Publications by authors named "Chris Zaleski"

10 Publications

  • Page 1 of 1

A limited set of transcriptional programs define major cell types.

Genome Res 2020 07 29;30(7):1047-1059. Epub 2020 Jul 29.

Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, E-08003 Barcelona, Catalonia, Spain.

We have produced RNA sequencing data for 53 primary cells from different locations in the human body. The clustering of these primary cells reveals that most cells in the human body share a few broad transcriptional programs, which define five major cell types: epithelial, endothelial, mesenchymal, neural, and blood cells. These act as basic components of many tissues and organs. Based on gene expression, these cell types redefine the basic histological types by which tissues have been traditionally classified. We identified genes whose expression is specific to these cell types, and from these genes, we estimated the contribution of the major cell types to the composition of human tissues. We found this cellular composition to be a characteristic signature of tissues and to reflect tissue morphological heterogeneity and histology. We identified changes in cellular composition in different tissues associated with age and sex, and found that departures from the normal cellular composition correlate with histological phenotypes associated with disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/gr.263186.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397875PMC
July 2020

Dynamics of microRNA expression during mouse prenatal development.

Genome Res 2019 11 23;29(11):1900-1909. Epub 2019 Oct 23.

Department of Developmental and Cell Biology, University of California Irvine, Irvine, California 92697, USA.

MicroRNAs (miRNAs) play a critical role as posttranscriptional regulators of gene expression. The ENCODE Project profiled the expression of miRNAs in an extensive set of organs during a time-course of mouse embryonic development and captured the expression dynamics of 785 miRNAs. We found distinct organ-specific and developmental stage-specific miRNA expression clusters, with an overall pattern of increasing organ-specific expression as embryonic development proceeds. Comparative analysis of conserved miRNAs in mouse and human revealed stronger clustering of expression patterns by organ type rather than by species. An analysis of messenger RNA expression clusters compared with miRNA expression clusters identifies the potential role of specific miRNA expression clusters in suppressing the expression of mRNAs specific to other developmental programs in the organ in which these miRNAs are expressed during embryonic development. Our results provide the most comprehensive time-course of miRNA expression as part of an integrated ENCODE reference data set for mouse embryonic development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/gr.248997.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836743PMC
November 2019

Enhanced transcriptome maps from multiple mouse tissues reveal evolutionary constraint in gene expression.

Nat Commun 2015 Jan 13;6:5903. Epub 2015 Jan 13.

Functional Genomics Group, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.

Mice have been a long-standing model for human biology and disease. Here we characterize, by RNA sequencing, the transcriptional profiles of a large and heterogeneous collection of mouse tissues, augmenting the mouse transcriptome with thousands of novel transcript candidates. Comparison with transcriptome profiles in human cell lines reveals substantial conservation of transcriptional programmes, and uncovers a distinct class of genes with levels of expression that have been constrained early in vertebrate evolution. This core set of genes captures a substantial fraction of the transcriptional output of mammalian cells, and participates in basic functional and structural housekeeping processes common to all cell types. Perturbation of these constrained genes is associated with significant phenotypes including embryonic lethality and cancer. Evolutionary constraint in gene expression levels is not reflected in the conservation of the genomic sequences, but is associated with conserved epigenetic marking, as well as with characteristic post-transcriptional regulatory programme, in which sub-cellular localization and alternative splicing play comparatively large roles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncomms6903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308717PMC
January 2015

A comparative encyclopedia of DNA elements in the mouse genome.

Nature 2014 Nov;515(7527):355-64

Bioinformatics and Genomics, Centre for Genomic Regulation (CRG) and UPF, Doctor Aiguader, 88, 08003 Barcelona, Catalonia, Spain.

The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature13992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266106PMC
November 2014

Comparative analysis of the transcriptome across distant species.

Nature 2014 Aug;512(7515):445-8

Functional Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature13424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155737PMC
August 2014

STAR: ultrafast universal RNA-seq aligner.

Bioinformatics 2013 Jan 25;29(1):15-21. Epub 2012 Oct 25.

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.

Motivation: Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases.

Results: To align our large (>80 billon reads) ENCODE Transcriptome RNA-seq dataset, we developed the Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. STAR outperforms other aligners by a factor of >50 in mapping speed, aligning to the human genome 550 million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions, STAR can discover non-canonical splices and chimeric (fusion) transcripts, and is also capable of mapping full-length RNA sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons, we experimentally validated 1960 novel intergenic splice junctions with an 80-90% success rate, corroborating the high precision of the STAR mapping strategy.

Availability And Implementation: STAR is implemented as a standalone C++ code. STAR is free open source software distributed under GPLv3 license and can be downloaded from http://code.google.com/p/rna-star/.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/bts635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530905PMC
January 2013

Landscape of transcription in human cells.

Nature 2012 Sep;489(7414):101-8

Centre for Genomic Regulation and UPF, Doctor Aiguader 88, Barcelona 08003, Catalonia, Spain.

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature11233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684276PMC
September 2012

An encyclopedia of mouse DNA elements (Mouse ENCODE).

Genome Biol 2012 Aug 13;13(8):418. Epub 2012 Aug 13.

To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/gb-2012-13-8-418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491367PMC
August 2012

The developmental transcriptome of Drosophila melanogaster.

Nature 2011 Mar 22;471(7339):473-9. Epub 2010 Dec 22.

Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut 06030-6403, USA.

Drosophila melanogaster is one of the most well studied genetic model organisms; nonetheless, its genome still contains unannotated coding and non-coding genes, transcripts, exons and RNA editing sites. Full discovery and annotation are pre-requisites for understanding how the regulation of transcription, splicing and RNA editing directs the development of this complex organism. Here we used RNA-Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct developmental stages. We identified 111,195 new elements, including thousands of genes, coding and non-coding transcripts, exons, splicing and editing events, and inferred protein isoforms that previously eluded discovery using established experimental, prediction and conservation-based approaches. These data substantially expand the number of known transcribed elements in the Drosophila genome and provide a high-resolution view of transcriptome dynamics throughout development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature09715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075879PMC
March 2011

The transcriptional diversity of 25 Drosophila cell lines.

Genome Res 2011 Feb 22;21(2):301-14. Epub 2010 Dec 22.

Center for Genomics and Bioinformatics, Indiana University, Bloomington, Indiana 47405, USA.

Drosophila melanogaster cell lines are important resources for cell biologists. Here, we catalog the expression of exons, genes, and unannotated transcriptional signals for 25 lines. Unannotated transcription is substantial (typically 19% of euchromatic signal). Conservatively, we identify 1405 novel transcribed regions; 684 of these appear to be new exons of neighboring, often distant, genes. Sixty-four percent of genes are expressed detectably in at least one line, but only 21% are detected in all lines. Each cell line expresses, on average, 5885 genes, including a common set of 3109. Expression levels vary over several orders of magnitude. Major signaling pathways are well represented: most differentiation pathways are "off" and survival/growth pathways "on." Roughly 50% of the genes expressed by each line are not part of the common set, and these show considerable individuality. Thirty-one percent are expressed at a higher level in at least one cell line than in any single developmental stage, suggesting that each line is enriched for genes characteristic of small sets of cells. Most remarkable is that imaginal disc-derived lines can generally be assigned, on the basis of expression, to small territories within developing discs. These mappings reveal unexpected stability of even fine-grained spatial determination. No two cell lines show identical transcription factor expression. We conclude that each line has retained features of an individual founder cell superimposed on a common "cell line" gene expression pattern.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/gr.112961.110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032933PMC
February 2011
-->