bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exome reanalysis and proteomic profiling identified TRIP4 as a novel cause of cerebellar hypoplasia and spinal muscular atrophy (PCH1)
Authors: Töpf Ana , Pyle Angela , Griffin Helen , Matalonga Leslie , Schon Katherine ,   Solve-RD SNV-indel working group, Cohen Enzo , Cuesta Isabel , Danis Daniel , Denommé-Pichon Anne-Sophie , Duffourd Yannis , Gilissen Christian , Johari Mridul , Laurie Steven , Li Shuang , Nelson Isabelle , Paramonov Ida , Peters Sophia , Prasanth Sivakumar , Robinson Peter , Sablauskas Karolis , Savarese Marco , Steyaert Wouter , van der Velde Joeri K. , Vitobello Antonio ,   Solve-RD DITF-euroNMD, Baets Jonathan , Beijer Danique , Bonne Gisèle , Cossins Judith , Evangelista Teresinha , Ferlini Alessandra , Hackman Peter , Hanna Michael G. , Houlden Henry , Lau Jarred , Lochmüller Hanns , Macken William L. , Musacchia Francesco , Nascimento Andres , Natera-de Benito Daniel , Nigro Vincenzo , Piluso Giulio , Pini Veronica , Pitceathly Robert D. S. , Polavarapu Kiran , Cruz Pedro M. Rodriguez , Sarkozy Anna , Selvatici Rita , Thompson Rachel , Torella Annalaura , Udd Bjarne , Van de Vondel Liedewei , Vandrovcova Jana , Zaharieva Irina , Sickmann Albert , Schara–Schmidt Ulrike , Hentschel Andreas , Chinnery Patrick F. , Kölbel Heike , Roos Andreas , Horvath Rita 
Published: June 2021

AbstractTRIP4 is one of the subunits of the transcriptional coregulator ASC-1, a ribonucleoprotein complex that participates in transcriptional coactivation and RNA processing events. Recessive variants in the TRIP4 gene have been associated with spinal muscular atrophy with bone fractures as well as a severe form of congenital muscular dystrophy. Here we present the diagnostic journey of a patient with cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures. Initial exome sequencing analysis revealed no candidate variants. Reanalysis of the exome data by inclusion in the Solve-RD project resulted in the identification of a homozygous stop-gain variant in the TRIP4 gene, previously reported as disease-causing. This highlights the importance of analysis reiteration and improved and updated bioinformatic pipelines. Proteomic profile of the patient’s fibroblasts showed altered RNA-processing and impaired exosome activity supporting the pathogenicity of the detected variant. In addition, we identified a novel genetic form of PCH1, further strengthening the link of this characteristic phenotype with altered RNA metabolism.
A high-quality genome assembly of Morinda officinalis, a famous native southern herb in the Lingnan region of southern China
Authors: Wang Jihua , Xu Shiqiang , Mei Yu , Cai Shike , Gu Yan , Sun Minyang , Liang Zhan , Xiao Yong , Zhang Muqing , Yang Shaohai 
Published: June 2021

Abstract
Morinda officinalis is a well-known medicinal and edible plant that is widely cultivated in the Lingnan region of southern China. Its dried roots (called bajitian in traditional Chinese medicine) are broadly used to treat various diseases, such as impotence and rheumatism. Here, we report a high-quality chromosome-scale genome assembly of M. officinalis using Nanopore single-molecule sequencing and Hi-C technology. The assembled genome size was 484.85 Mb with a scaffold N50 of 40.97 Mb, and 90.77% of the assembled sequences were anchored on eleven pseudochromosomes. The genome includes 27,698 protein-coding genes, and most of the assemblies are repetitive sequences. Genome evolution analysis revealed that M. officinalis underwent core eudicot γ genome triplication events but no recent whole-genome duplication (WGD). Likewise, comparative genomic analysis showed no large-scale structural variation after species divergence between M. officinalis and Coffea canephora. Moreover, gene family analysis indicated that gene families associated with plant–pathogen interactions and sugar metabolism were significantly expanded in M. officinalis. Furthermore, we identified many candidate genes involved in the biosynthesis of major active components such as anthraquinones, iridoids and polysaccharides. In addition, we also found that the DHQS, GGPPS, TPS-Clin, TPS04, sacA, and UGDH gene families—which include the critical genes for active component biosynthesis—were expanded in M. officinalis. This study provides a valuable resource for understanding M. officinalis genome evolution and active component biosynthesis. This work will facilitate genetic improvement and molecular breeding of this commercially important plant.
Easy domain adaptation method for filling the species gap in deep learning-based fruit detection
Authors: Zhang Wenli , Chen Kaizhen , Wang Jiaqi , Shi Yun , Guo Wei 
Published: June 2021

AbstractFruit detection and counting are essential tasks for horticulture research. With computer vision technology development, fruit detection techniques based on deep learning have been widely used in modern orchards. However, most deep learning-based fruit detection models are generated based on fully supervised approaches, which means a model trained with one domain species may not be transferred to another. There is always a need to recreate and label the relevant training dataset, but such a procedure is time-consuming and labor-intensive. This paper proposed a domain adaptation method that can transfer an existing model trained from one domain to a new domain without extra manual labeling. The method includes three main steps: transform the source fruit image (with labeled information) into the target fruit image (without labeled information) through the CycleGAN network; Automatically label the target fruit image by a pseudo-label process; Improve the labeling accuracy by a pseudo-label self-learning approach. Use a labeled orange image dataset as the source domain, unlabeled apple and tomato image dataset as the target domain, the performance of the proposed method from the perspective of fruit detection has been evaluated. Without manual labeling for target domain image, the mean average precision reached 87.5% for apple detection and 76.9% for tomato detection, which shows that the proposed method can potentially fill the species gap in deep learning-based fruit detection.
The role of the MAP kinase−kinase protein StMKK1 in potato immunity to different pathogens
Authors: Chen Xiaokang , Wang Wenbin , Cai Pingping , Wang Ziwei , Li Tingting , Du Yu 
Published: June 2021

AbstractMitogen-activated protein kinase (MAPK) cascades play important roles in plant immunity. Previously, we reported that the potato StMKK1 protein negatively regulates Nicotiana benthamiana resistance to Phytophthora infestans. However, the functions of StMKK1 in potato immunity are unknown. To investigate the roles of StMKK1 in potato resistance to different pathogens, such as the potato late-blight pathogen P. infestans, the bacterial wilt pathogen Ralstonia solanacearum, and the gray-mold fungal pathogen Botrytis cinerea, we generated StMKK1 transgenic lines and investigated the response of potato transformants to destructive oomycete, bacterial, and fungal pathogens. The results showed that overexpression and silencing of StMKK1 do not alter plant growth and development. Interestingly, we found that StMKK1 negatively regulated potato resistance to the hemibiotrophic/biotrophic pathogens P. infestans and R. solanacearum, while it positively regulated potato resistance to the necrotrophic pathogen B. cinerea. Further investigation showed that overexpression of StMKK1 suppressed potato pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and salicylic acid (SA)-related responses, while silencing of StMKK1 enhanced PTI and SA-related immune responses. Taken together, our results showed that StMKK1 plays dual roles in potato defense against different plant pathogens via negative regulation of PTI and SA-related signaling pathways.
The chromosome-level reference genome of Coptis chinensis provides insights into genomic evolution and berberine biosynthesis
Authors: Chen Da-xia , Pan Yuan , Wang Yu , Cui Yan-Ze , Zhang Ying-Jun , Mo Rang-yu , Wu Xiao-li , Tan Jun , Zhang Jian , Guo Lian-an , Zhao Xiao , Jiang Wenkai , Sun Tian-lin , Hu Xiao-Di , Li Long-yun 
Published: June 2021

AbstractCoptis chinensis Franch, a perennial herb, is mainly distributed in southeastern China. The rhizome of C. chinensis has been used as a traditional medicine for more than 2000 years in China and many other Asian countries. The pharmacological activities of C. chinensis have been validated by research. Here, we present a de novo high-quality genome of C. chinensis with a chromosome-level genome of ~958.20 Mb, a contig N50 of 1.58 Mb, and a scaffold N50 of 4.53 Mb. We found that the relatively large genome size of C. chinensis was caused by the amplification of long terminal repeat (LTR) retrotransposons. In addition, a whole-genome duplication event in ancestral Ranunculales was discovered. Comparative genomic analysis revealed that the tyrosine decarboxylase (TYDC) and (S)-norcoclaurine synthase (NCS) genes were expanded and that the aspartate aminotransferase gene (ASP5) was positively selected in the berberine metabolic pathway. Expression level and HPLC analyses showed that the berberine content was highest in the roots of C. chinensis in the third and fourth years. The chromosome-level reference genome of C. chinensis provides important genomic data for molecular-assisted breeding and active ingredient biosynthesis.
Comprehensive analysis of SSRs and database construction using all complete gene-coding sequences in major horticultural and representative plants
Authors: Song Xiaoming , Yang Qihang , Bai Yun , Gong Ke , Wu Tong , Yu Tong , Pei Qiaoying , Duan Weike , Huang Zhinan , Wang Zhiyuan , Liu Zhuo , Kang Xi , Zhao Wei , Ma Xiao 
Published: June 2021

AbstractSimple sequence repeats (SSRs) are one of the most important genetic markers and widely exist in most species. Here, we identified 249,822 SSRs from 3,951,919 genes in 112 plants. Then, we conducted a comprehensive analysis of these SSRs and constructed a plant SSR database (PSSRD). Interestingly, more SSRs were found in lower plants than in higher plants, showing that lower plants needed to adapt to early extreme environments. Four specific enriched functional terms in the lower plantChlamydomonas reinhardtiiwere detected when it was compared with seven other higher plants. In addition, Guanylate_cyc existed in more genes of lower plants than of higher plants. In our PSSRD, we constructed an interactive plotting function in the chart interface, and users can easily view the detailed information of SSRs. All SSR information, including sequences, primers, and annotations, can be downloaded from our database. Moreover, we developed Web SSR Finder and Batch SSR Finder tools, which can be easily used for identifying SSRs. Our database was developed using PHP, HTML, JavaScript, and MySQL, which are freely available athttp://www.pssrd.info/. We conducted an analysis of the Myb gene families and flowering genes as two applications of the PSSRD. Further analysis indicated that whole-genome duplication and whole-genome triplication played a major role in the expansion of the Myb gene families. These SSR markers in our database will greatly facilitate comparative genomics and functional genomics studies in the future.
Transcriptome and physiological analyses provide insights into the leaf epicuticular wax accumulation mechanism in yellowhorn
Authors: Zhao Yang , Liu Xiaojuan , Wang Mengke , Bi Quanxin , Cui Yifan , Wang Libing 
Published: June 2021

AbstractPlantations and production of yellowhorn, one of the most important woody oil and urban greening trees widely cultivated in northern China, have gradually become limited by drought stress. The epicuticular wax layer plays a key role in the protection of yellowhorn trees from drought and other stresses. However, there is no research on the mechanism of wax loading in yellowhorn trees. In this study, we investigated the anatomical and physiological characteristics of leaves from different germplasm resources and different parts of the same tree and compared their cuticle properties. In addition, the different expression patterns of genes involved in wax accumulation were analyzed, and a coexpression network was built based on transcriptome sequencing data. Morphological and physiological comparisons found that the sun leaves from the outer part of the crown had thicker epicuticular wax, which altered the permeability and improved the drought resistance of leaves, than did shade leaves. Based on transcriptome data, a total of 3008 and 1324 differentially expressed genes (DEGs) were identified between the sun leaves and shade leaves in glossy- and non-glossy-type germplasm resources, respectively. We identified 138 DEGs involved in wax biosynthesis and transport, including structural genes (such as LACS8, ECH1, and ns-LTP) and transcription factors (such as MYB, WRKY, and bHLH transcription factor family proteins). The coexpression network showed a strong correlation between these DEGs. The differences in gene expression patterns between G- and NG-type germplasm resources under different light conditions were very clear. These results not only provide a theoretical basis for screening and developing drought-resistant yellowhorn germplasm resources but also provide a data platform to reveal the wax accumulation process of yellowhorn leaves.
The chromosome-level Stevia genome provides insights into steviol glycoside biosynthesis
Authors: Xu Xiaoyang , Yuan Haiyan , Yu Xiaqing , Huang Suzhen , Sun Yuming , Zhang Ting , Liu Qingquan , Tong Haiying , Zhang Yongxia , Wang Yinjie , Liu Chunxiao , Wu Lei , Hou Menglan , Yang Yongheng 
Published: June 2021

AbstractStevia (Stevia rebaudianaBertoni) is well known for its very sweet steviol glycosides (SGs) consisting of a common tetracyclic diterpenoid steviol backbone and a variable glycone. Steviol glycosides are 150–300 times sweeter than sucrose and are used as natural zero-calorie sweeteners. However, the most promising compounds are biosynthesized in small amounts. Based on Illumina, PacBio, and Hi-C sequencing, we constructed a chromosome-level assembly of Stevia covering 1416 Mb with a contig N50 value of 616.85 kb and a scaffold N50 value of 106.55 Mb. More than four-fifths of the Stevia genome consisted of repetitive elements. We annotated 44,143 high-confidence protein-coding genes in the high-quality genome. Genome evolution analysis suggested that Stevia and sunflower diverged ~29.4 million years ago (Mya), shortly after the whole-genome duplication (WGD) event (WGD-2, ~32.1 Mya) that occurred in their common ancestor. Comparative genomic analysis revealed that the expanded genes in Stevia were mainly enriched for biosynthesis of specialized metabolites, especially biosynthesis of terpenoid backbones, and for further oxidation and glycosylation of these compounds. We further identified all candidate genes involved in SG biosynthesis. Collectively, our current findings on the Stevia reference genome will be very helpful for dissecting the evolutionary history of Stevia and for discovering novel genes contributing to SG biosynthesis and other important agronomic traits in future breeding programs.
Identification of the PmWEEP locus controlling weeping traits in Prunus mume through an integrated genome-wide association study and quantitative trait locus mapping
Authors: Zhuo Xiaokang , Zheng Tangchun , Li Suzhen , Zhang Zhiyong , Zhang Man , Zhang Yichi , Ahmad Sagheer , Sun Lidan , Wang Jia , Cheng Tangren , Zhang Qixiang 
Published: June 2021

AbstractWeepingPrunus mume(mei) has long been cultivated in East Asia for its specific ornamental value. However, little is known about the regulatory mechanism of the weeping trait in mei, which limits molecular breeding for the improvement of weeping-type cultivars. Here, we quantified the weeping trait in mei using nested phenotyping of 214 accessions and 342 F1hybrids. Two major associated loci were identified from the genome-wide association study (GWAS), which was conducted using 3,014,409 single nucleotide polymorphisms (SNPs) derived from resequencing, and 8 QTLs and 55 epistatic loci were identified from QTL mapping using 7,545 specific lengths amplified fragment (SLAF) markers. Notably, an overlappingPmWEEPmajor QTL was fine mapped within a 0.29 Mb region on chromosome 7 (Pa7), and a core SNP locus closely associated with the weeping trait was screened and validated. Furthermore, a total of 22 genes in thePmWEEPQTL region were expressed in weeping or upright mei based on RNA-seq analysis. Among them, only a novel gene (Pm024213) containing a thioredoxin (Trx) domain was found to be close to the core SNP and specifically expressed in buds and branches of weeping mei. Co-expression analysis ofPm024213showed that most of the related genes were involved in auxin and lignin biosynthesis. These findings provide insights into the regulatory mechanism of the weeping trait and effective molecular markers for molecular-assisted breeding inPrunus mume.
Abnormal brain cholesterol homeostasis in Alzheimer’s disease—a targeted metabolomic and transcriptomic study
Authors: Varma Vijay R. , Büşra Lüleci H. , Oommen Anup M. , Varma Sudhir , Blackshear Chad T. , Griswold Michael E. , An Yang , Roberts Jackson A. , O’Brien Richard , Pletnikova Olga , Troncoso Juan C. , Bennett David A. , Çakır Tunahan , Legido-Quigley Cristina , Thambisetty Madhav 
Published: June 2021

AbstractThe role of brain cholesterol metabolism in Alzheimer’s disease (AD) remains unclear. Peripheral and brain cholesterol levels are largely independent due to the impermeability of the blood brain barrier (BBB), highlighting the importance of studying the role of brain cholesterol homeostasis in AD. We first tested whether metabolite markers of brain cholesterol biosynthesis and catabolism were altered in AD and associated with AD pathology using linear mixed-effects models in two brain autopsy samples from the Baltimore Longitudinal Study of Aging (BLSA) and the Religious Orders Study (ROS). We next tested whether genetic regulators of brain cholesterol biosynthesis and catabolism were altered in AD using the ANOVA test in publicly available brain tissue transcriptomic datasets. Finally, using regional brain transcriptomic data, we performed genome-scale metabolic network modeling to assess alterations in cholesterol biosynthesis and catabolism reactions in AD. We show that AD is associated with pervasive abnormalities in cholesterol biosynthesis and catabolism. Using transcriptomic data from Parkinson’s disease (PD) brain tissue samples, we found that gene expression alterations identified in AD were not observed in PD, suggesting that these changes may be specific to AD. Our results suggest that reduced de novo cholesterol biosynthesis may occur in response to impaired enzymatic cholesterol catabolism and efflux to maintain brain cholesterol levels in AD. This is accompanied by the accumulation of nonenzymatically generated cytotoxic oxysterols. Our results set the stage for experimental studies to address whether abnormalities in cholesterol metabolism are plausible therapeutic targets in AD.
Modeling transcriptomic age using knowledge-primed artificial neural networks
Authors: Holzscheck Nicholas , Falckenhayn Cassandra , Söhle Jörn , Kristof Boris , Siegner Ralf , Werner André , Schössow Janka , Jürgens Clemens , Völzke Henry , Wenck Horst , Winnefeld Marc , Grönniger Elke , Kaderali Lars 
Published: June 2021

AbstractThe development of ‘age clocks’, machine learning models predicting age from biological data, has been a major milestone in the search for reliable markers of biological age and has since become an invaluable tool in aging research. However, beyond their unquestionable utility, current clocks offer little insight into the molecular biological processes driving aging, and their inner workings often remain non-transparent. Here we propose a new type of age clock, one that couples predictivity with interpretability of the underlying biology, achieved through the incorporation of prior knowledge into the model design. The clock, an artificial neural network constructed according to well-described biological pathways, allows the prediction of age from gene expression data of skin tissue with high accuracy, while at the same time capturing and revealing aging states of the pathways driving the prediction. The model recapitulates known associations of aging gene knockdowns in simulation experiments and demonstrates its utility in deciphering the main pathways by which accelerated aging conditions such as Hutchinson–Gilford progeria syndrome, as well as pro-longevity interventions like caloric restriction, exert their effects.
Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer
Authors: Luo Rui , Chong Weelic , Wei Qiang , Zhang Zhenchao , Wang Chun , Ye Zhong , Abu-Khalaf Maysa M. , Silver Daniel P. , Stapp Robert T. , Jiang Wei , Myers Ronald E. , Li Bingshan , Cristofanilli Massimo , Yang Hushan 
Published: June 2021

AbstractInflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Although it is a rare subtype, IBC is responsible for roughly 10% of breast cancer deaths. In order to obtain a better understanding of the genomic landscape and intratumor heterogeneity (ITH) in IBC, we conducted whole-exome sequencing of 16 tissue samples (12 tumor and four normal samples) from six hormone-receptor-positive IBC patients, analyzed somatic mutations and copy number aberrations, and inferred subclonal structures to demonstrate ITH. Our results showed that KMT2C was the most frequently mutated gene (42%, 5/12 samples), followed by HECTD1, LAMA3, FLG2, UGT2B4, STK33, BRCA2, ACP4, PIK3CA, and DNAH8 (all nine genes tied at 33% frequency, 4/12 samples). Our data indicated that PTEN and FBXW7 mutations may be considered driver gene mutations for IBC. We identified various subclonal structures and different levels of ITH between IBC patients, and mutations in the genes EIF4G3, IL12RB2, and PDE4B may potentially generate ITH in IBC.
Risk of primary lung cancer after adjuvant radiotherapy in breast cancer—a large population-based study
Authors: Wennstig Anna-Karin , Wadsten Charlotta , Garmo Hans , Johansson Mikael , Fredriksson Irma , Blomqvist Carl , Holmberg Lars , Nilsson Greger , Sund Malin 
Published: June 2021

AbstractAdjuvant radiotherapy (RT) for breast cancer (BC) has been associated with an increased risk of later radiation-induced lung cancer (LC). We examined the risk of primary LC in a population-based cohort of 52300 women treated for BC during 1992 to 2012, and 253796 age-matched women without BC. Cumulative incidence of LC was calculated by the Kaplan–Meier method, and the risk of LC after BC treatment was estimated by Cox proportional hazards regression analyses. Women with BC receiving RT had a higher cumulative incidence of LC compared to women with BC not receiving RT and women without BC. This became apparent 5 years after RT and increased with longer follow-up. Women with BC receiving RT had a Hazard ratio of 1.59 (95% confidence interval 1.37–1.84) for LC compared to women without BC. RT techniques that lower the incidental lung doses, e.g breathing adaption techniques, may lower this risk.