Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation

O’Leary, Nuala; Wright, Mathew W.; Brister, J. Rodney; Ciufo, Stacy; Haddad, Diana; McVeigh, Richard; Rajput, Bhanu; Robbertse, Barbara; Smith-White, Brian; Ako-adjei, Danso; Astashyn, Alexander; Badretdin, Azat; Bào, Yīmíng; Blinkova, Olga; Brover, Vyacheslav; Chetvernin, Vyacheslav; Choi, Jinna; Cox, Eric; Ermolaeva, Olga; Farrell, Catherine; Goldfarb, Tamara; Gupta, Tripti; Haft, Daniel H.; Hatcher, Eneida L.; Hlavina, Wratko; Joardar, Vinita; Kodali, Vamsi K.; Li, Wenjun; Maglott, Donna; Masterson, Patrick; McGarvey, Kelly M.; Murphy, Michael R.; O’Neill, Kathleen; Pujar, Shashikant; Rangwala, Sanjida H; Rausch, Daniel; Riddick, Lillian D.; Schoch, Conrad L.; Shkeda, Andrei; Storz, Susan S.; Sun, Hanzhen; Thibaud‐Nissen, Françoise; Tolstoy, Igor; Tully, Raymond E.; Vatsan, Anjana Raina; Wallin, Craig; Webb, David; Wu, Wendy; Landrum, Melissa; Kimchi, Avi; Tatusova, Tatiana; DiCuccio, Michael; Kitts, Paul; Pruitt, Kim D.

doi:10.1093/nar/gkv1189

Cited by 5,221 publications

(4,520 citation statements)

References 66 publications

Supporting

Mentioning

4,246

Contrasting

Unclassified

Order By: Relevance

“…1; Table 2). Because the transcript content of these two annotation releases was not identical and may contribute to observed differences in the annotation statistics, we also aligned two large public annotation sets (GENCODE23 [basic] and RefSeq71) to the GRCh37 and GRCh38 full assemblies to gauge the impact of improvements on gene representation (Harrow et al 2012;O'Leary et al 2016). Similar to the previously described comparison, in GRCh38 we find that both annotation sets show increases in overall transcript alignments with a substantial decrease in split and low quality transcript alignments (Table 3; Supplemental Worksheet S1).…”

Section: Assembly Updatesmentioning

confidence: 99%

Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly

Graves-Lindsay²,

et al. 2017

Self Cite

View full text Add to dashboard Cite

The human reference genome assembly plays a central role in nearly all aspects of today's basic and clinical research. GRCh38 is the first coordinate-changing assembly update since 2009; it reflects the resolution of roughly 1000 issues and encompasses modifications ranging from thousands of single base changes to megabase-scale path reorganizations, gap closures, and localization of previously orphaned sequences. We developed a new approach to sequence generation for targeted base updates and used data from new genome mapping technologies and single haplotype resources to identify and resolve larger assembly issues. For the first time, the reference assembly contains sequence-based representations for the centromeres. We also expanded the number of alternate loci to create a reference that provides a more robust representation of human population variation. We demonstrate that the updates render the reference an improved annotation substrate, alter read alignments in unchanged regions, and impact variant interpretation at clinically relevant loci. We additionally evaluated a collection of new de novo long-read haploid assemblies and conclude that although the new assemblies compare favorably to the reference with respect to continuity, error rate, and gene completeness, the reference still provides the best representation for complex genomic regions and coding sequences. We assert that the collected updates in GRCh38 make the newer assembly a more robust substrate for comprehensive analyses that will promote our understanding of human biology and advance our efforts to improve health.

show abstract

Section: Assembly Updatesmentioning

confidence: 99%

Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly

Graves-Lindsay²,

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…These polyspecific organic cation transporters in the liver, kidney, intestine, and other organs play critical roles in the elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. 30 This organic cation transporter 3 was also identified as one of the important risk loci for prostate cancer and is markedly under-expressed in aggressive prostate cancers. 31 …”

Section: Application To Metabochip Data For Lipid Traitsmentioning

confidence: 99%

Unified Sequence-Based Association Tests Allowing for Multiple Functional Annotations and Meta-analysis of Noncoding Variation in Metabochip Data

Lee

et al. 2017

The American Journal of Human Genetics

View full text Add to dashboard Cite

Substantial progress has been made in the functional annotation of genetic variation in the human genome. Integrative analysis that incorporates such functional annotations into sequencing studies can aid the discovery of disease-associated genetic variants, especially those with unknown function and located outside protein-coding regions. Direct incorporation of one functional annotation as weight in existing dispersion and burden tests can suffer substantial loss of power when the functional annotation is not predictive of the risk status of a variant. Here, we have developed unified tests that can utilize multiple functional annotations simultaneously for integrative association analysis with efficient computational techniques. We show that the proposed tests significantly improve power when variant risk status can be predicted by functional annotations. Importantly, when functional annotations are not predictive of risk status, the proposed tests incur only minimal loss of power in relation to existing dispersion and burden tests, and under certain circumstances they can even have improved power by learning a weight that better approximates the underlying disease model in a data-adaptive manner.The tests can be constructed with summary statistics of existing dispersion and burden tests for sequencing data, therefore allowing meta-analysis of multiple studies without sharing individual-level data. We applied the proposed tests to a meta-analysis of noncoding rare variants in Metabochip data on 12,281 individuals from eight studies for lipid traits. By incorporating the Eigen functional score, we detected significant associations between noncoding rare variants in SLC22A3 and low-density lipoprotein and total cholesterol, associations that are missed by standard dispersion and burden tests.

show abstract

“…We were aware that the primers for qRT‐PCR can amplify all three HOTAIR isoforms as listed in the latest RefSeq release 81 (Fig. 5B) (O'Leary et al ., 2016). Thus, induction of HOTAIR in lrECM 3D culture could result from the activation of a novel isoform other than HOTAIR‐C.…”

Section: Resultsmentioning

confidence: 99%

Induction of a novel isoform of the lncRNA HOTAIR in Claudin‐low breast cancer cells attached to extracellular matrix

Zhuang

et al. 2017

Molecular Oncology

View full text Add to dashboard Cite

Elevated overexpression of the lncRNA HOTAIR mediates invasion and metastasis in breast cancer. In an apparent paradox, we observed low expression of HOTAIR in the invasive Claudin‐low MDA‐MB‐231 and Hs578T cells in two‐dimensional culture (2D). However, HOTAIR expression exhibited robust induction in laminin‐rich extracellular matrix‐based three‐dimensional organotypic culture (lrECM 3D) over that in 2D culture. Induction of HOTAIR required intact ECM signaling, namely integrin α2 and SRC kinase activity. Moreover, invasive growth was suppressed by HOTAIR‐specific siRNA. Induction of HOTAIR in lrECM 3D culture resulted from the activation of a novel isoform of HOTAIR (HOTAIR‐N) whose transcription is started from the first intron of the HOXC11 gene. The HOTAIR‐N promoter exhibited increased trimethylation of histone H3 lysine 4, a histone marker of active transcription, and binding of BRD4, a reader of transcriptionally active histone markers. Inhibition of BRD4 substantially reduced the expression of HOTAIR in lrECM 3D culture. In summary, our results indicate that HOTAIR expression is activated by BRD4 binding to a novel HOTAIR‐N promoter in Claudin‐low breast cancer cells that are attached to ECM. Induction of HOTAIR is required for invasive growth of Claudin‐low breast cancer cells in lrECM 3D culture.

show abstract

Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation

Cited by 5,221 publications

References 66 publications

Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly

Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly

Unified Sequence-Based Association Tests Allowing for Multiple Functional Annotations and Meta-analysis of Noncoding Variation in Metabochip Data

Induction of a novel isoform of the lncRNA HOTAIR in Claudin‐low breast cancer cells attached to extracellular matrix

Contact Info

Product

Resources

About