Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 69

Publication Record

Connections

End Sequence Analysis Toolkit (ESAT) expands the extractable information from single-cell RNA-seq data.
Derr A, Yang C, Zilionis R, Sergushichev A, Blodgett DM, Redick S, Bortell R, Luban J, Harlan DM, Kadener S, Greiner DL, Klein A, Artyomov MN, Garber M
(2016) Genome Res 26: 1397-1410
MeSH Terms: Animals, Cells, Cultured, Dendritic Cells, Gene Library, Islets of Langerhans, Microfluidics, Rats, Sequence Analysis, RNA, Single-Cell Analysis, Transcriptome
Show Abstract · Added October 12, 2016
RNA-seq protocols that focus on transcript termini are well suited for applications in which template quantity is limiting. Here we show that, when applied to end-sequencing data, analytical methods designed for global RNA-seq produce computational artifacts. To remedy this, we created the End Sequence Analysis Toolkit (ESAT). As a test, we first compared end-sequencing and bulk RNA-seq using RNA from dendritic cells stimulated with lipopolysaccharide (LPS). As predicted by the telescripting model for transcriptional bursts, ESAT detected an LPS-stimulated shift to shorter 3'-isoforms that was not evident by conventional computational methods. Then, droplet-based microfluidics was used to generate 1000 cDNA libraries, each from an individual pancreatic islet cell. ESAT identified nine distinct cell types, three distinct β-cell types, and a complex interplay between hormone secretion and vascularization. ESAT, then, offers a much-needed and generally applicable computational pipeline for either bulk or single-cell RNA end-sequencing.
© 2016 Derr et al.; Published by Cold Spring Harbor Laboratory Press.
0 Communities
1 Members
0 Resources
10 MeSH Terms
Joint mouse-human phenome-wide association to test gene function and disease risk.
Wang X, Pandey AK, Mulligan MK, Williams EG, Mozhui K, Li Z, Jovaisaite V, Quarles LD, Xiao Z, Huang J, Capra JA, Chen Z, Taylor WL, Bastarache L, Niu X, Pollard KS, Ciobanu DC, Reznik AO, Tishkov AV, Zhulin IB, Peng J, Nelson SF, Denny JC, Auwerx J, Lu L, Williams RW
(2016) Nat Commun 7: 10464
MeSH Terms: Animals, Bone Density, Caenorhabditis elegans, Fumarate Hydratase, Gene Expression Regulation, Gene Library, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genomics, Humans, Mice, Mice, Inbred DBA, Quantitative Trait Loci
Show Abstract · Added April 29, 2016
Phenome-wide association is a novel reverse genetic strategy to analyze genome-to-phenome relations in human clinical cohorts. Here we test this approach using a large murine population segregating for ∼5 million sequence variants, and we compare our results to those extracted from a matched analysis of gene variants in a large human cohort. For the mouse cohort, we amassed a deep and broad open-access phenome consisting of ∼4,500 metabolic, physiological, pharmacological and behavioural traits, and more than 90 independent expression quantitative trait locus (QTL), transcriptome, proteome, metagenome and metabolome data sets--by far the largest coherent phenome for any experimental cohort (www.genenetwork.org). We tested downstream effects of subsets of variants and discovered several novel associations, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans, and missense mutations in Col6a5 that underlies variation in bone mineral density in both mouse and human.
1 Communities
2 Members
0 Resources
14 MeSH Terms
RNAseq by Total RNA Library Identifies Additional RNAs Compared to Poly(A) RNA Library.
Guo Y, Zhao S, Sheng Q, Guo M, Lehmann B, Pietenpol J, Samuels DC, Shyr Y
(2015) Biomed Res Int 2015: 862130
MeSH Terms: Gene Expression Profiling, Gene Library, Humans, Open Reading Frames, Poly A, RNA, RNA, Ribosomal, Sequence Analysis, RNA
Show Abstract · Added February 15, 2016
The most popular RNA library used for RNA sequencing is the poly(A) captured RNA library. This library captures RNA based on the presence of poly(A) tails at the 3' end. Another type of RNA library for RNA sequencing is the total RNA library which differs from the poly(A) library by capture method and price. The total RNA library costs more and its capture of RNA is not dependent on the presence of poly(A) tails. In practice, only ribosomal RNAs and small RNAs are washed out in the total RNA library preparation. To evaluate the ability of detecting RNA for both RNA libraries we designed a study using RNA sequencing data of the same two breast cancer cell lines from both RNA libraries. We found that the RNA expression values captured by both RNA libraries were highly correlated. However, the number of RNAs captured was significantly higher for the total RNA library. Furthermore, we identify several subsets of protein coding RNAs that were not captured efficiently by the poly(A) library. One of the most noticeable is the histone-encode genes, which lack the poly(A) tail.
1 Communities
3 Members
0 Resources
8 MeSH Terms
A Synthetic Lethal Screen Identifies DNA Repair Pathways that Sensitize Cancer Cells to Combined ATR Inhibition and Cisplatin Treatments.
Mohni KN, Thompson PS, Luzwick JW, Glick GG, Pendleton CS, Lehmann BD, Pietenpol JA, Cortez D
(2015) PLoS One 10: e0125482
MeSH Terms: Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Ataxia Telangiectasia Mutated Proteins, Cell Line, Tumor, Cell Survival, Cisplatin, DNA Repair, DNA-Directed DNA Polymerase, Drug Resistance, Neoplasm, Drug Synergism, Gene Library, HCT116 Cells, Humans, Intracellular Signaling Peptides and Proteins, Pyrazines, RNA, Small Interfering, Sulfones, Tumor Suppressor p53-Binding Protein 1
Show Abstract · Added February 4, 2016
The DNA damage response kinase ATR may be a useful cancer therapeutic target. ATR inhibition synergizes with loss of ERCC1, ATM, XRCC1 and DNA damaging chemotherapy agents. Clinical trials have begun using ATR inhibitors in combination with cisplatin. Here we report the first synthetic lethality screen with a combination treatment of an ATR inhibitor (ATRi) and cisplatin. Combination treatment with ATRi/cisplatin is synthetically lethal with loss of the TLS polymerase ζ and 53BP1. Other DNA repair pathways including homologous recombination and mismatch repair do not exhibit synthetic lethal interactions with ATRi/cisplatin, even though loss of some of these repair pathways sensitizes cells to cisplatin as a single-agent. We also report that ATRi strongly synergizes with PARP inhibition, even in homologous recombination-proficient backgrounds. Lastly, ATR inhibitors were able to resensitize cisplatin-resistant cell lines to cisplatin. These data provide a comprehensive analysis of DNA repair pathways that exhibit synthetic lethality with ATR inhibitors when combined with cisplatin chemotherapy, and will help guide patient selection strategies as ATR inhibitors progress into the cancer clinic.
1 Communities
2 Members
0 Resources
18 MeSH Terms
Three-stage quality control strategies for DNA re-sequencing data.
Guo Y, Ye F, Sheng Q, Clark T, Samuels DC
(2014) Brief Bioinform 15: 879-89
MeSH Terms: Computational Biology, DNA, Gene Library, High-Throughput Nucleotide Sequencing, Humans, Neoplasms, Polymorphism, Single Nucleotide, Quality Control, Sequence Alignment, Sequence Analysis, DNA
Show Abstract · Added December 12, 2013
Advances in next-generation sequencing (NGS) technologies have greatly improved our ability to detect genomic variants for biomedical research. In particular, NGS technologies have been recently applied with great success to the discovery of mutations associated with the growth of various tumours and in rare Mendelian diseases. The advance in NGS technologies has also created significant challenges in bioinformatics. One of the major challenges is quality control of the sequencing data. In this review, we discuss the proper quality control procedures and parameters for Illumina technology-based human DNA re-sequencing at three different stages of sequencing: raw data, alignment and variant calling. Monitoring quality control metrics at each of the three stages of NGS data provides unique and independent evaluations of data quality from differing perspectives. Properly conducting quality control protocols at all three stages and correctly interpreting the quality control results are crucial to ensure a successful and meaningful study.
© The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
0 Communities
1 Members
0 Resources
10 MeSH Terms
Powerful genetic resource for the study of methicillin-resistant Staphylococcus aureus.
Hammer ND, Skaar EP
(2013) MBio 4:
MeSH Terms: Gene Knockout Techniques, Gene Library, Genetics, Microbial, Humans, Methicillin-Resistant Staphylococcus aureus, Mutagenesis, Insertional
Show Abstract · Added February 11, 2016
In "A Genetic resource for Rapid and Comprehensive Phenotype Screening of Nonessential Staphylococcus aureus Genes" (mBio 4(2):e00537-12, doi: 10.1128/mBio.00537-12, 2013), Fey et al. describe the creation and application of a defined transposon mutant library of methicillin-resistant S. aureus. This library is well organized and made accessible to the research community through an easily navigable central repository. The mutant library promises to be a significant resource for researchers seeking a greater understanding of this pathogen.
0 Communities
1 Members
0 Resources
6 MeSH Terms
Transcriptome of the adult female malaria mosquito vector Anopheles albimanus.
Martínez-Barnetche J, Gómez-Barreto RE, Ovilla-Muñoz M, Téllez-Sosa J, García López DE, Dinglasan RR, Ubaida Mohien C, MacCallum RM, Redmond SN, Gibbons JG, Rokas A, Machado CA, Cazares-Raga FE, González-Cerón L, Hernández-Martínez S, Rodríguez López MH
(2012) BMC Genomics 13: 207
MeSH Terms: Animals, Anopheles, Chromosome Mapping, Databases, Genetic, Expressed Sequence Tags, Female, Gene Library, Genome, Host-Parasite Interactions, Insect Vectors, Plasmodium, Proteome, Sequence Analysis, DNA, Transcriptome
Show Abstract · Added August 16, 2012
BACKGROUND - Human Malaria is transmitted by mosquitoes of the genus Anopheles. Transmission is a complex phenomenon involving biological and environmental factors of humans, parasites and mosquitoes. Among more than 500 anopheline species, only a few species from different branches of the mosquito evolutionary tree transmit malaria, suggesting that their vectorial capacity has evolved independently. Anopheles albimanus (subgenus Nyssorhynchus) is an important malaria vector in the Americas. The divergence time between Anopheles gambiae, the main malaria vector in Africa, and the Neotropical vectors has been estimated to be 100 My. To better understand the biological basis of malaria transmission and to develop novel and effective means of vector control, there is a need to explore the mosquito biology beyond the An. gambiae complex.
RESULTS - We sequenced the transcriptome of the An. albimanus adult female. By combining Sanger, 454 and Illumina sequences from cDNA libraries derived from the midgut, cuticular fat body, dorsal vessel, salivary gland and whole body, we generated a single, high-quality assembly containing 16,669 transcripts, 92% of which mapped to the An. darlingi genome and covered 90% of the core eukaryotic genome. Bidirectional comparisons between the An. gambiae, An. darlingi and An. albimanus predicted proteomes allowed the identification of 3,772 putative orthologs. More than half of the transcripts had a match to proteins in other insect vectors and had an InterPro annotation. We identified several protein families that may be relevant to the study of Plasmodium-mosquito interaction. An open source transcript annotation browser called GDAV (Genome-Delinked Annotation Viewer) was developed to facilitate public access to the data generated by this and future transcriptome projects.
CONCLUSIONS - We have explored the adult female transcriptome of one important New World malaria vector, An. albimanus. We identified protein-coding transcripts involved in biological processes that may be relevant to the Plasmodium lifecycle and can serve as the starting point for searching targets for novel control strategies. Our data increase the available genomic information regarding An. albimanus several hundred-fold, and will facilitate molecular research in medical entomology, evolutionary biology, genomics and proteomics of anopheline mosquito vectors. The data reported in this manuscript is accessible to the community via the VectorBase website (http://www.vectorbase.org/Other/AdditionalOrganisms/).
1 Communities
0 Members
0 Resources
14 MeSH Terms
Identification and expression profiling of blood-brain barrier membrane proteins.
Agarwal N, Lippmann ES, Shusta EV
(2010) J Neurochem 112: 625-35
MeSH Terms: Animals, Blood-Brain Barrier, Cattle, Cell Line, Transformed, Cloning, Molecular, Endothelium, Vascular, Gene Expression Profiling, Gene Expression Regulation, Gene Library, Humans, Membrane Proteins, Microdissection, Microvessels, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, RNA, Messenger, Transfection
Show Abstract · Added August 19, 2015
Blood-brain barrier (BBB) membrane proteins play crucial roles in the proper functioning of the BBB as well as in disease progression. Previously, we developed a novel approach for identifying membrane proteins expressed at the BBB, which we referred to as multiplex expression cloning. In this study, the proteome coverage of the multiplex expression cloning approach was expanded to allow the identification of a total of 30 BBB membrane proteins that are diverse in function and abundance. To unveil those membrane proteins that are enriched at the BBB and hence partially responsible for some of its unique characteristics, the transcript abundance levels for all 30 BBB membrane proteins were compared with those found in microvessels derived from lung, liver, heart, and kidney. Such quantitative PCR profiling of RNA samples from laser capture microdissected microvessels revealed that the transcripts for five membrane proteins, namely Lutheran glycoprotein, carbonic anhydrase IV, uncoupling protein 2, podocalyxin, and solute carrier family 38, member 5, were BBB selective, in that expression was elevated in brain microvessels when compared with all of the vascular beds tested. Many other membrane protein transcripts, whereas not as BBB-restricted, showed selective expression within subsets of tissues indicating other potential parallels and contrasts between vascular beds in the body. The identification of BBB membrane proteins could help better understand the molecular mechanisms responsible for BBB function and those with selective expression may have utility for BBB-targeted therapies.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Hybrid selection of discrete genomic intervals on custom-designed microarrays for massively parallel sequencing.
Hodges E, Rooks M, Xuan Z, Bhattacharjee A, Benjamin Gordon D, Brizuela L, Richard McCombie W, Hannon GJ
(2009) Nat Protoc 4: 960-74
MeSH Terms: Animals, Base Sequence, DNA Primers, Gene Library, Genomics, Humans, Mice, Nucleic Acid Hybridization, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Sensitivity and Specificity, Sequence Analysis, DNA
Show Abstract · Added February 15, 2016
Complementary techniques that deepen information content and minimize reagent costs are required to realize the full potential of massively parallel sequencing. Here, we describe a resequencing approach that directs focus to genomic regions of high interest by combining hybridization-based purification of multi-megabase regions with sequencing on the Illumina Genome Analyzer (GA). The capture matrix is created by a microarray on which probes can be programmed as desired to target any non-repeat portion of the genome, while the method requires only a basic familiarity with microarray hybridization. We present a detailed protocol suitable for 1-2 microg of input genomic DNA and highlight key design tips in which high specificity (>65% of reads stem from enriched exons) and high sensitivity (98% targeted base pair coverage) can be achieved. We have successfully applied this to the enrichment of coding regions, in both human and mouse, ranging from 0.5 to 4 Mb in length. From genomic DNA library production to base-called sequences, this procedure takes approximately 9-10 d inclusive of array captures and one Illumina flow cell run.
0 Communities
1 Members
0 Resources
12 MeSH Terms
Quantitative exploration of the catalytic landscape separating divergent plant sesquiterpene synthases.
O'Maille PE, Malone A, Dellas N, Andes Hess B, Smentek L, Sheehan I, Greenhagen BT, Chappell J, Manning G, Noel JP
(2008) Nat Chem Biol 4: 617-23
MeSH Terms: Amino Acid Sequence, Carbon-Carbon Lyases, Catalysis, Evolution, Molecular, Gene Library, Hyoscyamus, Models, Molecular, Molecular Sequence Data, Molecular Structure, Mutagenesis, Phylogeny, Plant Extracts, Sequence Alignment, Tobacco
Show Abstract · Added February 15, 2016
Throughout molecular evolution, organisms create assorted chemicals in response to varying ecological niches. Catalytic landscapes underlie metabolic evolution, wherein mutational steps alter the biosynthetic properties of enzymes. Here we report the first systematic quantitative characterization of the catalytic landscape underlying the evolution of sesquiterpene chemical diversity. On the basis of our previous discovery of a set of nine naturally occurring amino acid substitutions that functionally interconverted orthologous sesquiterpene synthases from Nicotiana tabacum and Hyoscyamus muticus, we created a library of all possible residue combinations (2(9) = 512) in the N. tabacum enzyme. The product spectra of 418 active enzymes revealed a rugged landscape where several minimal combinations of the nine mutations encode convergent solutions to the interconversions of parental activities. Quantitative comparisons indicated context dependence for mutational effects--epistasis--in product specificity and promiscuity. These results provide a measure of the mutational accessibility of phenotypic variability in a diverging lineage of terpene synthases.
0 Communities
1 Members
0 Resources
14 MeSH Terms