Miracle-dz/UniFAR-FTUs huggingface dataset:
A statistical framework for powerful multi-trait rare variant analysis in large-scale whole-genome sequencing studies

Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally-scalable analytical pipeline for functionally-informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple traits, and further empowers rare variant association analysis by incorporating multiple functional annotations. We applied MultiSTAAR to jointly analyze three lipid traits (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) in 61,861 multi-ethnic samples from the Trans-Omics for Precision Medicine (TOPMed) Program. We discovered new associations with lipid traits missed by single-trait analysis, including rare variants within an enhancer of NIPSNAP3A and an intergenic region on chromosome 1.
Inferring therapeutic vulnerability within tumors through integration of pan-cancer cell line and single-cell transcriptomic profiles

Single-cell RNA sequencing greatly advanced our understanding of intratumoral heterogeneity through identifying tumor subpopulations with distinct biologies. However, translating biological differences into treatment strategies is challenging, as we still lack tools to facilitate efficient drug discovery that tackles heterogeneous tumors. One key component of such approaches tackles accurate prediction of drug response at the single-cell level to offer therapeutic options to specific cell subpopulations. Here, we present a transparent computational framework (nicknamed scIDUC) to predict therapeutic efficacies on an individual-cell basis by integrating single-cell transcriptomic profiles with large, data-rich pan-cancer cell line screening datasets. Our method achieves high accuracy, with predicted sensitivities easily able to separate cells into their true cellular drug resistance status as measured by effect size (Cohen’s d > 1.0). More importantly, we examine our method’s utility with three distinct prospective tests covering different diseases (rhabdomyosarcoma, pancreatic ductal adenocarcinoma, and castration-resistant prostate cancer), and in each our predicted results are accurate and mirrored biological expectations. In the first two, we identified drugs for cell subpopulations that are resistant to standard-of-care (SOC) therapies due to intrinsic resistance or effects of tumor microenvironments. Our results showed high consistency with experimental findings from the original studies. In the third test, we generated SOC therapy resistant cell lines, used scIDUC to identify efficacious drugs for the resistant line, and validated the predictions with in-vitro experiments. Together, scIDUC quickly translates scRNA-seq data into drug response for individual cells, displaying the potential as a first-line tool for nuanced and heterogeneity-aware drug discovery.
Parasite-mediated predation determines the infection in a complex predator-prey system

The interplay of host-parasite and predator-prey interactions is critical in ecological dynamics because both predators and parasites play an important role in regulating populations and communities. But what is the prevalence of infected prey and predators when a parasite is transmitted through trophic interactions, particularly when stochastic fluctuations of demographical changes are allowed arising from individual-level dynamics? Here, we analysed the system stability and the frequency of infected and uninfected host subpopulations in a complex predator-prey-parasite system, where infection happens through trophic interactions transmitting parasites from prey to predators. We varied the parasite virulence implemented as reproductive costs imposed on infected hosts and the probabilities of parasites infecting the hosts per encounter, to investigate how those important evolutionary factors will determine the species coexistence and population composition. We further explored the role of stochasticity in our system by comparing our deterministic analysis with stochastic simulations. Our results show that parasites go extinct when the infection probabilities of either host are small. The success in infecting the final host (the predator) is more critical for the survival of the parasite species, as the threshold for infection probability of the predator is higher than that of the prey for three-species coexistence. While our stochastic simulations agree with deterministic predictions well in most parameter regions. However, in the border parameter regions between coexistence and extinction typically with high infection probabilities, while only one possible outcome in deterministic dynamics, both coexistence and extinction can happen in stochastic repeats under the same parameter values. This illustrates the importance of stochasticity and demographic fluctuations in species coexistence. In addition, the proportion of infected individuals increases with the infection probabilities in our deterministic analysis and stochastic simulations as expected. Interestingly, we found that in some parameter space, the relative frequencies of infected and uninfected individuals are different between the intermediate host (prey) and the final host (predator) populations. This counterintuitive observation shows that the interplay of host-parasite and predator-prey interactions lead to more complex dynamics than a simple resource-consumer relationship.
Reactive Solute Transport in Streams: 1. Development of an Equilibrium‐Based Model

An equilibrium-based solute transport model is developed for the simulation of trace metal fate and transport in streams. The model is formed by coupling a solute transport model with a chemical equilibrium submodel based on MINTEQ. The solute transport model considers the physical processes of advection, dispersion, lateral inflow, and transient storage, while the equilibrium submodel considers the speciation and complexation of aqueous species, precipitation/dissolution and sorption. Within the model, reactions in the water column may result in the formation of solid phases (precipitates and sorbed species) that are subject to downstream transport and settling processes. Solid phases on the streambed may also interact with the water column through dissolution and sorption/desorption reactions. Consideration of both mobile (water-borne) and immobile (streambed) solid phases requires a unique set of governing differential equations and solution techniques that are developed herein. The partial differential equations describing physical transport and the algebraic equations describing chemical equilibria are coupled using the sequential iteration approach.
RNA isoform expression landscape of the human dorsal root ganglion (DRG) generated from long read sequencing

Splicing is a post-transcriptional RNA processing mechanism that enhances genomic complexity by creating multiple isoforms from the same gene. Diversity in splicing in the mammalian nervous system is associated with neuronal development, synaptic function and plasticity, and is also associated with diseases of the nervous system ranging from neurodegeneration to chronic pain. We aimed to characterize the isoforms expressed in the human peripheral nervous system, with the goal of creating a resource to identify novel isoforms of functionally relevant genes associated with somatosensation and nociception. We used long read sequencing (LRS) to document isoform expression in the human dorsal root ganglia (hDRG) from 3 organ donors. Isoforms were validated in silico by confirming expression in hDRG short read sequencing (SRS) data from 3 independent organ donors. 19,547 isoforms of protein-coding genes were detected using LRS and validated with SRS and strict expression cutoffs. We identified 763 isoforms with at least one previously undescribed splice-junction. Previously unannotated isoforms of multiple pain-associated genes, including ASIC3, MRGPRX1 and HNRNPK were identified. In the novel isoforms of ASIC3, a region comprising ∼35% of the 5’UTR was excised. In contrast, a novel splice-junction was utilized in isoforms of MRGPRX1 to include an additional exon upstream of the start-codon, consequently adding a region to the 5’UTR. Novel isoforms of HNRNPK were identified which utilized previously unannotated splice-sites to both excise exon 14 and include a sequence in the 5’ end of exon 13. The insertion and deletion in the coding region was predicted to excise a serine-phosphorylation site favored by cdc2, and replace it with a tyrosine-phosphorylation site potentially phosphorylated by SRC. We also independently confirm a recently reported DRG-specific splicing event in WNK1 that gives insight into how painless peripheral neuropathy occurs when this gene is mutated. Our findings give a clear overview of mRNA isoform diversity in the hDRG obtained using LRS. Using this work as a foundation, an important next step will be to use LRS on hDRG tissues recovered from people with a history of chronic pain. This should enable identification of new drug targets and a better understanding of chronic pain that may involve aberrant splicing events.
MiceVAPORDot: A novel automated approach for high-throughput behavioral characterization during E-cigarette exposure in mice

The prosperity of electronic nicotine delivery systems (ENDS) or e-cigarette use has been regarded to lead an increasing risk of nicotine addiction, especially among youth. Understanding and evaluating the behaviors induced by ENDS are fundamental to the study of neuropsychiatric effects of e-cigarettes. However, little is known regarding the behavioral features during e-cigarette exposure in mice. Current behavioral assessments for nicotine addiction are based on nicotine withdrawal-induced anxiety which can be only performed after ENDS exposures. Here we developed MiceVAPORDot, a novel high-throughput tool for automated in situ behavioral characterization during e-cigarette exposure. The integration of a deep learning-based animal pose tracking method by MiceVAPORDot allows precise characterization on behavioral phenotypes of e-vapor exposed mice, which were unable revealed by traditional evaluation methodology such as conditioned place preference and elevated plus maze tests. The behavioral fingerprints recognized by MiceVAPORDot can be used for high-throughput screening on incentive nature of e-cigarette flavors as well as medications for smoking cessation.
Mixed signatures for subcritical dynamics in rodent hippocampus during sleep and awake epochs

Neuronal dynamics such as brain criticality have recently been attributed to optimal information processing. Brain criticality attempts to elucidate the collective dynamics of a large number of neurons. It posits that the brain operates near critical to the critical point, although the field is rife with controversies and contrasting evidence. Similar computational capacities are observed during sharp wave ripples in the hippocampus prompting the need to correlate their dynamics. In the current study, the measures of avalanche criticality including neuronal avalanches, branching process, crackling noise relation, and deviation from criticality coefficient and Hurst exponents for long-range temporal correlations in rodent hippocampus during sharp wave ripples are reported. The evidence for mixed subcritical to critical dynamics in the hippocampus and minimal difference between ripple and no ripple times across measured metrics was found. The evidence demonstrates heterogeneity in signatures of criticality among animals and brain areas, indicating the presence of broad-range neuronal dynamics.
The role of task on the human brain’s responses to, and representation of, visual regularity defined by reflection and rotation

Identifying and segmenting objects in an image is generally achieved effortlessly and is facilitated by the presence of symmetry: a principle of perceptual organisation used to interpret sensory inputs from the retina into meaningful representations. However, while imaging studies show evidence of symmetry selective responses across extrastriate visual areas in the human brain, whether symmetry is processed automatically is still under debate. We used functional Magnetic Resonance Imaging (fMRI) to study the response to and representation of two types of symmetry: reflection and rotation. Dot pattern stimuli were presented to 15 human participants (10 female) under stimulus-relevant (symmetry) and stimulus-irrelevant (luminance) task conditions. Our results show that symmetry-selective responses emerge from area V3 and extend throughout extrastriate visual areas. This response is largely maintained when participants engage in the stimulus irrelevant task, suggesting an automaticity to processing visual symmetry. Our multi-voxel pattern analysis (MVPA) results extend these findings by suggesting that not only spatial organisation of responses to symmetrical patterns can be distinguished from that of non-symmetrical (random) patterns, but also that representation of reflection and rotation symmetry can be differentiated in extrastriate and object-selective visual areas. Moreover, task demands did not affect the neural representation of the symmetry information. Intriguingly, our MVPA results show an interesting dissociation: representation of luminance (stimulus irrelevant feature) is maintained in visual cortex only when task relevant, while information of the spatial configuration of the stimuli is available across task conditions. This speaks in favour of the automaticity for processing perceptual organisation: extrastriate visual areas compute and represent global, spatial properties irrespective of the task at hand. Key Points Symmetry selective responses observed in extrastriate visual cortex but not V1 whether stimulus spatial configuration is task relevant or irrelevant. Representation for reflection and rotation differ in extrastriate and object-selective areas, during both stimulus relevant and irrelevant tasks. Representation of luminance information is available only when task relevant.
pathCLIP: Detection of Genes and Gene Relations from Biological Pathway Figures through Image-Text Contrastive Learning

In biomedical literature, biological pathways are commonly described through a combination of images and text. These pathways contain valuable information, including genes and their relationships, which provide insight into biological mechanisms and precision medicine. Curating pathway information across the literature enables the integration of this information to build a comprehensive knowledge base. While some studies have extracted pathway information from images and text independently, they often overlook the correspondence between the two modalities. In this paper, we present a pathway figure curation system named pathCLIP for identifying genes and gene relations from pathway figures. Our key innovation is the use of an image-text contrastive learning model to learn coordinated embeddings of image snippets and text descriptions of genes and gene relations, thereby improving curation. Our validation results, using pathway figures from PubMed, showed that our multimodal model outperforms models using only a single modality. Additionally, our system effectively curates genes and gene relations from multiple literature sources. A case study on extracting pathway information from non-small cell lung cancer literature further demonstrates the usefulness of our curated pathway information in enhancing related pathways in the KEGG database.
Environmental controls on coral skeletal δ13C in the northern South China Sea

In this paper, we investigate the relationship between seasonal climatic and environmental variables, and the skeletal δ13C of modern and mid‐Holocene Porites lutea corals from the southern coast of Hainan Island in the northern South China Sea. No significant correlations were observed between δ13C in the modern coral and solar insolation or sea surface temperature. However, seasonal variability of δ13C in the modern coral covaries with rainfall on Hainan Island. Furthermore, the seasonal variations of δ13C in both the modern and mid‐Holocene coral are synchronous with those of the coral Δδ18O, which is a proxy for seawater δ18O and, in turn, largely controlled by local rainfall. These observations suggest that coral δ13C variations are closely associated with rainfall in this region. Given that river runoff contains dissolved inorganic carbon (DIC) with a negative δ13C, we suggest that periods of high rainfall on Hainan Island deliver increased amounts of 13C‐depleted DIC to coastal seawater, resulting in an enhanced negative δ13C in the corals. Our findings, together with previous studies, appear to demonstrate that in coastal environments, coral skeletal δ13C levels are controlled mainly by terrestrial carbon input and are significantly influenced by terrestrial river runoff. Consequently, the geochemical interpretation of coral δ13C records may differ between coastal areas and offshore areas or the open ocean.
Alternative Way for Determination of Yields Stress as Rheology Parameter for Mudflow

To understand the behavior of mudflow as one of notorious mass movement in geotechnical engineering, two rheology parameters should be obtained as yield stress and viscosity. Water content for mudflow could be equal to or higher than liquid limit. Viscosity could be obtained using a flow box test. Flow box test uses couple theory from Terzaghi's trap door and Bingham model. There is a limitation for flow box test that it needs yield stress (i.e., undrained cohesion) value for deriving viscosity. Hence, fall cone penetration test could be used to determine yield stress by using the empirical equation based on its penetration. This test uses 80 g of cone with 30 o cone angle. In this paper, the authors use kaolin, bentonite, Parakan Muncang, and Cipali. The range of water content of each soil is from plastic limit and over liquid limit. The results show that the shear strength of kaolin and Parakan Muncang is higher than bentonite and Cipali. This may due to the type of soil mineral. Hence, the viscosity derived from flow box test show the same results that the viscosity of kaolin and Parakan Muncang is higher than two other soils. All of the viscosities are in the range of published viscosity database. Hence, fall cone penetration test could be used to determine yield stress as rheology parameter for mudflow.
Rapid Advance of Spring Arrival Dates in Long-Distance Migratory Birds

Several bird species have advanced the timing of their spring migration in response to recent climate change. European short-distance migrants, wintering in temperate areas, have been assumed to be more affected by change in the European climate than long-distance migrants wintering in the tropics. However, we show that long-distance migrants have advanced their spring arrival in Scandinavia more than short-distance migrants. By analyzing a long-term data set from southern Italy, we show that long-distance migrants also pass through the Mediterranean region earlier. We argue that this may reflect a climate-driven evolutionary change in the timing of spring migration.
REGIONAL PATTERNS OF SEA SURFACE TEMPERATURE RISE: IMPLICATIONS FOR GLOBAL OCEAN CIRCULATION CHANGE AND THE FUTURE OF CORAL REEFS AND FISHERIES

Since the 1980s, corals have undergone unprecedented high temperature mass bleaching and mortality. Locations, intensity, and severity of bleaching are predictable by the sea surface temperature (SST) "HotSpot" method (Goreau & Hayes, 1994). HotSpot patterns over the last 2 decades show strong regional trends: SST increases are many times average rates in some regions, but lower in others. The regional spatial HotSpot patterns suggest that ocean circulation is being systematically altered by world-wide changes in winds, ocean currents, and upwelling. The data suggest that: 1) intensities of all warm currents are increasing; 2) intensities of all cold currents are decreasing; 3) coastal upwelling is being reduced at all major sites; 4) open-ocean upwelling is increasing in the interiors of all ocean basins; 5) wind driven upwelling is increasing all around Antarctica; and 6) flow from the Pacific to the Indian Ocean through Indonesia is increasing. Because of their magnitude, these changes will have much greater effects on regional climatic extremes and ecosystem alterations than mean global warming rates. The most rapidly warming areas are potential sites of regional coral reef ecosystem collapse. Corals may survive in areas where warming is slowest due to increased upwelling. However they will persist in marginal coral communities, not constructional coral reefs, due to increased competition from algae and filter feeders. These changes have strong implications for future patterns of global warming, ocean-atmosphere CO2 fluxes, marine biodiversity, fisheries catches, and primary productivity. Pelagic fisheries should be displaced from intense coastal upwelling zones to less productive open-ocean upwelling areas, with
CHEMICAL COMPOSITION OF OPEN POLLINATED AND HYBIRD POPULLATION OF SUNFLOWER (HELIANTHUS ANNUUS L.)

Sunflower is the world fourth most important sources of edible oil. A lot of work has been done for varietals improvement through conventional breeding in Pakistan. Sunflower is the cash crop and is easily adapted to many region of Pakistan, genetic and agronomical improvement was needed so that economically valuable crop could be harvested. In the present work, 16 cultivars (open pollinated population “OPP” and hybrid population “HP” eight each) of sunflower was evaluated. The study was aimed at evaluating the mineral composition, estimation of moisture contents, measuring electrical conductivity and 100 seeds weight. The mineral composition was fractionated though Atomic Absorption Spectrometer, which indicate that Zn +2 was 8.54 and 9.35%; Cu +2 0.5 and 0.02%; Mn +2 3.48 and 9.72%; Co +2 18.67 and 16.81%; Mg +2 68.27 and 83.53%; Fe +3 4.32 and 4.35% were estimated in HP and OPP respectively. Similarly, moisture contents 6.26 and 6.78%, and 1000-seeds weight 510.8 and 598g were calculated in the HP and OPP respectively. In comparative picture the mineral concentration, moisture contents and 100 seeds weight in open pollinated population were high as compared to hybrid. A total of 11.7 % genetic diversity was observed in mineral composition of both the populations. The EC was high in HP ranging from 70. 85–137.8, while comparatively low in OPP ranged 46.81 – 120.18.