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Publications

Publications by LIAAD

2015

Some notes and comments on the efficient use of information in repeated games with Poisson signals

Authors
Osório, A;

Publication
Operations Research Letters

Abstract
In the present paper we characterize the optimal use of Poisson signals to establish incentives in the "bad" and "good" news models of Abreu et al. (1991). In the former, for small time intervals the signals' quality is high and we observe a "selective" use of information; otherwise there is a "mass" use. In the latter, for small time intervals the signals' quality is low and we observe a "fine" use of information; otherwise there is a "non-selective" use.

2015

Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases

Authors
Yang J.; Huang T.; Petralia F.; Long Q.; Zhang B.; Argmann C.; Zhao Y.; Mobbs C.V.; Schadt E.E.; Zhu J.; Tu Z.; Ardlie K.G.; Deluca D.S.; Segrè A.V.; Sullivan T.J.; Young T.R.; Gelfand E.T.; Trowbridge C.A.; Maller J.B.; Tukiainen T.; Lek M.; Ward L.D.; Kheradpour P.; Iriarte B.; Meng Y.; Palmer C.D.; Winckler W.; Hirschhorn J.; Kellis M.; MacArthur D.G.; Getz G.; Shablin A.A.; Li G.; Zhou Y.H.; Nobel A.B.; Rusyn I.; Wright F.A.; Lappalainen T.; Ferreira P.G.; Ongen H.; Rivas M.A.; Battle A.; Mostafavi S.; Monlong J.; Sammeth M.; Mele M.; Reverter F.; Goldman J.; Koller D.; Guigo R.; McCarthy M.I.; Dermitzakis E.T.; Gamazon E.R.; Konkashbaev A.; Nicolae D.L.; Cox N.J.; Flutre T.; Wen X.; Stephens M.; Pritchard J.K.; Lin L.; Liu J.; Brown A.; Mestichelli B.; Tidwell D.; Lo E.; Salvatore M.; Shad S.; Thomas J.A.; Lonsdale J.T.; Choi C.; Karasik E.; Ramsey K.; Moser M.T.; Foster B.A.; Gillard B.M.; Syron J.; Fleming J.; Magazine H.; Hasz R.; Walters G.D.; Bridge J.P.; Miklos M.; Sullivan S.; Barker L.K.; Traino H.; Mosavel M.; Siminoff L.A.; Valley D.R.; Rohrer D.C.; Jewel S.; Branton P.; Sobin L.H.; Qi L.; Hariharan P.; Wu S.; Tabor D.; Shive C.; Smith A.M.; Buia S.A.;

Publication
Scientific Reports

Abstract
Aging is one of the most important biological processes and is a known risk factor for many age-related diseases in human. Studying age-related transcriptomic changes in tissues across the whole body can provide valuable information for a holistic understanding of this fundamental process. In this work, we catalogue age-related gene expression changes in nine tissues from nearly two hundred individuals collected by the Genotype-Tissue Expression (GTEx) project. In general, we find the aging gene expression signatures are very tissue specific. However, enrichment for some well-known aging components such as mitochondria biology is observed in many tissues. Different levels of cross-tissue synchronization of age-related gene expression changes are observed, and some essential tissues (e.g., heart and lung) show much stronger "co-aging" than other tissues based on a principal component analysis. The aging gene signatures and complex disease genes show a complex overlapping pattern and only in some cases, we see that they are significantly overlapped in the tissues affected by the corresponding diseases. In summary, our analyses provide novel insights to the co-regulation of age-related gene expression in multiple tissues; it also presents a tissue-specific view of the link between aging and age-related diseases.

2015

Biased allelic expression in human primary fibroblast single cells

Authors
Borel, C; Ferreira, PG; Santoni, F; Delaneau, O; Fort, A; Popadin, KY; Garieri, M; Falconnet, E; Ribaux, P; Guipponi, M; Padioleau, I; Carninci, P; Dermitzakis, ET; Antonarakis, SE;

Publication
American Journal of Human Genetics

Abstract
The study of gene expression in mammalian single cells via genomic technologies now provides the possibility to investigate the patterns of allelic gene expression. We used single-cell RNA sequencing to detect the allele-specific mRNA level in 203 single human primary fibroblasts over 133,633 unique heterozygous single-nucleotide variants (hetSNVs). We observed that at the snapshot of analyses, each cell contained mostly transcripts from one allele from the majority of genes; indeed, 76.4% of the hetSNVs displayed stochastic monoallelic expression in single cells. Remarkably, adjacent hetSNVs exhibited a haplotype-consistent allelic ratio; in contrast, distant sites located in two different genes were independent of the haplotype structure. Moreover, the allele-specific expression in single cells correlated with the abundance of the cellular transcript. We observed that genes expressing both alleles in the majority of the single cells at a given time point were rare and enriched with highly expressed genes. The relative abundance of each allele in a cell was controlled by some regulatory mechanisms given that we observed related single-cell allelic profiles according to genes. Overall, these results have direct implications in cellular phenotypic variability. © 2015 The American Society of Human Genetics.

2015

Erratum: Short term exposure of beta cells to low concentrations of interleukin-1ß improves insulin secretion through focal adhesion and actin remodeling and regulation of gene expression (Journal of Biological Chemistr (2015) 290 (6653-6669))

Authors
Arous, C; Ferreira, PG; Dermitzakis, ET; Halban, PA;

Publication
Journal of Biological Chemistry

Abstract

2015

The human transcriptome across tissues and individuals

Authors
Melé, M; Ferreira, PG; Reverter, F; DeLuca, DS; Monlong, J; Sammeth, M; Young, TR; Goldmann, JM; Pervouchine, DD; Sullivan, TJ; Johnson, R; Segrè, AV; Djebali, S; Niarchou, A; Wright, FA; Lappalainen, T; Calvo, M; Getz, G; Dermitzakis, ET; Ardlie, KG; Guigó, R;

Publication
Science

Abstract
Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used RNA sequence data generated by Genotype-Tissue Expression (GTEx) project to investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples. These signatures are dominated by a relatively small number of genes - which is most clearly seen in blood - though few are exclusive to a particular tissue and vary more across tissues than individuals. Genes exhibiting high interindividual expression variation include disease candidates associated with sex, ethnicity, and age. Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program. Variation in splicing, despite its stochasticity, may play in contrast a comparatively greater role in defining individual phenotypes.

2015

The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans

Authors
Ardlie, KG; DeLuca, DS; Segrè, AV; Sullivan, TJ; Young, TR; Gelfand, ET; Trowbridge, CA; Maller, JB; Tukiainen, T; Lek, M; Ward, LD; Kheradpour, P; Iriarte, B; Meng, Y; Palmer, CD; Esko, T; Winckler, W; Hirschhorn, JN; Kellis, M; MacArthur, DG; Getz, G; Shabalin, AA; Li, G; Zhou, YH; Nobel, AB; Rusyn, I; Wright, FA; Lappalainen, T; Ferreira, PG; Ongen, H; Rivas, MA; Battle, A; Mostafavi, S; Monlong, J; Sammeth, M; Melé, M; Reverter, F; Goldmann, JM; Koller, D; Guigó, R; McCarthy, MI; Dermitzakis, ET; Gamazon, ER; Im, HK; Konkashbaev, A; Nicolae, DL; Cox, NJ; Flutre, T; Wen, X; Stephens, M; Pritchard, JK; Tu, Z; Zhang, B; Huang, T; Long, Q; Lin, L; Yang, J; Zhu, J; Liu, J; Brown, A; Mestichelli, B; Tidwell, D; Lo, E; Salvatore, M; Shad, S; Thomas, JA; Lonsdale, JT; Moser, MT; Gillard, BM; Karasik, E; Ramsey, K; Choi, C; Foster, BA; Syron, J; Fleming, J; Magazine, H; Hasz, R; Walters, GD; Bridge, JP; Miklos, M; Sullivan, S; Barker, LK; Traino, HM; Mosavel, M; Siminoff, LA; Valley, DR; Rohrer, DC; Jewell, SD; Branton, PA; Sobin, LH; Barcus, M; Qi, L; McLean, J; Hariharan, P; Um, KS; Wu, S; Tabor, D; Shive, C; Smith, AM; Buia, SA; Undale, AH; Robinson, KL; Roche, N; Valentino, KM; Britton, A; Burges, R; Bradbury, D; Hambright, KW; Seleski, J; Korzeniewski, GE; Erickson, K; Marcus, Y; Tejada, J; Taherian, M; Lu, C; Basile, M; Mash, DC; Volpi, S; Struewing, JP; Temple, GF; Boyer, J; Colantuoni, D; Little, R; Koester, S; Carithers, LJ; Moore, HM; Guan, P; Compton, C; Sawyer, SJ; Demchok, JP; Vaught, JB; Rabiner, CA; Lockhart,;

Publication
Science

Abstract
Understanding the functional consequences of genetic variation, and how it affects complex human disease and quantitative traits, remains a critical challenge for biomedicine. We present an analysis of RNA sequencing data from 1641 samples across 43 tissues from 175 individuals, generated as part of the pilot phase of the Genotype-Tissue Expression (GTEx) project. We describe the landscape of gene expression across tissues, catalog thousands of tissue-specific and shared regulatory expression quantitative trait loci (eQTL) variants, describe complex network relationships, and identify signals from genome-wide association studies explained by eQTLs. These findings provide a systematic understanding of the cellular and biological consequences of human genetic variation and of the heterogeneity of such effects among a diverse set of human tissues.

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