BioT5: Enriching Cross-modal Integration in Biology with Chemical Knowledge and Natural Language Associations

Recent advancements in biological research leverage the integration of molecules, proteins, and natural language to enhance drug discovery. However, current models exhibit several limitations, such as the generation of invalid molecular SMILES, underutilization of contextual information, and equal treatment of structured and unstructured knowledge. To address these issues, we propose $\mathbf{BioT5}$, a comprehensive pre-training framework that enriches cross-modal integration in biology with chemical knowledge and natural language associations. $\mathbf{BioT5}$ utilizes SELFIES for $100$ robust molecular representations and extracts knowledge from the surrounding context of bio-entities in unstructured biological literature. Furthermore, $\mathbf{BioT5}$ distinguishes between structured and unstructured knowledge, leading to more effective utilization of information. After fine-tuning, BioT5 shows superior performance across a wide range of tasks, demonstrating its strong capability of capturing underlying relations and properties of bio-entities. Our code is available at $\href{https://github.com/QizhiPei/BioT5}{Github}$.Comment: Accepted by Empirical Methods in Natural Language Processing 2023 (EMNLP 2023

Observation of giant circular dichroism induced by electronic chirality

Chiral phases of matter, characterized by a definite handedness, abound in nature, ranging from the crystal structure of quartz to spiraling spin states in helical magnets. In $1T$-TiSe$_2$ a source of chirality has been proposed that stands apart from these classical examples as it arises from combined electronic charge and quantum orbital fluctuations. This may allow its chirality to be accessed and manipulated without imposing either structural or magnetic handedness. However, direct bulk evidence that broken inversion symmetry and chirality are intrinsic to TiSe$_2$ remains elusive. Here, employing resonant elastic scattering of x-rays, we reveal the presence of giant circular dichroism up to $\sim$ 40$\%$ at forbidden Bragg peaks that emerge at the charge and orbital ordering transition. The dichroism varies dramatically with incident energy and azimuthal angle. Comparison to calculated scattering intensities unambiguously traces its origin to bulk chiral electronic order in ${\mathrm{TiSe}}_2$ and establishes resonant elastic x-ray scattering as a sensitive probe to electronic chirality.Comment: 6 pages, 4 figure

Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background DNA methylation has been linked to genome regulation and dysregulation in health and disease respectively, and methods for characterizing genomic DNA methylation patterns are rapidly emerging. We have developed/refined methods for enrichment of methylated genomic fragments using the methyl-binding domain of the human MBD2 protein (MBD2-MBD) followed by analysis with high-density tiling microarrays. This MBD-chip approach was used to characterize DNA methylation patterns across all non-repetitive sequences of human chromosomes 21 and 22 at high-resolution in normal and malignant prostate cells. Results Examining this data using computational methods that were designed specifically for DNA methylation tiling array data revealed widespread methylation of both gene promoter and non-promoter regions in cancer and normal cells. In addition to identifying several novel cancer hypermethylated 5' gene upstream regions that mediated epigenetic gene silencing, we also found several hypermethylated 3' gene downstream, intragenic and intergenic regions. The hypermethylated intragenic regions were highly enriched for overlap with intron-exon boundaries, suggesting a possible role in regulation of alternative transcriptional start sites, exon usage and/or splicing. The hypermethylated intergenic regions showed significant enrichment for conservation across vertebrate species. A sampling of these newly identified promoter (ADAMTS1 and SCARF2 genes) and non-promoter (downstream or within DSCR9, C21orf57 and HLCS genes) hypermethylated regions were effective in distinguishing malignant from normal prostate tissues and/or cell lines. Conclusions Comparison of chromosome-wide DNA methylation patterns in normal and malignant prostate cells revealed significant methylation of gene-proximal and conserved intergenic sequences. Such analyses can be easily extended for genome-wide methylation analysis in health and disease.Published versio

CEMIP Promotes Osteosarcoma Progression and Metastasis Through Activating Notch Signaling Pathway

Cell migration inducing protein (CEMIP) has been linked to carcinogenesis in several types of cancers. However, the role and mechanism of CEMIP in osteosarcoma remain unclear. This study investigated the role of CEMIP in the progression and metastasis of osteosarcoma, CEMIP was found to be overexpressed in osteosarcoma tissues when compared to adjacent non-tumor tissues, and its expression was positively associated with a poor prognosis in osteosarcoma patients. Silencing CEMIP decreased osteosarcoma cells proliferation, migration, and invasion, but enhanced apoptosis in vitro, and suppressed tumor growth and metastasis in vivo. Mechanistically, CEMIP promoted osteosarcoma cells growth and metastasis through activating Notch signaling pathway, silencing CEMIP would reduce the protein expression and activation of Notch/Jagged1/Hes1 signaling pathway in vitro and in vivo, activation of Notch signaling pathway could partially reversed cell proliferation and migration in shCEMIP osteosarcoma cells. In conclusion, our study demonstrated that CEMIP plays a substantial role in the progression of osteosarcoma via Notch signaling pathway, providing a promising therapeutic target in osteosarcoma

The Tianlai Cylinder Pathfinder array: System functions and basic performance analysis

The Tianlai Cylinder Pathfinder is a radio interferometer array designed to test techniques for 21 cm intensity mapping in the post-reionization Universe, with the ultimate aim of mapping the large scale structure and measuring cosmological parameters such as the dark energy equation of state. Each of its three parallel cylinder reflectors is oriented in the north-south direction, and the array has a large field of view. As the Earth rotates, the northern sky is observed by drift scanning. The array is located in Hongliuxia, a radio-quiet site in Xinjiang, and saw its first light in September 2016. In this first data analysis paper for the Tianlai cylinder array, we discuss the sub-system qualification tests, and present basic system performance obtained from preliminary analysis of the commissioning observations during 2016-2018. We show typical interferometric visibility data, from which we derive the actual beam profile in the east-west direction and the frequency band-pass response. We describe also the calibration process to determine the complex gains for the array elements, either using bright astronomical point sources, or an artificial on site calibrator source, and discuss the instrument response stability, crucial for transit interferometry. Based on this analysis, we find a system temperature of about 90 K, and we also estimate the sensitivity of the array

A high-resolution self-consistent whole sky foreground model

International audienceThe neutral hydrogen 21 cm line is potentially a very powerful probe of the observable universe, and a number of on-going experiments are trying to detect it at cosmological distances. However, the presence of strong foreground radiations such as the galactic synchrotron radiation, galactic free-free emission and extragalactic radio sources make it a very challenging task. For the design of 21 cm experiments and analysis of their data, simulation is an essential tool, and good sky foreground model is needed. With existing data the whole sky maps are available only in low angular resolutions or for limited patches of sky, which is inadequate in the simulation of these new 21 cm experiments. In this paper, we present the method of constructing a high resolution self-consistent sky model at low frequencies, which incorporates both diffuse foreground and point sources. Our diffuse map is constructed by generating physical foreground components including the galactic synchrotron emission and galactic free-free emission. The point source sample is generated using the actual data from the NRAO VLA Sky Survey (NVSS) and the Sydney University Molonglo Sky Survey (SUMSS) where they are available and complete in flux limit, and mock point sources according to statistical distributions. The entire model is made self-consistent by removing the integrated flux of the point sources from the diffuse map so that this part of radiation is not double counted. We show that with the point sources added, a significant angular power is introduced in the mock sky map, which may be important for foreground subtraction simulations. Our sky maps and point source catalogues are available to download

A high-resolution self-consistent whole sky foreground model

International audienceThe neutral hydrogen 21 cm line is potentially a very powerful probe of the observable universe, and a number of on-going experiments are trying to detect it at cosmological distances. However, the presence of strong foreground radiations such as the galactic synchrotron radiation, galactic free-free emission and extragalactic radio sources make it a very challenging task. For the design of 21 cm experiments and analysis of their data, simulation is an essential tool, and good sky foreground model is needed. With existing data the whole sky maps are available only in low angular resolutions or for limited patches of sky, which is inadequate in the simulation of these new 21 cm experiments. In this paper, we present the method of constructing a high resolution self-consistent sky model at low frequencies, which incorporates both diffuse foreground and point sources. Our diffuse map is constructed by generating physical foreground components including the galactic synchrotron emission and galactic free-free emission. The point source sample is generated using the actual data from the NRAO VLA Sky Survey (NVSS) and the Sydney University Molonglo Sky Survey (SUMSS) where they are available and complete in flux limit, and mock point sources according to statistical distributions. The entire model is made self-consistent by removing the integrated flux of the point sources from the diffuse map so that this part of radiation is not double counted. We show that with the point sources added, a significant angular power is introduced in the mock sky map, which may be important for foreground subtraction simulations. Our sky maps and point source catalogues are available to download