Biology subjects

zhang, y.

Publications and source records attributed to zhang, y..

27 records · Page 2Linked to original sources

bioRxiv2022

Deep Learning model accurately classifies metastatic tumors from primary tumors based on mutational signatures

Metastatic propagation is the leading cause of death for most cancers. Prediction and elucidation of metastatic process is crucial for the therapeutic treatment of cancers. Even though somatic mutations have been directly linked to tumorigenesis and metastasis, it is less explored whether the metastatic events can be identified through genomic mutation signatures, a concise representation of the mutational processes. Here, applying mutation signatures as input features calculated from Whole-Exome Sequencing (WES) data of TCGA and other metastatic cohorts, we developed MetaWise, a Deep Neural Network (DNN) model. This model accurately classified metastatic tumors from primary tumors. Signatures of non-coding mutations also have a major impact on the model performance. SHapley Additive exPlanations (SHAP) and Local Surrogate (LIME) analysis into the MetaWise model identified several mutational signatures directly correlated to metastatic spread in cancers, including APOBEC-mutagenesis, UV-induced signatures and DNA damage response deficiency signatures.

cancer biology↗

bioRxiv2022

Single-shot Volumetric Chemical Imaging by Mid- Infrared Photothermal Fourier Light Field Microscopy

Three-dimensional molecular imaging of living organisms and cells plays a significant role in modern biology. Yet, current volumetric imaging modalities are largely fluorescence-based and thus lack chemical content information. Mid-infrared photothermal microscopy as a new chemical imaging technology provides infrared spectroscopic information at sub-micrometer spatial resolution. Here, by harnessing thermosensitive fluorescent dyes to sense the mid-infrared photothermal effect, we demonstrate mid-infrared photothermal Fourier light field (MIP-FLF) microscopy for single-shot volumetric infrared spectroscopic imaging at the speed of 8 volumes per second and sub-micron spatial resolution. Protein contents in bacteria and lipid droplets in living pancreatic cancer cells are visualized. Altered lipid metabolism in drug-resistant pancreatic cancer cells is observed with the MIP-FLF microscope.

biochemistry↗

bioRxiv2022

Thinking like a structural biologist: A pocket-based 3D molecule generative model fueled by electron density

We report for the first time the use of experimental electron density (ED) as training data for the generation of drug-like three-dimensional molecules based on the structure of a target protein pocket. Similar to a structural biologist building molecules based on their ED, our model functions with two main components: a generative adversarial network (GAN) to generate the ligand ED in the input pocket and an ED interpretation module for molecule generation. The model was tested on three targets including kinase (HPK1), protease (Covid19-3CL), and nuclear receptor (VDR), and evaluated with a reference dataset composed of over 8,000 compounds that have their activities reported in the literature. The evaluation examined the chemical validity, chemical space distribution-based diversity, and similarity with reference active compounds concerning the molecular structure and pocket-binding mode. Our model can reproduce classical active compounds and can also generate novel molecules with similar binding modes as active compounds, making it a promising tool for library generation supporting high-throughput virtual screening. Our model is available as an online service to academic users via https://edmg.stonewise.cn/#/create.

bioinformatics↗

bioRxiv2021

Evidence for the Presence of Hyphae and Fruiting Body Calcium Oxalate Crystallites in Schizophyllum commune

Biomineralization is a phenomenon in which organisms form crystals. Studies have shown that many fungi have the ability to biomineralize, it can exhibit calcium oxalate crystals on their hyphae and fruiting body. Schizophyllum commune is a common saprophytic fungus distributed all over the world, but there is little research on its biomineralization. In this paper, S. commune fruiting body from three different provinces of China were collected, and isolation for hyphal cultured to obtain several samples. Utilizing light microscope, FE-SEM, and EDAX, the existence of crystals on the fruiting body and mycelium of each strain was found, and their morphological characteristics and ion content were analyzed. It was ultimately established that biomineralization occurs on S. commune.

biochemistry↗

bioRxiv2021

Effects of carbon, nitrogen, phosphorus, and potassium on flowering and Fruiting of Glycyrrhiza uralensis

AbstractCarbon (C), nitrogen (N), phosphorus (P), and potassium (K) play an important role in flower bud differentiation and seed-filling; however, the effects of these elements on the flowering and fruiting of Glycyrrhiza uralensis Fisch. are not known. In this study, we evaluated the differences in the C, N, P, and K levels between the fruiting and nonfruiting plants of G. uralensis at different growth stages. The correlations between the elements C, N, P, and K and the flower and fruit falling rates, rate of empty seeds, rate of shrunken grains, and thousand kernel weight (TKW) were also determined. The results show that the P and K levels and C:N, P:N, and K:N ratios of flowering plants are significantly higher than those of nonflowering plants; N level of flowering plants is significantly lower than that of nonflowering plants at the flower bud differentiation stage. The number of inflorescences was positively correlated with C and K levels and C:N and K:N ratios. A low level of C, P, and K and high level of N in flowering and pod setting stage may lead to the flower and fruit drop of G. uralensis. The K level is significantly negatively correlated with the rates of empty and shrunken seeds. The N level is significantly positively correlated with TKW. Thus, high levels of C, P, and K might be beneficial to flower bud differentiation, while higher levels of N is not beneficial to the flower bud formation of G. uralensis. Higher levels of N and K at the filling stage were beneficial to the seed setting and seed-filling of G. uralensis. HighlightHigh levels of C, P, and K might be beneficial to flower bud differentiation, while higher levels of N is not beneficial to the flower bud formation of G. uralensis. Higher levels of N and K at the filling stage were beneficial to the seed setting and seed-filling of G. uralensis.

plant biology↗

bioRxiv2020

The Profiling of Bisecting N-acetylglucosamine (GlcNAc) Modification in Human Amniotic Membrane by Glycomic and Glycoproteomic Analyses

It is acknowledged that the bisecting N-acetylglucosamine (GlcNAc) structure, a GlcNAc linked to the core {beta}-mannose residue via a {beta}1,4 linkage, represents a special type of N-glycosylated modification and has been reported to be involved in various biological processes, such as cell adhesion and fetal development. Clark et al. has found that the majority of N-glycans in human trophoblasts bearing a bisecting GlcNAc. This type of glycan has been reported to help trophoblasts get resistant to natural killer (NK) cell-mediated cytotoxicity, and this would provide a possible explanation for the question how could the mother nourish a fetus within herself without rejection. Herein, we hypothesized that human amniotic membrane which is the last barrier for the fetus may also express bisecting type glycans to protect the fetus. To test this hypothesis, glycomic analysis of human amniotic membrane was performed, and the bisecting N-glycans with high abundance were detected. In addition, we re-analyzed our proteomic data with high fractionation and amino acid sequence coverage from human amniotic membrane, which had been released for the exploration of human missing proteins. The presence of bisecting GlcNAc peptides was revealed and confirmed. A total of 41 glycoproteins with 43 glycopeptides were found to possess a bisecting GlcNAc, 25 of which are for the first time to be reported to have this type of modification. These results provide the profiling of bisecting GlcNAc modification in human amniotic membrane and benefit to the function studies of glycoproteins with bisecting GlcNAc modification and the function studies in immune suppression of human placenta. The mass spectrometry placenta data are available via ProteomeXchange (PXD010630).

cell biology↗

bioRxiv2020

Functional Interrogation of HOXA9 Regulome in MLLr Leukemia via Reporter-based CRISPR/Cas9 screen

Aberrant HOXA9 expression is a hallmark of most aggressive acute leukemias, including human acute myeloid leukemia (AML) and subtypes of acute lymphoblastic leukemia (ALL). HOXA9 overexpression not only predicts poor diagnosis and outcome but also plays a critical role in leukemia transformation and maintenance. However, our current understanding of HOXA9 regulation in leukemia is limited, hindering development of therapeutic strategies to treat HOXA9-driven leukemia. To mitigate these challenges, we generated the first HOXA9-mCherry knock-in reporter in an MLL-rearranged (MLLr) B-ALL cell line to dissect HOXA9 regulation. By utilizing the reporter and CRISPR/Cas9 mediated screens, we identified transcription factors controlling HOXA9 expression, including a novel regulator, USF2 and its homolog USF1. USF1/USF2 depletion significantly down-regulated HOXA9 expression and impaired MLLr leukemia cell proliferation. Ectopic expression of HOXA9-MEIS1 fusion protein rescued the impaired leukemia cell proliferation upon USF2 loss. Cut&Run analysis revealed the direct occupancy of USF2 onto HOXA9 promoter in MLLr leukemia cells. Collectively, the HOXA9 reporter facilitated the functional interrogation of the HOXA9 regulome and has advanced our understanding of the molecular regulation network in HOXA9-driven leukemia.

cancer biology↗

bioRxiv2020

Selective Germline Genome Edited Pig Meninges Grafts for the Abdominal Wall Closure in Damage Control Surgery

Reconstruction of abdominal wall defects is still a big challenge in surgery, especially where there is insufficient fascia muscular or excessive tension of the defects in emergency and life-threatening scenarios. Indeed, the concept of damage control surgery has been advanced in the management of both traumatic and nontraumatic surgical settings. The strategy requires abridged surgery and quick back to intensive care units (ICU) for aggressive resuscitation. In the damage control laparotomy, patients are left with open abdomen or provisional closure of the abdomen with a planned return to the operating room for definitive surgery. So far, various techniques have been utilized to achieve early temporary abdominal closure, but there is no clear consensus on the ideal method or material for abdominal wall reconstruction. We recently successfully created the selective germline genome-edited pig (SGGEP) and here we aimed to explore the feasibility of in vivo reconstruction of the abdominal wall in a rabbit model with SGGEP meninges grafts (SGGEP-MGs). Our result showed that the SGGEP-MGs could restore the integrity of the defect very well. After 7 weeks of engraftment, there was no sign of herniation observed, the grafts were re-vascularized, and the defects were well repaired. Histologically, the boundary between the graft and the host was very well integrated and there was no strong inflammatory response. Therefore, this kind of closure could help restore the fluid and electrolyte balance and to dampen systemic inflammatory response in damge control surgery while ADM graft failed to establish re-vascularization as the same as the SGGEP-MG. It is concluded that the meninges of SGGEP could serve as a high-quality alternative for restoring the integrity of the abdominal wall, especially for damage control surgery.

synthetic biology↗

bioRxiv2019

An atlas of infiltrated B-lymphocytes in breast cancer revealed by paired single-cell RNA-sequencing and antigen receptor profiling

While it has been well-recognized that T-cell mediated adaptive cellular immunity plays important roles in cancer immune response and tumor control, the roles of B lymphocytes in tumor development and therapy have only been proposed until recently, and are still mostly controversial. To gain mechanistic insights into the origin and dynamics of tumor infiltrated immune cells, especially B lymphocytes, we combine single-cell RNA-sequencing and antigen receptor lineage analysis to characterize a large number of triple-negative breast cancer (TNBC) infiltrated immune cells and present a comprehensive atlas of infiltrated B-lymphocytes in TNBC, the most aggressive breast cancer subtype. We demonstrate that TNBC infiltrated B cells showed more mature and memory B cell characteristics, as well as high clonality and extensive IgH class switching recombination and somatic hypermutations. The B cell signatures based on single-cell RNA-seq results are significantly associated with improved survival for TNBC patients and provide better prognostication than classic single B cell markers (CD19 or CD20). Further dissection of the mechanisms regulating the functions and dynamic distribution of tumor infiltrated B cell populations will provide new clues for tumor immunotherapy.

immunology↗