GDS: A Genomic Database for Strawberries (Fragaria spp.)

Strawberry species (Fragaria spp.) are known as the “queen of fruits” and are cultivated around the world. Over the past few years, eight strawberry genome sequences have been released. The reuse of these large amount of genomic data, and the more large-scale comparative analyses are very challenging to both plant biologists and strawberry breeders. To promote the reuse and exploration of strawberry genomic data and enable extensive analyses using various bioinformatics tools, we have developed the Genome Database for Strawberry (GDS). This platform integrates the genome collection, storage, integration, analysis, and dissemination of large amounts of data for researchers engaged in the study of strawberry. We collected and formatted the eight published strawberry genomes. We constructed the GDS based on Linux, Apache, PHP and MySQL. Different bioinformatic software were integrated. The GDS contains data from eight strawberry species, as well as multiple tools such as BLAST, JBrowse, synteny analysis, and gene search. It has a designed interface and user-friendly tools that perform a variety of query tasks with a few simple operations. In the future, we hope that the GDS will serve as a community resource for the study of strawberries.

ReGSP: a visualized application for homology-based gene searching and plotting using multiple reference sequences

The massively parallel nature of next-generation sequencing technologies has contributed to the generation of massive sequence data in the last two decades. Deciphering the meaning of each generated sequence requires multiple analysis tools, at all stages of analysis, from the reads stage all the way up to the whole-genome level. Homology-based approaches based on related reference sequences are usually the preferred option for gene and transcript prediction in newly sequenced genomes, resulting in the popularity of a variety of BLAST and BLAST-based tools. For organelle genomes, a single-reference–based gene finding tool that uses grouping parameters for BLAST results has been implemented in the Genome Search Plotter (GSP). However, this tool does not accept multiple and user-customized reference sequences required for a broad homology search. Here, we present multiple Reference–based Gene Search and Plot (ReGSP), a simple and convenient web tool that accepts multiple reference sequences for homology-based gene search. The tool incorporates cPlot, a novel dot plot tool, for illustrating nucleotide sequence similarity between the query and the reference sequences. ReGSP has an easy-to-use web interface and is freely accessible at https://ds.mju.ac.kr/regsp.

Taxonomic Analysis of Oral Microbiome during Orthodontic Treatment

Background. Orthodontic appliances induce significant changes in the oral microbiome, but this shift in microbial composition has not been well established by the available evidence yet. Objectives. To perform a systematic review of existing literature in order to assess the taxonomic microbial changes in orthodontic patients during Fixed Appliance Treatment (FAT) and Clear Aligner Treatment (CAT), using next-generation sequencing (NGS) technique of the bacterial 16S rRNA gene. Search Methods and Selection Criteria. The search for articles was carried out in PubMed, including articles published in English until May 2021. They included every human study report potentially relevant to the review. Data Collection and Analysis. After duplicate study selection and data extraction procedures according to the PICOS scheme, the methodological quality of the included papers was assessed by the Swedish Council on Technology Assessment in Health Care Criteria for Grading Assessed Studies (SBU) method. Results. The initial search identified 393 articles, 74 of which were selected by title and abstract. After full-text reading, six articles were selected according to inclusion criteria. The evidence quality for all the studies was moderate. Conclusions. Orthodontic treatment seems to transiently affect the composition of subgingival microbiome, although not salivary, maintaining a stable microbial diversity. Different results were found in the shift of microbiome between plaque and saliva, depending on the type of orthodontic treatment. This review should be interpreted with some caution because of the number, quality, and heterogeneity of the included studies.

SHOOT: phylogenetic gene search and ortholog inference

Determining the evolutionary relationships between gene sequences is fundamental to comparative biological research. However, conducting such analyses requires a high degree of technical proficiency in several computational tools including gene family construction, multiple sequence alignment, and phylogenetic inference. Here we present SHOOT, an easy to use phylogenetic search engine for fast and accurate phylogenetic analysis of biological sequences. SHOOT searches a user-provided query sequence against a database of phylogenetic trees of gene sequences (gene trees) and returns a gene tree with the given query sequence correctly grafted within it. We show that SHOOT can perform this search and placement with comparable speed to a conventional BLAST search. We demonstrate that SHOOT phylogenetic placements are as accurate as conventional multiple sequence alignment and maximum likelihood tree inference approaches. We further show that SHOOT can be used to identify orthologs with equivalent accuracy to conventional orthology inference methods. In summary, SHOOT is an accurate and fast tool for complete phylogenetic analysis of novel query sequences. An easy to use webserver is available online at www.shoot.bio.

PCRMS: a database of predicted cis-regulatory modules and constituent transcription factor binding sites in genomes

More accurate and more complete predictions of cis-regulatory modules (CRMs) and constituent transcriptional factor (TF) binding sites (TFBSs) in genomes can facilitate characterizing functions of regulatory sequences. Here, we developed a database PCRMS (https://cci-bioinfo.uncc.edu) that stores highly accurate and unprecedentedly complete maps of predicted CRMs and TFBSs in the human and mouse genomes. The web interface allows the user to browse CRMs and TFBSs in an organism, find the closest CRMs to a gene, search CRMs around a gene, and find all TFBSs of a TF. PCRMS can be a useful resource for the research community to characterize regulatory genomes.

Next-Generation Sequencing for Non-Ampullary Duodenal Carcinoma Suggesting the Existence of an Adenoma-Carcinoma Sequence

Duodenal tumors with a sporadic adenoma-carcinoma sequence are extremely rare. For such clinically suspected cases without a specific family history, performing a comprehensive gene search is important to understand the germline mutation background. We present a 68-year-old woman without a genetic or familial history of familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, or Lynch syndrome who presented to Kosei Hospital, Japan, with exertional dyspnea induced by abdominal pain lasting 3 weeks. A duodenal tumor was suspected by contrast-enhanced computed tomography. Esophagogastroduodenoscopy showed a lesion accompanied by a white microprotuberance on the descending part of the duodenum opposite the papilla, with a giant ulcerative lesion at the center of the white lesion. Biopsy revealed a low-grade adenoma, high-grade adenoma, and adenocarcinoma. Immunohistochemical analysis of the adenoma and adenocarcinoma showed Ki-67, p53, cytokeratin 20, caudal-type homeobox 2, and carcinoembryonic antigen positivity and cytokeratin 7 negativity. The findings suggested the presence of an adenoma-adenocarcinoma sequence in duodenal carcinoma. However, in the mutational analysis using next-generation sequencing, c.4348C>T (p.Arg1450Ter) mutation in APC was detected in all normal mucosal, adenoma, and carcinoma tissues. This mutation is common in FAP patients. Even if the presence of an adenoma-adenocarcinoma sequence in duodenal carcinoma is suggested in cases without a familial FAP history, as in this case, genetic analysis may reveal FAP. Thus, performing a comprehensive genetic analysis of duodenal carcinoma patients with a possible adenoma-carcinoma sequence is necessary to explore their genetic background.

Candidate Gene Discovery in Hereditary Colorectal Cancer and Polyposis Syndromes–Considerations for Future Studies

To discover novel high-penetrant risk loci for hereditary colorectal cancer (hCRC) and polyposis syndromes many whole-exome and whole-genome sequencing (WES/WGS) studies have been performed. Remarkably, these studies resulted in only a few novel high-penetrant risk genes. Given this observation, the possibility and strategy to identify high-penetrant risk genes for hCRC and polyposis needs reconsideration. Therefore, we reviewed the study design of WES/WGS-based hCRC and polyposis gene discovery studies (n = 37) and provide recommendations to optimize discovery and validation strategies. The group of genetically unresolved patients is phenotypically heterogeneous, and likely composed of distinct molecular subtypes. This knowledge advocates for the screening of a homogeneous, stringently preselected discovery cohort and obtaining multi-level evidence for variant pathogenicity. This evidence can be collected by characterizing the molecular landscape of tumors from individuals with the same affected gene or by functional validation in cell-based models. Together, the combined approach of a phenotype-driven, tumor-based candidate gene search might elucidate the potential contribution of novel genetic predispositions in genetically unresolved hCRC and polyposis.

Panton-Valentine Leukocidin-Producing Staphylococcus aureus Infection: A Case Series

Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) is associated with relapsing multifocal skin and soft tissue infections (SSTI), necrotizing pneumonia (NP) and severe musculoskeletal infections. Epidemiology is underknown and underdiagnosis is likely. Recent travel abroad, case clustering and relapsing disease are often reported. We reviewed all cases of PVL-SA infection diagnosed at our center, and found 21 cases over a 43-month period. Most patients were adult males, had relevant travel history, reported recurrent disease and presented with SSTI. Etiologic diagnosis took up to five years; meanwhile, 42% of patients had antibiotic treatments. Draining procedures were required in 43% of patients and intensive care support in 19%. All patients recovered. Methicillin-resistance prevalence was 24%. Only 2/13 decolonized patients had posterior relapsing SSTI, both with likely infected contacts. PVL-SA infection’s severity and impact are clear, even in small case series as ours. Physician awareness and active PVL-gene search are crucial for an adequate management.

Autoimmune Mechanisms of Interferon Hypersensitivity and Neurodegenerative Diseases: Down Syndrome

Down syndrome (DS), also known as trisomy 21 (T21), is associated with interferon (IFN) hypersensitivity, as well as predilections for Alzheimer’s dementia (AD) and various autoimmune diseases. IFN-α and IFN-γ receptors are encoded on chromosome 21 (Ch21). It remains unclear how other Ch21 genes contribute to the neuropathological features of DS/T21. This study tests the hypothesis that identifying IFN-stimulated response element (ISRE) control sites on Ch21 will mark novel candidate genes for DS/T21-related IFN hypersensitivity and neuropathology not previously reported to be associated with IFN functions. We performed whole chromosome searches of online databases. The general ISRE consensus and gamma interferon activation consensus sequences (GAS) were used for identifying IFN-stimulated response elements. Candidate genes were defined as those possessing two or more ISRE and/or GAS control sites within and/or upstream of the transcription start site. A literature search of gene functions was used to select the candidate genes most likely to explain neuropathology associated with IFN hypersensitivity. DOPEY2, TMEM50B, PCBP3, RCAN1, and SIM2 were found to meet the aforementioned gene search and functional criteria. These findings suggest that DOPEY2, TMEM50B, PCBP3, RCAN1, and SIM2 are genes which may be dysregulated in DS/T21 and may therefore serve as novel targets for treatments aimed at ameliorating the neuropathological features of DS/T21. Future studies should determine whether these genes are dysregulated in patients with DS, DS-related AD, and autoimmune diseases.

Multiple QTL Mapping in Autopolyploids: A Random-Effect Model Approach with Application in a Hexaploid Sweetpotato Full-Sib Population

In developing countries, the sweetpotato, Ipomoea batatas (L.) Lam. (2n=6x=90), is an important autopolyploid species, both socially and economically. However, quantitative trait loci (QTL) mapping has remained limited due to its genetic complexity. Current fixed-effect models can fit only a single QTL and are generally hard to interpret. Here, we report the use of a random-effect model approach to map multiple QTL based on score statistics in a sweetpotato biparental population (‘Beauregard’ × ‘Tanzania’) with 315 full-sibs. Phenotypic data were collected for eight yield component traits in six environments in Peru, and jointly adjusted means were obtained using mixed-effect models. An integrated linkage map consisting of 30,684 markers distributed along 15 linkage groups (LGs) was used to obtain the genotype conditional probabilities of putative QTL at every centiMorgan position. Multiple interval mapping was performed using our R package QTLpoly and detected a total of 13 QTL, ranging from none to four QTL per trait, which explained up to 55% of the total variance. Some regions, such as those on LGs 3 and 15, were consistently detected among root number and yield traits, and provided a basis for candidate gene search. In addition, some QTL were found to affect commercial and noncommercial root traits distinctly. Further best linear unbiased predictions were decomposed into additive allele effects and were used to compute multiple QTL-based breeding values for selection. Together with quantitative genotyping and its appropriate usage in linkage analyses, this QTL mapping methodology will facilitate the use of genomic tools in sweetpotato breeding as well as in other autopolyploids.