Publications by authors named "Drew T Erickson"

9 Publications

  • Page 1 of 1

Ontology application and use at the ENCODE DCC.

Database (Oxford) 2015 16;2015. Epub 2015 Mar 16.

Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA and Center for Biomolecular Science and Engineering, School of Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA

The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a catalog of genomic annotations. To date, the project has generated over 4000 experiments across more than 350 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory network and transcriptional landscape of the Homo sapiens and Mus musculus genomes. All ENCODE experimental data, metadata and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage and distribution to community resources and the scientific community. As the volume of data increases, the organization of experimental details becomes increasingly complicated and demands careful curation to identify related experiments. Here, we describe the ENCODE DCC's use of ontologies to standardize experimental metadata. We discuss how ontologies, when used to annotate metadata, provide improved searching capabilities and facilitate the ability to find connections within a set of experiments. Additionally, we provide examples of how ontologies are used to annotate ENCODE metadata and how the annotations can be identified via ontology-driven searches at the ENCODE portal. As genomic datasets grow larger and more interconnected, standardization of metadata becomes increasingly vital to allow for exploration and comparison of data between different scientific projects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/database/bav010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360730PMC
September 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

Decomposing effects of time on task reveals an anteroposterior gradient of perceptual decision regions.

PLoS One 2013 19;8(8):e72074. Epub 2013 Aug 19.

Department of Psychology, University of Toronto, Toronto, Ontario, Canada.

In perceptual decision making, the selection of an appropriate action depends critically on an organism's ability to use sensory inputs to accumulate evidence for a decision. However, differentiating decision-related processes from effects of "time on task" can be difficult. Here we combine the response signal paradigm, in which the experimenter rather than the subject dictates the time of the response, and independent components analysis (ICA) to search for signatures consistent with time on task and decision making, respectively, throughout the brain. Using this novel approach, we identify two such independent components from BOLD activity related to a random dot motion task: one sensitive to the main effect of stimulus duration, and one to both the main effect of motion coherence and its interaction with duration. Furthermore, we demonstrate that these two components are expressed differently throughout the brain, with activity in occipital regions most reflective of the former, activity within intraparietal sulcus modulated by both factors, and more anterior regions including the anterior insula, pre-SMA, and inferior frontal sulcus driven almost exclusively by the latter. Consistent with these ICA findings, cluster analysis identifies a posterior-to-anterior gradient that differentiates regions sensitive to time on task from regions whose activity is strongly tied to motion coherence. Together, these findings demonstrate that progressively more anterior regions are likely to participate in progressively more proximate decision-related processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072074PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747156PMC
April 2014

The neural representation of sensorimotor transformations in a human perceptual decision making network.

Neuroimage 2013 Oct 28;79:340-50. Epub 2013 Apr 28.

Department of Neurology, University of California, San Francisco, CA 94608, USA.

Humans can quickly engage a neural network to transform complex visual stimuli into a motor response. Activity from a key region within this network, the intraparietal sulcus (IPS), has been associated with evidence accumulation and motor planning, thus implicating it in sensorimotor transformations. If such transformations occur within a brain region, a key and untested prediction is that neural activity reflecting both the parametric amount of evidence available and the timing of motor planning can be independently manipulated. To investigate these ideas, we constructed a dot motion discrimination task in which information about response modality (what to use) and response mapping (how to use it) was provided independently either before or after presentation of a dot motion coherence stimulus whose strength varied across trials. Consistent with our hypothesis, activity within IPS covaried with dot motion coherence during the stimulus phase, and as information necessary for the response was delayed, the peak of IPS activity shifted to the response phase. In contrast, areas such as the motion-sensitive region MT+ and the supplementary motor area demonstrated activity limited to the stimulus and response phases of the task, respectively. These results show that activity in IPS correlates with temporally dissociable representations consistent with both evidence accumulation and motor planning, and suggest that IPS is a core component for sensorimotor transformations within the perceptual decision-making network.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2013.04.085DOI Listing
October 2013

Neural representations of relevant and irrelevant features in perceptual decision making.

J Neurosci 2010 Nov;30(47):15778-89

Department of Neurology, University of California, San Francisco, Emeryville, CA 94608, USA.

Although perceptual decision making activates a network of brain areas involved in sensory, integrative, and motor functions, circuit activity can clearly be modulated by factors beyond the stimulus. Of particular interest is to understand how the network is modulated by top-down factors such as attention. Here, we demonstrate in a motion coherence task that selective attention produces marked changes in the blood oxygen level-dependent (BOLD) response in a subset of regions within a human perceptual decision-making circuit. Specifically, when motion is attended, the BOLD response decreases with increasing motion coherence in many regions, including the motion-sensitive area MT+, the intraparietal sulcus, and the inferior frontal sulcus. However, when motion is ignored, the negative parametric response in a subset of this circuit becomes positive. Through both modeling and connectivity analyses, we demonstrate that this inversion both reflects a top-down influence and segregates attentional from accumulation regions, thereby permitting us to further delineate the contributions of different regions to the perceptual decision.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.3163-10.2010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020592PMC
November 2010

Predicting phenotype from genotype: normal pigmentation.

J Forensic Sci 2010 Mar 11;55(2):315-22. Epub 2010 Feb 11.

Department of Pediatrics, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.

Genetic information in forensic studies is largely limited to CODIS data and the ability to match samples and assign them to an individual. However, there are circumstances, in which a given DNA sample does not match anyone in the CODIS database, and no other information about the donor is available. In this study, we determined 75 SNPs in 24 genes (previously implicated in human or animal pigmentation studies) for the analysis of single- and multi-locus associations with hair, skin, and eye color in 789 individuals of various ethnic backgrounds. Using multiple linear regression modeling, five SNPs in five genes were found to account for large proportions of pigmentation variation in hair, skin, and eyes in our across-population analyses. Thus, these models may be of predictive value to determine an individual's pigmentation type from a forensic sample, independent of ethnic origin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1556-4029.2009.01317.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626268PMC
March 2010

The functional anatomy of a perceptual decision in the human brain.

J Neurophysiol 2010 Mar 23;103(3):1179-94. Epub 2009 Dec 23.

Helen Wills Neuroscience Institute, 132 Barker Hall, University of California at Berkeley, Berkeley, CA 94720, USA.

Our ability to make rapid decisions based on sensory information belies the complexity of the underlying computations. Recently, "accumulator" models of decision making have been shown to explain the activity of parietal neurons as macaques make judgments concerning visual motion. Unraveling the operation of a decision-making circuit, however, involves understanding both the responses of individual components in the neural circuitry and the relationships between them. In this functional magnetic resonance imaging study of the decision process in humans, we demonstrate that an accumulator model predicts responses to visual motion in the intraparietal sulcus (IPS). Significantly, the metrics used to define responses within the IPS also reveal distinct but interacting nodes in a circuit, including early sensory detectors in visual cortex, the visuomotor integration system of the IPS, and centers of cognitive control in the prefrontal cortex, all of which collectively define a perceptual decision-making network.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/jn.00364.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887630PMC
March 2010

Stem cell transplantation demonstrates that Sox6 represses epsilon y globin expression in definitive erythropoiesis of adult mice.

Exp Hematol 2007 Mar;35(3):358-67

Department of Pediatrics, University of Arizona, College of Medicine, Tucson, AZ 85724, USA.

Sox6, a member of the Sox transcription factor family, is essential for the silencing of epsilon y globin gene expression in definitive erythropoiesis of mice. Homozygous Sox6-null mice are neonatally lethal, precluding analysis at later stages. We created adult mice that are deficient in Sox6 specifically in hematopoietic tissues by transplanting embryonic liver stem cells from Sox6-deficient mice into lethally irradiated congenic wild-type adult mice. The mice receiving mutant stem cells (mutant engrafted) showed high expression levels of epsilon y in bone marrow, spleen, and circulating blood compared with mice receiving wild-type and heterozygous stem cells (control engrafted). The level of expression of epsilon y in circulating blood was directly correlated with the percentage of successful mutant donor cell engraftment. Additionally, the mutant engrafted adult mice showed an increase in erythroid precursor cells in bone marrow, spleen, and blood. Thus, Sox6 continues to function as a major regulator of epsilon y in adult definitive erythropoiesis and is required for normal erythrocyte maturation. Therefore, Sox6 may provide a novel therapeutic target by reactivating epsilon y in patients with hemoglobinopathies such as sickle cell anemia and beta-thalassemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exphem.2006.11.009DOI Listing
March 2007

Sox6 directly silences epsilon globin expression in definitive erythropoiesis.

PLoS Genet 2006 Feb 3;2(2):e14. Epub 2006 Feb 3.

Department of Pediatrics, University of Arizona, College of Medicine, Tucson, Arizona, USA.

Sox6 is a member of the Sox transcription factor family that is defined by the conserved high mobility group (HMG) DNA binding domain, first described in the testis determining gene, Sry. Previous studies have suggested that Sox6 plays a role in the development of the central nervous system, cartilage, and muscle. In the Sox6-deficient mouse, p100H, epsilony globin is persistently expressed, and increased numbers of nucleated red cells are present in the fetal circulation. Transfection assays in GM979 (erythroleukemic) cells define a 36-base pair region of the epsilony proximal promoter that is critical for Sox6 mediated repression. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrate that Sox6 acts as a repressor by directly binding to the epsilony promoter. The normal expression of Sox6 in wild-type fetal liver and the ectopic expression of epsilony in p100H homozygous fetal liver demonstrate that Sox6 functions in definitive erythropoiesis. The present study shows that Sox6 is required for silencing of epsilony globin in definitive erythropoiesis and suggests a role for Sox6 in erythroid cell maturation. Thus, Sox6 regulation of epsilony globin might provide a novel therapeutical target in the treatment of hemoglobinopathies such as sickle cell anemia and thalassemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.0020014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1359074PMC
February 2006