Genome Browser Research Articles

Generation of an isoform-level transcriptome atlas of macrophage activation

RNA-seq is routinely used to measure gene expression changes in response to cell perturbation. Genes upregulated or downregulated following some perturbation are designated as genes of interest, and their most expressed isoform(s) would then be selected for follow-up experimentation. However, because of its need to fragment RNA molecules, RNA-seq is limited in its ability to capture gene isoforms and their expression patterns. This lack of isoform-specific data means that isoforms would be selected based on annotation databases that are incomplete, not tissue specific, or do not provide key information on expression levels. As a result, minority or nonexistent isoforms might be selected for follow-up, leading to loss in valuable resources and time. There is therefore a great need to comprehensively identify gene isoforms along with their corresponding levels of expression. Using the long-read nanopore-based R2C2 method, which does not fragment RNA molecules, we generated an Isoform-level transcriptome Atlas of Macrophage Activation that identifies full-length isoforms in primary human monocyte-derived macrophages. Macrophages are critical innate immune cells important for recognizing pathogens through binding of pathogen-associated molecular patterns to toll-like receptors, culminating in the initiation of host defense pathways. We characterized isoforms for most moderately-to-highly expressed genes in resting and toll-like receptor–activated monocyte-derived macrophages, identified isoforms differentially expressed between conditions, and validated these isoforms by RT-qPCR. We compiled these data into a user-friendly data portal within the UCSC Genome Browser (https://genome.ucsc.edu/s/vollmers/IAMA). Our atlas represents a valuable resource for innate immune research, providing unprecedented isoform information for primary human macrophages.

Sex-Associated Gene Expression Alterations Correlate With Esophageal Cancer Survival.

OBJECTIVES:Esophageal cancer (EC) is a significant cause of cancer death with 5-year survival of 10%–15% and males more frequently affected. Genetic evaluation for loci highlighting risk has been performed, but survival data are limited. The Cancer Genome Atlas (TCGA) data sets allow for potential prognostic marker assessment in large patient cohorts. The study aimed to use the TCGA EC data set to assess whether survival varies by sex and explore genetic alterations that may explain variation observed.METHODS:TCGA clinical/RNA-seq data sets (n = 185, 158 males/27 females) were downloaded from the cancer genome browser. Data analysis/figure preparation was performed in R and GraphPad Prism 7. Survival analysis was performed using the survival package. Text mining of PubMed was performed using the tm, RISmed, and wordcloud packages. Pathway analysis was performed using the Reactome database.RESULTS:In EC, male sex/high tumor grade reduced overall survival (hazard ratio = 2.27 [0.99–5.24] for M vs F and 2.49 [0.89–6.92] for low vs high grade, respectively) and recurrence-free survival (hazard ratio = 4.09 [0.98–17.03] for M vs F and 3.36 [0.81–14.01] for low vs high grade, respectively). To investigate the genetic basis for sex-based survival differences in EC, corresponding gene expression data were analyzed. Sixty-nine genes were dysregulated at the P < 0.01 level by the Wilcox test, 33% were X-chromosome genes, and 7% were Y-chromosome genes.DISCUSSION:Female sex potentially confers an EC survival advantage. Importantly, we demonstrate a genetic/epigenetic basis for these survival differences that are independent of lifestyle-associated risk factors overrepresented in males. Further research may lead to novel concepts in treating/measuring EC aggressiveness by sex.

Inter-3' ends CpG islands are enriched in human chromosome 19p13.3 region

Metabolic disease is a pandemic in modern times. However, understanding of the genomic basis associated with metabolism remains to be further elucidated. CpG islands are the genomic regions enriched in cytosine nucleotide (C) and guanine nucleotide (G), mostly located at promoters and contain the 5' end of the gene transcript. In this study, we utilize the UCSC Genome Browser to map the genomic locations and extract the CpG island tracks that are associated with the genes encoding functions in cell metabolism or metabolic disease. We identified a new genomic signature, namely inter-3' end CpG island (ITCI), associated with the genes encoding major metabolic regulators or enzymes in the human chromosome 19p13.3 region. In this region, the gene encoding a major metabolic regulator, CREB3L3, possesses a conserved CpG island in its 3' end. This unique ITCI genomic signature has been found in nine pairs of genes in the human chromosome 19p13.3 region. Many of these genes are associated with metabolism. In conclusion, we discovered a new type of genomic signature, ITCI, which is featured by a dozen of metabolic genes possessing conserved CpG islands in their 3' ends, in a specific human chromosome. Identification of ITCI signature and decoding of the ITCI-associated associated metabolic genes provide important insights into the genomic basis of metabolism or metabolic disease.

Identification of Biomarkers Based on Bioinformatics Analysis: The Expression of Ubiquitin-Conjugating Enzyme E2T (UBE2T) in the Carcinogenesis and Progression of Hepatocellular Carcinoma.

BackgroundThe purpose of this study was to screen and identify key genes in the occurrence and development of hepatocellular carcinoma (HCC) based on bioinformatics analysis.Material/MethodsThree Gene Expression Omnibus (GEO) series (GSE) – GSE121248, GSE87630, and GSE84598 – were downloaded from the GEO database. GEO2R was used to screen different genes and a Venn diagram was drawn to screen coexpressed differentially expressed genes (DEGs). Coexpressed DEGs were obtained by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, a protein-protein interaction network diagram was produced by Cytoscape, and module genes were calculated by the Molecular Complex Detection Cytoscape plug-in. Finally, overall survival, progression-free survival, and relapse-free survival analysis of the key genes selected were performed using the online Kaplan-Meier plotter. For the target genes, the online network UCSC Cancer Genome Browser was used to analyze the gene expression profiles of the grade and vascular invasion of HCC.ResultsA total of 296 coexpressed DEGs were obtained from the 3 GSEs and 12 key genes were obtained from the modular analysis. Survival analysis showed that the upregulated genes UBE2T and FBLN5 were involved in the poor prognosis of HCC. Furthermore, the expression of UBE2T was significantly related to the grade and vascular invasion of HCC.ConclusionsThe expression of the UBE2T gene was significantly upregulated in HCC tissue compared to in normal liver tissue. UBE2T may be a new marker for the diagnosis and subsequent therapy of HCC.

SeMPI 2.0-A Web Server for PKS and NRPS Predictions Combined with Metabolite Screening in Natural Product Databases.

Microorganisms produce secondary metabolites with a remarkable range of bioactive properties. The constantly increasing amount of published genomic data provides the opportunity for efficient identification of biosynthetic gene clusters by genome mining. On the other hand, for many natural products with resolved structures, the encoding biosynthetic gene clusters have not been identified yet. Of those secondary metabolites, the scaffolds of nonribosomal peptides and polyketides (type I modular) can be predicted due to their building block-like assembly. SeMPI v2 provides a comprehensive prediction pipeline, which includes the screening of the scaffold in publicly available natural compound databases. The screening algorithm was designed to detect homologous structures even for partial, incomplete clusters. The pipeline allows linking of gene clusters to known natural products and therefore also provides a metric to estimate the novelty of the cluster if a matching scaffold cannot be found. Whereas currently available tools attempt to provide comprehensive information about a wide range of gene clusters, SeMPI v2 aims to focus on precise predictions. Therefore, the cluster detection algorithm, including building block generation and domain substrate prediction, was thoroughly refined and benchmarked, to provide high-quality scaffold predictions. In a benchmark based on 559 gene clusters, SeMPI v2 achieved comparable or better results than antiSMASH v5. Additionally, the SeMPI v2 web server provides features that can help to further investigate a submitted gene cluster, such as the incorporation of a genome browser, and the possibility to modify a predicted scaffold in a workbench before the database screening.

Comparison of the single nucleotide polymorphisms and expression of FSHβ and LHβ genes between prolific and non-prolific goat breeds of Kerala

Attappady Black and Malabari breeds of goats are native to Kerala, a southern state of India. Attappady Black is a low prolific breed whereas Malabari breed is highly prolific. Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) are the gonadotropins which are considered to be the central hormones controlling prolificacy. The present study aimed to detect presence of SNPs in exonic regions of FSHβ and LHβ and the expression of these gonadotropins in both these breeds. Blood samples were collected from ten does five each from Attappady Black and Malabari goats and the genomic DNA was extracted. Multiple primers were designed based on Ensembl Genome Browser sequences to cover the entire exonic regions of both the genes for SNP detection. Pooled PCR products of FSHβ and LHβ separately from the two breeds were sequenced. Nucleotide sequencing showed synonymous single nucleotide polymorphism T → C, in FSHβ coding sequence, at position 413 (as per FSHβ ENSCHIG00000022859), in both Attappady Black and Malabari goats. Numerous other SNPs both novel and reported were detected in the non-coding regions of FSHβ. In LHβ of Attappady Black goat, an SNP was found at exonic position 455 (G → A) as per LHβ ENSCHIT00000012663.1. This transition resulted in replacement of amino acid arginine (R) with glutamine (Q). Upon individual sequencing of ten each of single birth and multiple birth Attappady Black goat samples, three animals with single birth and five animals with multiple birth showed G → A change in the LHβ transcript at position 455. Pituitary samples were collected from 6 animals each from both the breeds and expressions of both the genes were quantified using qRT-PCR technique. There was no significant difference in pituitary FSHβ expression between breeds. However, there was a significant difference (P < 0.01) in LHβ expression between the two breeds with an increase in expression of 2.61 folds in Attappady Black breed. This study forewarn a main role for LH in the genetic network controlling prolificacy in these goat breeds and this necessitates further investigation with larger sample size and also in other goat breeds.

MOSGA: Modular Open-Source Genome Annotator.

The generation of high-quality assemblies, even for large eukaryotic genomes, has become a routine task for many biologists thanks to recent advances in sequencing technologies. However, the annotation of these assemblies-a crucial step toward unlocking the biology of the organism of interest-has remained a complex challenge that often requires advanced bioinformatics expertise. Here, we present MOSGA (Modular Open-Source Genome Annotator), a genome annotation framework for eukaryotic genomes with a user-friendly web-interface that generates and integrates annotations from various tools. The aggregated results can be analyzed with a fully integrated genome browser and are provided in a format ready for submission to NCBI. MOSGA is built on a portable, customizable and easily extendible Snakemake backend, and thus, can be tailored to a wide range of users and projects. We provide MOSGA as a web service at https://mosga.mathematik.uni-marburg.de and as a docker container at registry.gitlab.com/mosga/mosga: latest. Source code can be found at https://gitlab.com/mosga/mosga. Supplementary data are available at Bioinformatics online.

BnPIR: Brassica napus pan-genome information resource for 1689 accessions.

Brassica napus (B. napus) was originally formed ~7,500 years ago by interspecific hybridization between B. rape and B. oleracea (Chalhoub et al., 2014), which supplies approximately 13%-16% of the vegetable oil globally. B. napus serves as an excellent model for polyploid genomics and evolutionary research in plants. Brassica database (BRAD) has long been used for rapeseed genomic research, which provides genome browser and syntenic relationship for multiple Brassicaceae genomes (Wang et al., 2015).

DIPG-08. ELECTRONIC SEQUENCING PROVIDES OPTIMIZED QUANTIFICATION OF SERIAL, MULTI-GENE MOLECULAR RESPONSE IN THE CSF OF CHILDREN WITH HIGH-GRADE GLIOMA

BACKGROUNDFor pediatric high-grade glioma (pHGG), non-invasive methods for diagnosis and surveillance are needed. Tumors release DNA (tDNA) into cerebrospinal fluid (CSF), allowing for detection of tumor-associated mutations by CSF sampling. We hypothesized that direct, electronic analysis of tDNA with a novel, hand-held platform (Oxford Nanopore MinION) could quantify patient-specific CSF tDNA variant allele fraction (VAF) with improved speed and limit of detection compared to established methods.METHODSWe integrated required multi-timepoint (0, 2, and 6 months) correlate lumbar punctures (LP) in two ongoing pHGG clinical trials. Using Nanopore technology, we performed amplicon-based PCR on CSF tDNA for recurrent mutations from patient samples (n=19) and normal controls. VAF were determined via MinKNOW, Guppy, MiniMap2, and Integrated Genome Browser.RESULTSNanopore CSF tDNA demonstrated improved sensitivity (91%) when compare to NGS sequencing (50%). Nanopore analysis of serially diluted CSF sample demonstrated significantly lower limit of detection (attomolar) than typical NGS sample requirement (nanomolar). H3K27M mutation was reliably detected with 1,000x depth sequencing, which was achieved in less than 15 minutes of sequencing after amplification. Multiplexed Nanopore analysis of H3F3A and HIST1H3B was employed when H3 status was unknown. Serial CSF tDNA analysis confirmed multi-gene (H3F3A K27M, PIK3CA, and TP53) molecular remission in a 17-year-old with thalamic diffuse midline glioma that correlated with sustained clinical response to ONC201 (14 months and ongoing).CONCLUSIONSUse of a hand-held, electronic DNA analysis platform allows quantification of multi-gene molecular response with improved speed and limit of detection in the CSF of children with high-grade glioma.

GENCODE 2021.

The GENCODE project annotates human and mouse genes and transcripts supported by experimental data with high accuracy, providing a foundational resource that supports genome biology and clinical genomics. GENCODE annotation processes make use of primary data and bioinformatic tools and analysis generated both within the consortium and externally to support the creation of transcript structures and the determination of their function. Here, we present improvements to our annotation infrastructure, bioinformatics tools, and analysis, and the advances they support in the annotation of the human and mouse genomes including: the completion of first pass manual annotation for the mouse reference genome; targeted improvements to the annotation of genes associated with SARS-CoV-2 infection; collaborative projects to achieve convergence across reference annotation databases for the annotation of human and mouse protein-coding genes; and the first GENCODE manually supervised automated annotation of lncRNAs. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org.

Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer

We have observed overexpression of PACS-1, a cytosolic sorting protein in primary cervical tumors. Absence of exonic mutations and overexpression at the RNA level suggested a transcriptional and/or posttranscriptional regulation. University of California Santa Cruz genome browser analysis of PACS-1 micro RNAs (miR), revealed two 8-base target sequences at the 3' terminus for hsa-miR-34a and hsa-miR-449a. Quantitative RT-PCR and Northern blotting studies showed reduced or loss of expression of the two microRNAs in cervical cancer cell lines and primary tumors, indicating dysregulation of these two microRNAs in cervical cancer. Loss of PACS-1 with siRNA or exogenous expression of hsa-miR-34a or hsa-miR-449a in HeLa and SiHa cervical cancer cell lines resulted in DNA damage response, S-phase cell cycle arrest, and reduction in cell growth. Furthermore, the siRNA studies showed that loss of PACS-1 expression was accompanied by increased nuclear γH2AX expression, Lys382-p53 acetylation, and genomic instability. PACS-1 re-expression through LNA-hsa-anti-miR-34a or -449a or through PACS-1 cDNA transfection led to the reversal of DNA damage response and restoration of cell growth. Release of cells post 24-h serum starvation showed PACS-1 nuclear localization at G1-S phase of the cell cycle. Our results therefore indicate that the loss of hsa-miR-34a and hsa-miR-449a expression in cervical cancer leads to overexpression of PACS-1 and suppression of DNA damage response, resulting in the development of chemo-resistant tumors.

Whole exome sequencing analysis identifies genes and pathways in sporadic early‐onset Alzheimer’s disease

AbstractBackgroundSporadic early‐onset Alzheimer’s disease (EOAD) patients (onset age &lt; 65 years) do not harbor a known causative variant and have a heritability estimated to be 92‐100% (Barber et al. 2016). Here we performed whole exome sequencing (WES) to identify functional exonic variants in sporadic EOAD.MethodDNA was extracted and sequenced from blood samples of 109 Korean patients with EOAD or Mild Cognitive Impairment (MCI) younger than 65 years of age. Short‐read sequences from WES were mapped to the NCBI reference human genome (build 37) using BWA and GATK. All the variants were annotated with ANNOVAR. PolyPhen‐2 and SIFT were used to predict potential impact on protein structure or function of missense variants. After quality control procedures for samples and variants, we performed a case‐control association using PLINK on 109 Korean patients and 405 East Asia population from the 1000 Genomes Project.ResultThe genetic association analysis in a case‐control study design identified several sporadic EOAD susceptibility genes with missense variants with minor allele frequency (MAF) greater than 1%. A common exonic variant in LILRB2 had a significant p‐value of 1.036 × 10e ‐11 with MAF 0.11 compared with MAF = 0.395 in East Asian and MAF = 0.160 in cognitively normal Korean population (source: KRGDB genome browser). A common exonic variant in HLA‐DQB2 was also identified with a p‐value of 2.252 × 10e ‐08 with MAF 0.197 compared with MAF = 0.413 in East Asian and MAF = 0.34 in KRGDB. A common exonic variant in LIPC showed a marginal significance with a p‐value of 4.537 × 10e ‐05 with MAF = 0.0688 compared to MAF = 0.208 in East Asian and MAF = 0.12 in KRGDB. Other common exonic variants were found in TNR, ITGAX (p‐values &lt; 5.00xe ‐056. The protein‐protein interaction network analysis using STRING showed that LILRB2 has a direct interaction with ADAM10 and ITGAX, HLA‐DQB2 has a direct interaction with ITGAX that has a direct interaction with ADAM10, and LIPC has interactions with APP, SORL1 and CLU, which are known AD risk genes.ConclusionWhole‐exome sequencing analysis identified exonic variants associated with sporadic EOAD. Studying these genes and their pathways might lead us to a better understanding of the genetic architecture of sporadic EOAD.

FinaleDB: a browser and database of cell-free DNA fragmentation patterns.

SummaryCirculating cell-free DNA (cfDNA) is a promising biomarker for the diagnosis and prognosis of many diseases, including cancer. The genome-wide non-random fragmentation patterns of cfDNA are associated with the nucleosomal protection, epigenetic environment and gene expression in the cell types that contributed to cfDNA. However, current progress on the development of computational methods and understanding of molecular mechanisms behind cfDNA fragmentation patterns is significantly limited by the controlled-access of cfDNA whole-genome sequencing (WGS) dataset. Here, we present FinaleDB (FragmentatIoN AnaLysis of cEll-free DNA DataBase), a comprehensive database to host thousands of uniformly processed and curated de-identified cfDNA WGS datasets across different pathological conditions. Furthermore, FinaleDB comes with a fragmentation genome browser, from which users can seamlessly integrate thousands of other omics data in different cell types to experience a comprehensive view of both gene-regulatory landscape and cfDNA fragmentation patterns.Availability and implementationFinaleDB service: http://finaledb.research.cchmc.org/. FinaleDB source code: https://github.com/epifluidlab/finaledb_portal, https://github.com/epifluidlab/finaledb_workflow.Supplementary informationSupplementary data are available at Bioinformatics online.

Abstract PO-192: Exploring the contribution of introgressed ancient DNA to prostate cancer racial disparity

Abstract Introduction Prostate cancer is the most common cancer in men and there is racial disparity in prostate cancer incidence and mortality globally, with greater disease burden in men of African ancestry, followed by European ancestry and least in men of Asian ancestry. The etiology of prostate cancer is not fully understood but includes genetic and environmental factors. Present day non-Africans are reported to have introgressed DNA from Neanderthal and Denisovan ancestors. Over 170 prostate cancer associated single nucleotide polymorphisms (SNPs) have been identified from several genome-wide association studies (GWAS), with SNPS on chromosomes 2, 8 and 22 reported as showing variation between African and non-African men with prostate cancer. We performed analysis of prostate cancer associated SNPs on chromosomes 2, 8 and 22 to determine if DNA introgression could explain the racial variation. Methods We obtained data on prostate cancer associated SNPs from the GWAS catalog (https://www.ebi.ac.uk/gwas) and from reports that were not included in the catalog. Using an Ancient Genome Browser provided by the Max Plank Institute (https://www.eva.mpg.de/genetics/genome-projects/neandertal/index.html), we determined whether SNPs on chromosomes 2, 8 and 22 were present in African, Neanderthal or Denisovan genomes. Based on the results, we inferred that SNPs were introgressed if they were present in Neanderthal or Denisovan genomes but absent from African genomes. Results 49, 59 and 17 prostate cancer SNPs were reported in chromosomes 2, 8 and 22 respectively. 23/49 in ch2, 25/59 in c 8 and 9/17 in ch22 were present in in Neanderthal and or Denisovan genomes. SNPs in ch2 (rs13403657, rs12621278) and ch8 (rs7825414) were present in Neanderthal or Denisovan genomes but absent in African genomes. These SNPs lie in regions that have previously been reported to harbour introgressd DNA. Conclusion Our analyses identified prostate cancer associated SNPs that are likely to have been introgressed into present day non-Africans by extinct Neanderthal and Denisovan ancestors. Phenotypic changes caused by introgressed DNA could be contributing to racial disparities in prostate cancer in present day humans. Citation Format: Evi O. Useh, Suresh Venugopal, Chidi N. Molokwu. Exploring the contribution of introgressed ancient DNA to prostate cancer racial disparity [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-192.

14 Genome-wide association study of frozen sperm quality in cocks

Abstract Preservation of the genetic material of unique breeds of hens involves the use of semen cryobanks. The aim of the study was to search for genomic associations with rooster sperm quality after freezing. We took into account the decrease in sperm motility after thawing. Genotyping of 96 individuals (roosters) using the Affymetrix Axiom®600k Array chip was performed. Genomic data were obtained using the Plink 1.9 software. DNA samples were taken with genotyping quality at SNP loci more than 95%, SNP with MAF &amp;gt; 0.01. GWAS was performed using EMMAX. SNP information in the corresponding genes was determined using the genomic browsers NCBI and Ensembl. Assessment of rooster sperm quality showed high individual variability in total motility before freezing (20–95%), and after freezing (5–70%). Significant SNPs were detected on the chromosomes GGA1 (rs315598192, rs316943858), GGA2 (rs312981435), GGA3 (rs13694743), GGA11 (rs314024471), GGA19 (rs316346648), GGA22 (rs31797024248, rga31780824824, gga22 (rs3178082424). Candidate genes ZC3HC1, CACNA2D1, BCKDHB, AMFR, and GOSR1 were identified. The annotated genes were associated with cell cycle regulation, the formation of calcium cytoskeleton, and the formation of a multienzyme complex associated with the inner membrane of mitochondria, glycosylated transmembrane receptor. The experimental data and results can be used to study the localization of regions and genes associated with phenotypic traits of frozen sperm quality. Authors acknowledge financial support from Russian Science Foundation № 18-16-00071.

PSVII-26 Detection of selection signatures in Civil and Large White pig breeds

Abstract The detection of selection signatures can help to understand the mechanisms of artificial selection. The purpose of this work is to determine the selection signatures in Civil pig relatively Large White breed. The research was carried out on Large White of three breeding centers (LW_1_New=16, LW_2_New=12, LW_3_New=15) and Civilskay, bred in Russia on the basis of local pigs and Large White boars, (Civil=17). GeneSeek GGP Porcine HD BeadChip (San Diego, USA) was used. A heatmap plot of genomic relationship matrix (GRM) was used to evaluate genetic variability between populations. The signals of diversifying selection were detected using Fst and Smoothing Fst (R package Lokern). QTLs and genes were identified and annotated in the Ensembl genome browser (Sscrofa 11.1) (https://www.ensembl.org/index.html), Panther 15.0 (http://www.pantherdb.org/) and QTLdb (https://www.animalgenome.org/cgi-bin/QTLdb/index).Data visualization from heatmapplot (Fig.) showed that all individuals are grouped in relation to their groups. However, the groups LW_1_New, LW_3_New and CIVIL were separated from LW_2_New. We have selected LW_1_New, LW_3_New and CIVIL to identify the selection signatures. After smoothing of the data by moving average, top 0.1% of the observations were considered as pinpointing CIVIL-specific selection signals. As a result, genome regions with strong selection signals on SSC1:214634036-217738857, SSSC2:137533941-138048506, SSC4:24655041-30832595, SSC7:27386432-28655399 and SSC8:55806826-56299366 were found. In these areas, 535 QTLs have been identified, including 347 QTLs for Meat and Carcass Traits (the majority related to Backfat), 67 QTLs Production (Average daily gain or Body weight), 62 QTLs Health (Mean corpuscular volume, Actinobacillus pleuropneumoniae susceptibility et al.), 32 QTLs Reproduction (Teat number) and 27 QTLs Exterior (Leg conformation). In general, 32 genes are defined in these regions (SSC1-11; SSC2-5; SSC4-10; SSC7-3; SSC8-3) (Table). They are mainly involved in the following biological processes: metabolic (GO:0008152), cellular (GO:0009987) and biological regulation (GO:0065007). This research was supported by the Russian Scientific Foundation (RSF) within Project No. 19-16-00109.

Database construction for Vietnamese catfish genome

Molecular biological research plays an important role in aquaculture, contributes to the improvement ofbroodstocks efficiently. Recently, with the development of next-generation sequencing (NGS) technology,genomic studies have been rapidly increased, in which data organisation and management hold a crucialposition. After obtaining NGS sequencing data of Vietnamese catfish (Pangasianodon hypophthalmus), wehave analysed and annotated the catfish genome, from which we have constructed a database for efficientusage. The database is built upon open source software following a three-layer model (interface, Web serviceand database) with a convenient interface through Web browsers. Users can look up sequence and annotationdata as well as visualize sequences through the Jbrowse genome browser. This database is important resourcefor functional genome and genetic improvement of the catfish.

VarStack: a web tool for data retrieval to interpret somatic variants in cancer.

Advances in tumor genome sequencing created an urgent need for bioinformatics tools to support the interpretation of the clinical significance of the variants detected. VarStack is a web tool which is a base to retrieve somatic variant data relating to cancer from existing databases. VarStack incorporates data from several publicly available databases and presents them with an easy-to-navigate user interface. It currently supports data from the Catalogue of Somatic Mutations in Cancer, gnomAD, cBioPortal, ClinVar, OncoKB, CiViC and UCSC Genome Browser. It retrieves the data from these databases and returns them back to the user in a fraction of the time it would take to manually navigate each site independently. Users submit a variant with a gene symbol, peptide change and coding sequence change. They may select a variety of tumor-specific studies in cBioPortal to search through in addition to their original query. The results from the databases are presented in tabs. Users can export the results as an Excel file. VarStack also has the batch search feature in which the user can submit a list of variants and download an Excel file with the data from the databases. With the batch search and data download options, users can easily incorporate VarStack into their workflow or tools. VarStack saves time by providing somatic variant information to the user from multiple databases in an easy-to-export and interpretable format. VarStack is freely available under https://varstack.brown.edu.

The NanDeSyn database for Nannochloropsis systems and synthetic biology.

Nannochloropsis species, unicellular industrial oleaginous microalgae, are model organisms for microalgal systems and synthetic biology. To facilitate community-based annotation and mining of the rapidly accumulating functional genomics resources, we have initiated an international consortium and present a comprehensive multi-omics resource database named Nannochloropsis Design and Synthesis (NanDeSyn; http://nandesyn.single-cell.cn). Via the Tripal toolkit, it features user-friendly interfaces hosting genomic resources with gene annotations and transcriptomic and proteomic data for six Nannochloropsis species, including two updated genomes of Nannochloropsis oceanica IMET1 and Nannochloropsis salina CCMP1776. Toolboxes for search, Blast, synteny view, enrichment analysis, metabolic pathway analysis, a genome browser, etc. are also included. In addition, functional validation of genes is indicated based on phenotypes of mutants and relevant bibliography. Furthermore, epigenomic resources are also incorporated, especially for sequencing of small RNAs including microRNAs and circular RNAs. Such comprehensive and integrated landscapes of Nannochloropsis genomics and epigenomics will promote and accelerate community efforts in systems and synthetic biology of these industrially important microalgae.

Accessing NCBI data using the NCBI Sequence Viewer and Genome Data Viewer (GDV).

The National Center for Biotechnology Information (NCBI) is an archive providing free access to a wide range and large volume of biological sequence data and literature. Staff scientists at NCBI analyze user-submitted data in the archive, producing gene and SNP annotation and generating sequence alignment tools. NCBI's flagship genome browser, Genome Data Viewer (GDV), displays our in-house RefSeq annotation; is integrated with other NCBI resources such as Gene, dbGaP, and BLAST; and provides a platform for customized analysis and visualization. Here, we describe how members of the biomedical research community can use GDV and the related NCBI Sequence Viewer (SV) to access, analyze, and disseminate NCBI and custom biomedical sequence data. In addition, we report how users can add SV to their own web pages to create a custom graphical sequence display without the need for infrastructure investments or back-end deployments.