Adjusting for genetic confounders in transcriptome-wide association studies improves discovery of risk genes of complex traits

Many methods have been developed to leverage expression quantitative trait loci (eQTL) data to nominate candidate genes from genome-wide association studies. These methods, including colocalization, transcriptome-wide association studies (TWAS) and Mendelian randomization-based methods; however, all suffer from a key problem—when assessing the role of a gene in a trait using its eQTLs, nearby variants and genetic components of other genes’ expression may be correlated with these eQTLs and have direct effects on the trait, acting as potential confounders. Our extensive simulations showed that existing methods fail to account for these ‘genetic confounders’, resulting in severe inflation of false positives. Our new method, causal-TWAS (cTWAS), borrows ideas from statistical fine-mapping and allows us to adjust all genetic confounders. cTWAS showed calibrated false discovery rates in simulations, and its application on several common traits discovered new candidate genes. In conclusion, cTWAS provides a robust statistical framework for gene discovery

GoM DE: interpreting structure in sequence count data with differential expression analysis allowing for grades of membership

Parts-based representations, such as non-negative matrix factorization and topic modeling, have been used to identify structure from single-cell sequencing data sets, in particular structure that is not as well captured by clustering or other dimensionality reduction methods. However, interpreting the individual parts remains a challenge. To address this challenge, we extend methods for differential expression analysis by allowing cells to have partial membership to multiple groups. We call this grade of membership differential expression (GoM DE). We illustrate the benefits of GoM DE for annotating topics identified in several single-cell RNA-seq and ATAC-seq data sets

Form-NLU: Dataset for the Form Language Understanding

Compared to general document analysis tasks, form document structure understanding and retrieval are challenging. Form documents are typically made by two types of authors; A form designer, who develops the form structure and keys, and a form user, who fills out form values based on the provided keys. Hence, the form values may not be aligned with the form designer's intention (structure and keys) if a form user gets confused. In this paper, we introduce Form-NLU, the first novel dataset for form structure understanding and its key and value information extraction, interpreting the form designer's intent and the alignment of user-written value on it. It consists of 857 form images, 6k form keys and values, and 4k table keys and values. Our dataset also includes three form types: digital, printed, and handwritten, which cover diverse form appearances and layouts. We propose a robust positional and logical relation-based form key-value information extraction framework. Using this dataset, Form-NLU, we first examine strong object detection models for the form layout understanding, then evaluate the key information extraction task on the dataset, providing fine-grained results for different types of forms and keys. Furthermore, we examine it with the off-the-shelf pdf layout extraction tool and prove its feasibility in real-world cases.Comment: Accepted by SIGIR 202

FusionFormer: A Multi-sensory Fusion in Bird's-Eye-View and Temporal Consistent Transformer for 3D Objection

Multi-sensor modal fusion has demonstrated strong advantages in 3D object detection tasks. However, existing methods that fuse multi-modal features through a simple channel concatenation require transformation features into bird's eye view space and may lose the information on Z-axis thus leads to inferior performance. To this end, we propose FusionFormer, an end-to-end multi-modal fusion framework that leverages transformers to fuse multi-modal features and obtain fused BEV features. And based on the flexible adaptability of FusionFormer to the input modality representation, we propose a depth prediction branch that can be added to the framework to improve detection performance in camera-based detection tasks. In addition, we propose a plug-and-play temporal fusion module based on transformers that can fuse historical frame BEV features for more stable and reliable detection results. We evaluate our method on the nuScenes dataset and achieve 72.6% mAP and 75.1% NDS for 3D object detection tasks, outperforming state-of-the-art methods

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Preparation of Hypophosphorous Acid by Bipolar Membrane Electrodialysis: Process Optimization and Phosphorous Acid Minimization

Hypophosphorous acid (H3PO2) is an important chemical product with wide applications in pharmaceuticals and electroless plating. In this study, bipolar membrane electrodialysis (BMED) was used to produce H3PO2 from sodium hypophosphite salt (NaH2PO2) to replace the traditional preparation methods. The BMED process was optimized in terms of current density, NaH2PO2 salt concentration, and initial NaOH concentration of the base solution. The results indicated that low Na+ leakage occurred at lower salt concentrations. Under the optimum conditions, such a BMED system obtained a high concentration of H3PO2, a low Na+ content, and a low energy consumption, equaling to 1.03 mol/L, 670 ppm, and 1.18 kW h/kg, respectively. To minimize the amount of phosphorous acid (H3PO3) generated from H3PO2 oxidation during the BMED process, a nitrogen aeration operation was applied in both the acid and salt chambers, decreasing the HPO32- content to 251 ppm, which was 44.1% lower than that without a dissolved oxygen content control strategy. The newly produced H3PO3 during the BMED process was reduced by 96.5%. The obtained results indicated that the BMED process has great potential for application in the production of high-quality H3PO2 from NaH2PO2 in industry

Impact of the magnetic field-assisted freezing on the moisture content, water migration degree, microstructure, fractal dimension, and the quality of the frozen tilapia

In this study, we determined the effect of a magnetic field applied during refrigeration in improving the quality of frozen tilapia. Alternating magnetic fields of 10 G, 20 G, 30 G, 40 G, and 50 G were applied during a low-temperature freezing treatment on the back, abdomen, and tail of tilapia. The control group was set at 0 G. A correlation analysis for the fish films after treating with different magnetic field strengths was carried out. The results showed that when the magnetic field was applied to assist freezing, the frozen quality of the tilapia was significantly improved, and the water separation and residual damage were reduced. The felled muscle tissue decreased, the fractal dimension value increased, the hardness decreased, and the elasticity increased. However, the impact of the magnetic field on the quality of the frozen tilapia did not change with an increase in the magnetic field strength. The effect on the back samples was more prominent when the fish were exposed to the magnetic field strength of 40 or 50 G. A magnetic field strength of 50 G was the most effective for the abdominal and tail samples. However, no significant difference was observed in the groups exposed to 10 and 20 G of magnetic fields

A new Bayesian factor analysis method improves detection of genes and biological processes affected by perturbations in single-cell CRISPR screening

Clustered regularly interspaced short palindromic repeats (CRISPR) screening coupled with single-cell RNA sequencing has emerged as a powerful tool to characterize the effects of genetic perturbations on the whole transcriptome at a single-cell level. However, due to its sparsity and complex structure, analysis of single-cell CRISPR screening data is challenging. In particular, standard differential expression analysis methods are often underpowered to detect genes affected by CRISPR perturbations. We developed a statistical method for such data, called guided sparse factor analysis (GSFA). GSFA infers latent factors that represent coregulated genes or gene modules; by borrowing information from these factors, it infers the effects of genetic perturbations on individual genes. We demonstrated through extensive simulation studies that GSFA detects perturbation effects with much higher power than state-of-the-art methods. Using single-cell CRISPR data from human CD8+ T cells and neural progenitor cells, we showed that GSFA identified biologically relevant gene modules and specific genes affected by CRISPR perturbations, many of which were missed by existing methods, providing new insights into the functions of genes involved in T cell activation and neurodevelopment