumour-stroma interactions1.
Manganese homeostasis modulates fungal virulence and stress tolerance inCandida albicans
Authors: Henry Manon , Khemiri Inès , Tebbji Faiza , Abu-Helu Rasmi , Vincent Antony T , Sellam Adnane 
Published: October 2023

AbstractDue to the scarcity of transition metals within the human host, fungal pathogens have evolved sophisticated mechanisms to uptake and utilize these micronutrients at the infection interface. While considerable attention was turned to iron and copper acquisition mechanisms and their importance in fungal fitness, less was done regarding either the role of manganese (Mn) in infectious processes or the cellular mechanism by which fungal cells achieve their Mn- homeostasis. Here, we undertook transcriptional profiling in the pathogenic fungusCandida albicansexperiencing both Mn starvation and excess to capture biological processes that are modulated by this metal. We uncovered that Mn scarcity influences diverse processes associated with fungal fitness including invasion of host cells and antifungal sensitivity. We show that Mn levels influence the abundance of iron and zinc emphasizing the complex crosstalk between metals. Deletion ofSMF12, a member of Mn Nramp transporters confirmed its contribution to Mn uptake.smf12was unable to form hyphae and damage host cells and exhibited sensitivity to azoles. We found that the unfolded protein response (UPR), likely activated by decreased glycosylation under Mn limitation, was required to restore growth when cells were shifted from a Mn-starved to a Mn-repleted medium. RNA-seq profiling of cells exposed to Mn excess revealed that UPR was also activated. Furthermore, the UPR signaling axis Ire1-Hac1 was required to bypass Mn toxicity. Collectively, this study underscores the importance of Mn homeostasis in fungal virulence, and comprehensively provides a portrait of biological functions that are modulated by Mn in a fungal pathogen.
Epigenetic differences between wild and cultivated grapevines highlight the contribution of DNA methylation during crop domestication
Authors: Rodriguez-Izquierdo Alberto , Carrasco David , Anand Lakshay , Magnani Roberta , Catarecha Pablo , Arroyo-Garcia Rosa , Rodriguez Lopez Carlos M. 
Published: October 2023

AbstractThe domestication process in grapevine facilitated the fixation of desired traits. The vegetative propagation of grapevines through cuttings has allowed for easier preservation of these genotypes compared to sexual reproduction. Nonetheless, even with vegetative propagation, different phenotypes often emerge within the same vineyard due to potential genetic somatic mutations in the genome. These mutations, however, are not the sole factors influencing phenotype. Alongside somatic variations, epigenetic variation has been proposed as pivotal player in regulating phenotypic variability acquired during domestication. The emergence of these epialleles might have significantly influenced grapevine domestication over time. This study aims to investigate the impact of the domestication process on the methylation patterns in cultivated grapevines. Reduced-representation bisulphite sequencing was conducted on 18 cultivated and wild accessions. Results revealed that cultivated grapevines exhibited higher methylation levels than their wild counterparts. Differential Methylation Analysis between wild and cultivated grapevines identified a total of 9955 differentially methylated cytosines, of which 78% where hypermethylated in cultivated grapevines. Functional analysis shows that core methylated genes (those consistently methylated in wild and cultivated accessions) are associated to stress response and terpenoid/isoprenoid metabolic processes. While genes presenting differential methylation are associated with proteins targeting to the peroxisome, ethylene regulation, histone modifications, and defense response. Additionally, our findings reveal that environmentally induced DNA methylation patterns are, at least partially, guided by the region of origin of wild grapevine accessions. Collectively, our results shed light on the pivotal roles that epialleles might have played throughout the domestication history of grapevines.
Engineered dsRNA-protein nanoparticles for effective long-distance transport, delivery and gene silencing in plants
Authors: Sun Huayu , Kalluri Ankarao , Tang Dan , Ding Jingwen , Zhai Longmei , Gu Xianbin , Li Yanjun , Yer Huseyin , Yang Xiaohan , Tuskan Gerald A. , Deng Zhanao , Gmitter Frederick G. , Duan Hui , Kumar Challa , Li Yi 
Published: October 2023

AbstractLong-distance transport of exogenous biologically active RNA molecules in higher plants has not been reported. Here, we report that cationized bovine serum albumin (cBSA) avidly binds double-stranded beta-glucuronidase RNA (dsGUS RNA) to form nucleic acid-protein nanocomplexes. Using tobacco and poplar plants, we have shown effective uptake and long-distance transport of cBSA/dsGUS RNA nanocomplexes from basal ends of leaf petioles to leaf blades as well as from basal ends of shoots to their apexes and apical leaves. We have further demonstrated that the cBSA/dsGUS RNA nanocomplexes are highly effective in silencing both conditionally inducibleDR5-GUSgene and constitutively active35S-GUSgene in leaf, shoot and shoot meristem tissues. This cBSA/dsRNA delivery technology may provide a convenient, fast, and inexpensive tool for characterizing gene functions in plants, and potentially forin plantagene-editing.
EWA-DB, Slovak Database of Speech Affected by Neurodegenerative Diseases
Authors: Rusko Milan , Sabo Róbert , Trnka Marián , Zimmermann Alfréd , Malaschitz Richard , Ružický Eugen , Brandoburová Petra , Kevická Viktória , Škorvánek Matej 
Published: October 2023

AbstractA new Slovak speech database EWA-DB was created for research purposes aimed at early detection of neurodegenerative diseases from speech. It contains 1649 speakers performing various speech and language tasks, such as sustained vowel phonation, diadochokinesis, naming and picture description. The sample of speakers consists of individuals with Alzheimer’s disease, mild cognitive impairment, Parkinson’s disease, and healthy controls. In this article we describe the EWA-DB development process, the language and speech task selection, patient and healthy control recruitment, as well as the testing and recording protocol. The structure and content of the database and file formats are described in detail. We assume that the presented database could be suitable for the development of automatic systems predicting the diagnoses of Alzheimer’s disease, mild cognitive impairment, and Parkinson’s disease from language and speech features.
Connectivity changes following transcranial alternating current stimulation at 5-Hz: an EEG study
Authors: Lee Tien-Wen , Li Chiang-Shan R. , Tramontano Gerald 
Published: October 2023

ABSTRACTIntroductionTranscranial alternating current stimulation (tACS) at 5-Hz to the right hemisphere can alleviate anxiety symptoms. This study aimed to explore the connectivity changes following the treatment.MethodsWe collected electroencephalography (EEG) data from 24 participants with anxiety disorders before and after the tACS treatment during a single session. Electric stimulation was applied over the right hemisphere, with 1.0 mA at F4, 1.0 mA at P4, and 2.0 mA at T8, following the 10-10 EEG convention. With eLORETA, the scalp signals were transformed into the cortex’s current source density. We assessed the connectivity changes at theta frequency between the centers of Brodmann area (BA) 6/8 (frontal), BA 39/40 (parietal), and BA 21 (middle temporal). Functional connectivity was indicated by lagged coherences and lagged phase synchronization. Paired t-tests were used to quantify the differences statistically.ResultsWe observed enhanced lagged phase synchronization at theta frequency between the frontal and parietal regions and between the parietal and temporal regions.ConclusionApplying tACS 5-Hz over the right hemisphere enhanced inter-regional interaction, which was spectrum-specific and mainly mediated by phase, rather than power, synchrony. The potential neural mechanisms are discussed.
N6-methyladenosine modification is not a general trait of viral RNA genomes
Authors: Baquero-Perez Belinda , Yonchev Ivaylo D , Delgado-Tejedor Anna , Medina Rebeca , Puig-Torrents Mireia , Sudbery Ian , Begik Oguzhan , Wilson Stuart A , Maria Novoa Eva , Díez Juana 
Published: October 2023

AbstractDespite the nuclear localization of the m6A machinery, the genomes of multiple exclusively-cytoplasmic RNA viruses, such as chikungunya (CHIKV) and dengue (DENV), are reported to be extensively m6A-modified. However, these findings are mostly based on m6A-seq, an antibody-dependent technique with a high rate of false positives. Here, we addressed the presence of m6A in CHIKV and DENV RNAs. For this, we combined m6A-seq and the antibody-independent SELECT and nanopore direct RNA sequencing techniques with functional, molecular, and mutagenesis studies. Following this comprehensive analysis, we found no evidence of m6A modification in CHIKV or DENV transcripts. Furthermore, depletion of key components of the host m6A machinery did not affect CHIKV or DENV infection. Moreover, CHIKV or DENV infection had no effect on the m6A machinery’s localization. Our results challenge the prevailing notion that m6A modification is a general feature of cytoplasmic RNA viruses and underscore the importance of validating RNA modifications with orthogonal approaches.