Genomic Repositories Research Articles

Investigation of the clinical significance and molecular mechanism of miR‑21‑5p in hepatocellular carcinoma: A systematic review based on 24 studies and bioinformatics investigation

To investigate the prospective roles and the clinicopathological application of microRNA-21-5p (miR-21-5p) in hepatocellular carcinoma (HCC), the present review is based on 24 studies and bioinformatics investigation. Firstly, HCC-associated miR-21-5p data were aggregated from literature databases and two public genomic data repositories, including the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Potential target genes of miR-21-5p in HCC were identified using TCGA and GEO, Natural Language Processing and 14 online software packages. The oncogenic roles of these target genes was probed for understanding using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. Hub genes were further investigated by protein-protein interaction network (PPI) analysis. Comprehensive meta-analysis, including 10 microarrays from GEO datasets, 13 literature studies and TCGA-based RNA sequencing data, indicated a reliable diagnostic capacity of miR-21-5p [area under the curve (AUC), 0.887; sensitivity, 0.78% and specificity, 0.79%]. The healthy control group (AUC, 0.926; sensitivity, 0.87% and specificity, 0.82%) demonstrated high diagnostic capacity of miR-21-5p compared with the chronic hepatitis B infection group (AUC, 0.904; sensitivity, 0.75% and specificity, 0.84%). A total of 10 significant enrichment pathways were indicated by KEGG analysis, with cytokine-cytokine receptor interaction exhibiting the highest score. A total of 5 genes, hepatocyte growth factor, forkhead box O1 (FOXO1), thrombospondin 1, estrogen receptor 1 (ESR1) and C-X-C motif chemokine ligand 12 were selected from 39 overlapping genes, according to the PPI network. Target genes were assembled in GO terms associated with ‘response to chemical stimulus’, ‘cell surface’ and ‘growth factor binding’. In particular, low expression of FOXO1 and ESR1 was associated with miR-21-5p expression. In conclusion, upregulated expression of miR-21-5p may be a functional regulator of the metabolism or apoptosis in HCC and a novel tumor marker for the early diagnosis of HCC.

The insulin-like growth factor 2 gene and locus in nonmammalian vertebrates: Organizational simplicity with duplication but limited divergence in fish

The small, secreted peptide, insulin-like growth factor 2 (IGF2), is essential for fetal and prenatal growth in humans and other mammals. Human IGF2 and mouse Igf2 genes are located within a conserved linkage group and are regulated by parental imprinting, with IGF2/Igf2 being expressed from the paternally derived chromosome, and H19 from the maternal chromosome. Here, data retrieved from genomic and gene expression repositories were used to examine the Igf2 gene and locus in 8 terrestrial vertebrates, 11 ray-finned fish, and 1 lobe-finned fish representing >500 million years of evolutionary diversification. The analysis revealed that vertebrate Igf2 genes are simpler than their mammalian counterparts, having fewer exons and lacking multiple gene promoters. Igf2 genes are conserved among these species, especially in protein-coding regions, and IGF2 proteins also are conserved, although less so in fish than in terrestrial vertebrates. The Igf2 locus in terrestrial vertebrates shares additional genes with its mammalian counterparts, including tyrosine hydroxylase (Th), insulin (Ins), mitochondrial ribosomal protein L23 (Mrpl23), and troponin T3, fast skeletal type (Tnnt3), and both Th and Mrpl23 are present in the Igf2 locus in fish. Taken together, these observations support the idea that a recognizable Igf2 was present in the earliest vertebrate ancestors, but that other features developed and diversified in the gene and locus with speciation, especially in mammals. This study also highlights the need for correcting inaccuracies in genome databases to maximize our ability to accurately assess contributions of individual genes and multigene families toward evolution, physiology, and disease.

Erratum for Sanders et al., "FusoPortal: an Interactive Repository of Hybrid MinION-Sequenced Fusobacterium Genomes Improves Gene Identification and Characterization".

Volume 3, no. 4, e00228-18, 2018, [https://doi.org/10.1128/mSphere.00228-18][1]. Page 5 of the PDF, Table 1, last row, last column: “21,215” should be “2,125.” [1]: /lookup/doi/10.1128/mSphere.00228-18

FusoPortal: an Interactive Repository of Hybrid MinION-Sequenced Fusobacterium Genomes Improves Gene Identification and Characterization.

Here we present FusoPortal, an interactive repository of Fusobacterium genomes that were sequenced using a hybrid MinION long-read sequencing pipeline, followed by assembly and annotation using a diverse portfolio of predominantly open-source software. Significant efforts were made to provide genomic and bioinformatic data as downloadable files, including raw sequencing reads, genome maps, gene annotations, protein functional analysis and classifications, and a custom BLAST server for FusoPortal genomes. FusoPortal has been initiated with eight complete genomes, of which seven were previously only drafts that ranged from 24 to 67 contigs. We have showcased that the genomes in FusoPortal provide accurate open reading frame annotations and have corrected a number of large (>3-kb) genes that were previously misannotated due to contig boundaries. In summary, FusoPortal (http://fusoportal.org) is the first database of MinION-sequenced and completely assembled Fusobacterium genomes, and this central Fusobacterium genomic and bioinformatic resource will aid the scientific community in developing a deeper understanding of how this human pathogen contributes to an array of diseases, including periodontitis and colorectal cancer.IMPORTANCE In this report, we describe a hybrid MinION whole-genome sequencing pipeline and the genomic characteristics of the first eight Fusobacterium strains deposited in the FusoPortal database. This collection of highly accurate and complete genomes drastically improves upon previous multicontig assemblies by correcting and newly identifying a significant number of open reading frames. We believe that the availability of this resource will result in the discovery of proteins and molecular mechanisms used by an oral pathogen, with the potential to further our understanding of how Fusobacterium nucleatum contributes to a repertoire of diseases, including periodontitis, preterm birth, and colorectal cancer.

SAFETY: Secure gwAs in Federated Environment through a hYbrid Solution.

Recent studies demonstrate that effective healthcare can benefit from using the human genomic information. Consequently, many institutions are using statistical analysis of genomic data, which are mostly based on genome-wide association studies (GWAS). GWAS analyze genome sequence variations in order to identify genetic risk factors for diseases. These studies often require pooling data from different sources together in order to unravel statistical patterns, and relationships between genetic variants and diseases. Here, the primary challenge is to fulfill one major objective: accessing multiple genomic data repositories for collaborative research in a privacy-preserving manner. Due to the privacy concerns regarding the genomic data, multi-jurisdictional laws and policies of cross-border genomic data sharing are enforced among different countries. In this article, we present SAFETY, a hybrid framework, which can securely perform GWAS on federated genomic datasets using homomorphic encryption and recently introduced secure hardware component of Intel Software Guard Extensions to ensure high efficiency and privacy at the same time. Different experimental settings show the efficacy and applicability of such hybrid framework in secure conduction of GWAS. To the best of our knowledge, this hybrid use of homomorphic encryption along with Intel SGX is not proposed to this date. SAFETY is up to 4.82 times faster than the best existing secure computation technique.

Genome Annotation Generator: a simple tool for generating and correcting WGS annotation tables for NCBI submission.

BackgroundOne of the most overlooked, yet critical, components of a whole genome sequencing (WGS) project is the submission and curation of the data to a genomic repository, most commonly the National Center for Biotechnology Information (NCBI). While large genome centers or genome groups have developed software tools for post-annotation assembly filtering, annotation, and conversion into the NCBI’s annotation table format, these tools typically require back-end setup and connection to an Structured Query Language (SQL) database and/or some knowledge of programming (Perl, Python) to implement. With WGS becoming commonplace, genome sequencing projects are moving away from the genome centers and into the ecology or biology lab, where fewer resources are present to support the process of genome assembly curation. To fill this gap, we developed software to assess, filter, and transfer annotation and convert a draft genome assembly and annotation set into the NCBI annotation table (.tbl) format, facilitating submission to the NCBI Genome Assembly database. This software has no dependencies, is compatible across platforms, and utilizes a simple command to perform a variety of simple and complex post-analysis, pre-NCBI submission WGS project tasks.FindingsThe Genome Annotation Generator is a consistent and user-friendly bioinformatics tool that can be used to generate a .tbl file that is consistent with the NCBI submission pipelineConclusionsThe Genome Annotation Generator achieves the goal of providing a publicly available tool that will facilitate the submission of annotated genome assemblies to the NCBI. It is useful for any individual researcher or research group that wishes to submit a genome assembly of their study system to the NCBI.

DBBQs: dataBase of Bacterial Quality scores

BackgroundIt is well-known that genome sequencing technologies are becoming significantly cheaper and faster. As a result of this, the exponential growth in sequencing data in public databases allows us to explore ever growing large collections of genome sequences. However, it is less known that the majority of available sequenced genome sequences in public databases are not complete, drafts of varying qualities. We have calculated quality scores for around 100,000 bacterial genomes from all major genome repositories and put them in a fast and easy-to-use database.ResultsProkaryotic genomic data from all sources were collected and combined to make a non-redundant set of bacterial genomes. The genome quality score for each was calculated by four different measurements: assembly quality, number of rRNA and tRNA genes, and the occurrence of conserved functional domains. The dataBase of Bacterial Quality scores (dBBQs) was designed to store and retrieve quality scores. It offers fast searching and download features which the result can be used for further analysis. In addition, the search results are shown in interactive JavaScript chart framework using DC.js. The analysis of quality scores across major public genome databases find that around 68% of the genomes are of acceptable quality for many uses.ConclusionsdBBQs (available at http://arc-gem.uams.edu/dbbqs) provides genome quality scores for all available prokaryotic genome sequences with a user-friendly Web-interface. These scores can be used as cut-offs to get a high-quality set of genomes for testing bioinformatics tools or improving the analysis. Moreover, all data of the four measurements that were combined to make the quality score for each genome, which can potentially be used for further analysis. dBBQs will be updated regularly and is freely use for non-commercial purpose.

Core Clinical Data Elements for Cancer Genomic Repositories: A Multi-stakeholder Consensus

The Center for Medical Technology Policy and the Molecular Evidence Development Consortium gathered a diverse group of more than 50 stakeholders to develop consensus on a core set of data elements and values essential to understanding the clinical utility of molecularly targeted therapies in oncology.

Gb4gv: a genome browser for geminivirus.

BackgroundGeminiviruses (family Geminiviridae) are prevalent plant viruses that imperil agriculture globally, causing serious damage to the livelihood of farmers, particularly in developing countries. The virus evolves rapidly, attributing to its single-stranded genome propensity, resulting in worldwide circulation of diverse and viable genomes. Genomics is a prominent approach taken by researchers in elucidating the infectious mechanism of the virus. Currently, the NCBI Viral Genome website is a popular repository of viral genomes that conveniently provides researchers a centralized data source of genomic information. However, unlike the genome of living organisms, viral genomes most often maintain peculiar characteristics that fit into no single genome architecture. By imposing a unified annotation scheme on the myriad of viral genomes may downplay their hallmark features. For example, the viron of begomoviruses prevailing in America encapsulates two similar-sized circular DNA components and both are required for systemic infection of plants. However, the bipartite components are kept separately in NCBI as individual genomes with no explicit association in linking them. Thus, our goal is to build a comprehensive Geminivirus genomics database, namely gb4gv, that not only preserves genomic characteristics of the virus, but also supplements biologically relevant annotations that help to interrogate this virus, for example, the targeted host, putative iterons, siRNA targets, etc.MethodsWe have employed manual and automatic methods to curate 508 genomes from four major genera of Geminiviridae, and 161 associated satellites obtained from NCBI RefSeq and PubMed databases.ResultsThese data are available for free access without registration from our website. Besides genomic content, our website provides visualization capability inherited from UCSC Genome Browser.DiscussionWith the genomic information readily accessible, we hope that our database will inspire researchers in gaining a better understanding of the incredible degree of diversity of these viruses, and of the complex relationships within and between the different genera in the Geminiviridae.Availability and ImplementationThe database can be found at: http://gb4gv.lafayette.edu.

Block Graphs in Practice

Motivated by the rapidly increasing size of genomic databases, code repositories and versioned texts, several compression schemes have been proposed that work well on highly-repetitive strings and also support fast random access: e.g., LZ-End, RLZ, GDC, augmented SLPs, and block graphs. Block graphs have good worst-case bounds but it has been an open question whether they are practical. We describe an implementation of block graphs that, for several standard datasets, provides better compression and faster random access than competing schemes.

The international diffuse intrinsic pontine glioma registry: an infrastructure to accelerate collaborative research for an orphan disease.

Diffuse intrinsic pontine glioma (DIPG), a rare, often fatal childhood brain tumor, remains a major therapeutic challenge. In 2012, investigators, funded by the DIPG Collaborative (a philanthropic partnership among 29 private foundations), launched the International DIPG Registry (IDIPGR) to advance understanding of DIPG. Comprised of comprehensive deidentified but linked clinical, imaging, histopathological, and genomic repositories, the IDIPGR uses standardized case report forms for uniform data collection; serial imaging and histopathology are centrally reviewed by IDIPGR neuro-radiologists and neuro-pathologists, respectively. Tissue and genomic data, and cell cultures derived from autopsies coordinated by the IDIPGR are available to investigators for studies approved by the Scientific Advisory Committee. From April 2012 to December 2016, 670 patients diagnosed with DIPG have been enrolled from 55 participating institutions in the US, Canada, Australia and New Zealand. The radiology repository contains 3558 studies from 448 patients. The pathology repository contains tissue on 81 patients with another 98 samples available for submission. Fresh DIPG tissue from seven autopsies has been sent to investigators to develop primary cell cultures. The bioinformatics repository contains next-generation sequencing data on 66 tumors. Nine projects using data/tissue from the IDIPGR by 13 principle investigators from around the world are now underway. The IDIPGR, a successful alliance among philanthropic agencies and investigators, has developed and maintained a highly collaborative, hypothesis-driven research infrastructure for interdisciplinary and translational projects in DIPG to improve diagnosis, response assessment, treatment and outcome for patients.

Colonic Spirochetes: What Has Genomics Taught Us?

The 'colonic' spirochetes assigned to the genus Brachyspira are slow-growing anaerobic bacteria. The genus includes both pathogenic and non-pathogenic species, and these variously colonise the large intestines of different species of birds and animals, including humans. Scientific understanding of the physiology and molecular biology of Brachyspira spp. remains very limited compared with that of other pathogenic spirochetes, and there are few descriptions of successful genetic manipulations undertaken to investigate gene function. An important boost to knowledge occurred in 2009 when, for the first time, the whole genome sequence of a Brachyspira strain (Brachyspira hyodysenteriae strain WA1) was obtained. The genomics analysis provided a significant increase in knowledge: for example, a previously unknown ~36Kb plasmid was discovered and metabolic pathways were constructed. The study also revealed likely acquisition of genes involved in transport and central metabolic functions from other enteric bacterial species. Four subsequent publications have provided a similarly detailed analysis of other Brachyspira genomes, but of these only two included more than one strain of a species (20 strains of B. hyodysenteriae in one and three strains of B. pilosicoli in the other). Since then, more Brachyspira genomes have been made publicly available, with the sequences of at least one representative of each of the nine officially recognised species deposited at public genome repositories. All species have a single circular chromosome varying in size from ~2.5 to 3.3Mb, with a C+G content of around 27%. In this chapter, we summarise the current knowledge and present a preliminary comparative genomic analysis conducted on 56 strains covering the official Brachyspira species. Besides providing detailed genetic maps of the bacteria, this analysis has revealed gene island rearrangements, putative phenotypes (including antimicrobial drug resistance) and genetic mutation mechanisms that enable brachyspires to evolve and respond to stress. The application of Next-Generation Sequencing (NGS) to generate genomic data from many more Brachyspira species and strains increasing will improve our understanding of these enigmatic spirochetes.

A Dexamethasone-regulated Gene Signature Is Prognostic for Poor Survival in Glioblastoma Patients.

Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. We utilized 3 independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in The Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data databases. In silico Connectivity Map analysis identified camptothecin as antagonist to dexamethasone-induced negative effects. Pathway analyses predicted an activation of dexamethasone network (z-score: 2.908). Top activated canonical pathways included "role of breast cancer 1 in DNA damage response" (P=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when coincubated with dexamethasone. Altered cellular functions included cell movement, cell survival, and apoptosis with z-scores of 2.815, 5.137, and -3.122, respectively. CCAAT/enhancer binding protein beta (CEBPB) was activated in a dose dependent manner specifically in slow-dividing "stem-like" cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk scores had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone-induced oncogenic effects. Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value in patients. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects.

TP53 Variations in Human Cancers: New Lessons from the IARC TP53 Database and Genomics Data.

TP53 gene mutations are one of the most frequent somatic events in cancer. The IARC TP53 Database (http://p53.iarc.fr) is a popular resource that compiles occurrence and phenotype data on TP53 germline and somatic variations linked to human cancer. The deluge of data coming from cancer genomic studies generates new data on TP53 variations and attracts a growing number of database users for the interpretation of TP53 variants. Here, we present the current contents and functionalities of the IARC TP53 Database and perform a systematic analysis of TP53 somatic mutation data extracted from this database and from genomic data repositories. This analysis showed that IARC has more TP53 somatic mutation data than genomic repositories (29,000 vs. 4,000). However, the more complete screening achieved by genomic studies highlighted some overlooked facts about TP53 mutations, such as the presence of a significant number of mutations occurring outside the DNA-binding domain in specific cancer types. We also provide an update on TP53 inherited variants including the ones that should be considered as neutral frequent variations. We thus provide an update of current knowledge on TP53 variations in human cancer as well as inform users on the efficient use of the IARC TP53 Database.

GEE: An Informatics Tool for Gene Expression Data Explore.

ObjectivesMajor public high-throughput functional genomic data repositories, including the Gene Expression Omnibus (GEO) and ArrayExpress have rapidly expanded. As a result, a large number of diverse high-throughput functional genomic data retrieval systems have been developed. However, high-throughput functional genomic data retrieval remains challenging.MethodsWe developed Gene Expression data Explore (GEE), the first powerful, flexible web and mobile search application for searching whole-genome epigenetic data and microarray data in public databases, such as GEO and ArrayExpress.ResultsGEE provides an elaborate, convenient interface of query generation competences not available via various high-throughput functional genomic data retrieval systems, including GEO, ArrayExpress, and Atlas. In particular, GEE provides a suitable query generator using eVOC, the Experimental Factor Ontology (EFO), which is well represented with a variety of high-throughput functional genomic data experimental conditions. In addition, GEE provides an experimental design query constructor (EDQC), which provides elaborate retrieval filter conditions when the user designs real experiments.ConclusionsThe web version of GEE is available at http://www.snubi.org/software/gee, and its app version is available from the Apple App Store.

DFAST and DAGA: web-based integrated genome annotation tools and resources.

Quality assurance and correct taxonomic affiliation of data submitted to public sequence databases have been an everlasting problem. The DDBJ Fast Annotation and Submission Tool (DFAST) is a newly developed genome annotation pipeline with quality and taxonomy assessment tools. To enable annotation of ready-to-submit quality, we also constructed curated reference protein databases tailored for lactic acid bacteria. DFAST was developed so that all the procedures required for DDBJ submission could be done seamlessly online. The online workspace would be especially useful for users not familiar with bioinformatics skills. In addition, we have developed a genome repository, DFAST Archive of Genome Annotation (DAGA), which currently includes 1,421 genomes covering 179 species and 18 subspecies of two genera, Lactobacillus and Pediococcus, obtained from both DDBJ/ENA/GenBank and Sequence Read Archive (SRA). All the genomes deposited in DAGA were annotated consistently and assessed using DFAST. To assess the taxonomic position based on genomic sequence information, we used the average nucleotide identity (ANI), which showed high discriminative power to determine whether two given genomes belong to the same species. We corrected mislabeled or misidentified genomes in the public database and deposited the curated information in DAGA. The repository will improve the accessibility and reusability of genome resources for lactic acid bacteria. By exploiting the data deposited in DAGA, we found intraspecific subgroups in Lactobacillus gasseri and Lactobacillus jensenii, whose variation between subgroups is larger than the well-accepted ANI threshold of 95% to differentiate species. DFAST and DAGA are freely accessible at https://dfast.nig.ac.jp.

A human 3'UTR clone collection to study post-transcriptional gene regulation.

Background3′untranslated regions (3′UTRs) are poorly understood portions of eukaryotic mRNAs essential for post-transcriptional gene regulation. Sequence elements in 3′UTRs can be target sites for regulatory molecules such as RNA binding proteins and microRNAs (miRNAs), and these interactions can exert significant control on gene networks. However, many such interactions remain uncharacterized due to a lack of high-throughput (HT) tools to study 3′UTR biology. HT cloning efforts such as the human ORFeome exemplify the potential benefits of genomic repositories for studying human disease, especially in relation to the discovery of biomarkers and targets for therapeutic agents. Currently there are no publicly available human 3′UTR libraries. To address this we have prepared the first version of the human 3′UTRome (h3′UTRome v1) library. The h3′UTRome is produced to a single high quality standard using the same recombinational cloning technology used for the human ORFeome, enabling universal operating methods and high throughput experimentation. The library is thoroughly sequenced and annotated with simple online access to information, and made publically available through gene repositories at low cost to all scientists with minimal restriction.ResultsThe first release of the h3′UTRome library comprises 1,461 human 3′UTRs cloned into Gateway® entry vectors, ready for downstream analyses. It contains 3′UTRs for 985 transcription factors, 156 kinases, 171 RNA binding proteins, and 186 other genes involved in gene regulation and in disease. We demonstrate the feasibility of the h3′UTRome library by screening a panel of 87 3′UTRs for targeting by two miRNAs: let-7c, which is implicated in tumorigenesis, and miR-221, which is implicated in atherosclerosis and heart disease. The panel is enriched with genes involved in the RAS signaling pathway, putative novel targets for the two miRNAs, as well as genes implicated in tumorigenesis and heart disease.ConclusionsThe h3′UTRome v1 library is a modular resource that can be utilized for high-throughput screens to identify regulatory interactions between trans-acting factors and 3′UTRs, Importantly, the library can be customized based on the specifications of the researcher, allowing the systematic study of human 3′UTR biology.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2238-1) contains supplementary material, which is available to authorized users.

An Efficient Compression Algorithm for Forthcoming New Species

Genomic repositories gradually increase individual and reference sequences, which shares long identical and near-identical strings of nucleotides. In this paper a lossless DNA data compression technique called Optimized Base Repeat Length DNA Compression (OBRLDNAComp) has been proposed, based upon redundancy of DNA sequences. For easy storage, retrieval time reducing and to find similarity within and between sequences compression is mandatory. OBRLDNAComp searches long identical and near-identical strings of nucleotides which are overlooked by other DNA specific compression algorithms. This technique is an optimal solution of longest possible exact repeat benefits towards compression ratio. It scans a sequence horizontally from left to right to find statistic of repeats then follow substitution technique to compress those repeats. The algorithm is straightforward and does not need any external reference file; it scans the individual file for compression and decompression. The achieved compression ratio 1.673 bpb outperforms many non-reference based compression methods.

Standards for Clinical Grade Genomic Databases.

Next-generation sequencing performed in a clinical environment must meet clinical standards, which requires reproducibility of all aspects of the testing. Clinical-grade genomic databases (CGGDs) are required to classify a variant and to assist in the professional interpretation of clinical next-generation sequencing. Applying quality laboratory standards to the reference databases used for sequence-variant interpretation presents a new challenge for validation and curation. To define CGGD and the categories of information contained in CGGDs and to frame recommendations for the structure and use of these databases in clinical patient care. Members of the College of American Pathologists Personalized Health Care Committee reviewed the literature and existing state of genomic databases and developed a framework for guiding CGGD development in the future. Clinical-grade genomic databases may provide different types of information. This work group defined 3 layers of information in CGGDs: clinical genomic variant repositories, genomic medical data repositories, and genomic medicine evidence databases. The layers are differentiated by the types of genomic and medical information contained and the utility in assisting with clinical interpretation of genomic variants. Clinical-grade genomic databases must meet specific standards regarding submission, curation, and retrieval of data, as well as the maintenance of privacy and security. These organizing principles for CGGDs should serve as a foundation for future development of specific standards that support the use of such databases for patient care.

National Database for Autism Research (NDAR): Big Data Opportunities for Health Services Research and Health Technology Assessment.

The National Database for Autism Research (NDAR) is a US National Institutes of Health (NIH)-funded research data repository created by integrating heterogeneous datasets through data sharing agreements between autism researchers and the NIH. To date, NDAR is considered the largest neuroscience and genomic data repository for autism research. In addition to biomedical data, NDAR contains a large collection of clinical and behavioral assessments and health outcomes from novel interventions. Importantly, NDAR has a global unique patient identifier that can be linked to aggregated individual-level data for hypothesis generation and testing, and for replicating research findings. As such, NDAR promotes collaboration and maximizes public investment in the original data collection. As screening and diagnostic technologies as well as interventions for children with autism are expensive, health services research (HSR) and health technology assessment (HTA) are needed to generate more evidence to facilitate implementation when warranted. This article describes NDAR and explains its value to health services researchers and decision scientists interested in autism and other mental health conditions. We provide a description of the scope and structure of NDAR and illustrate how data are likely to grow over time and become available for HSR and HTA.