Brent Pedersen

University of Colorado | UCD · Department of Medicine

The gain-of-function MUC5B promoter variant rs35705950 confers the largest risk, genetic or otherwise, for the development of idiopathic pulmonary fibrosis (IPF); however, the mechanisms underlying the regulation of MUC5B expression have yet to be elucidated. Here, we identify a critical regulatory domain that contains the MUC5B promoter variant an...

Background: Fibrotic idiopathic interstitial pneumonias (fIIP) are a group of fatal lung diseases with largely unknown etiology and without definitive treatment other than lung transplant to prolong life. There is strong evidence for the importance of both rare and common genetic risk alleles in familial and sporadic disease. We have previously us...

Rationale: Sequence variation, methylation differences, and transcriptional changes in Desmoplakin (DSP) have been observed in patients with idiopathic pulmonary fibrosis (IPF). Objectives: To identify novel variants in DSP associated with IPF and to characterize the relationship of these IPF sequence variants with DSP gene expression in human l...

Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that corre...

Supplemental Materials and Methods. (DOCX)

Agilent SureSelect Methyl Sequencing Summary. (DOCX)

Suggestive DMRs in HDM-treated CS vs FA mice. (DOCX)

DMR Validation and Transcript Levels. (DOCX)

DMR Subset Analysis Gene Lists. (DOCX)

Pathway analysis of Suggestive DMRs in HDM-treated CS and FA mice. (DOCX)

Longer sequencing reads, with at least 200 bases per template are now common. While traditional aligners have adopted new strategies to improve the mapping of longer reads, aligners specific to bisulfite-sequencing were optimized when much shorter reads were the norm. We sought to perform the first comparison using longer reads to determine which a...

Chronic exposure to hypoxia raises the risk of pregnancy disorders characterized by maternal vascular dysfunction and diminished fetal growth. In an effort to identify novel pathways for these hypoxiarelated effects, we assessed gene expression profiles of peripheral blood mononuclear cells (PBMCs) obtained from 43 female, high-altitude or sea-leve...

The biological significance of genomic features is often context-dependent. Annotating a particular dataset with existing, external data can provide insight into function. We present CruzDB, a fast and intuitive programmatic interface to the UCSC genome browser that facilitates integrative analyses of diverse local and remotely hosted datasets. We...

Loss of heterozygosity (LOH) is a common type of genomic alterations in ovarian cancer. Analyzing 74,415 copy neutral LOH events in 513 serous ovarian adenocarcinomas samples from the Cancer Genome Atlas, we report that the frequency of LOH events increases with age. Similar trend is observed for LOH involving chromosome 17, which is frequently imp...

Conserved non-coding sequences (CNS) are islands of non-coding sequence that, like protein coding exons, show less divergence in sequence between related species than functionless DNA. Several CNSs have been demonstrated experimentally to function as cis-regulatory regions. However, the specific functions of most CNSs remain unknown. Previous searc...

Erroneous repair of DNA double-strand breaks by homologous recombination (HR) leads to loss of heterozygosity (LOH). Analysing 22 392 and 74 415 LOH events in 363 glioblastoma and 513 ovarian cancer samples, respectively, and using three different metrics, we report that LOH selectively occurs in early replicating regions; this pattern differs from...

We performed a genome-wide association study of non-Hispanic, white individuals with fibrotic idiopathic interstitial pneumonias (IIPs; n = 1,616) and controls (n = 4,683), with follow-up replication analyses in 876 cases and 1,890 controls. We confirmed association with TERT at 5p15, MUC5B at 11p15 and the 3q26 region near TERC, and we identified...

comb-p is a command-line tool and a python library that manipulates BED files of possibly irregularly spaced P-values and (1) calculates auto-correlation, (2) combines adjacent P-values, (3) performs false discovery adjustment, (4) finds regions of enrichment (i.e. series of adjacent low P-values) and (5) assigns significance to those regions. In a...

The genome sequence of the paleohexaploid Brassica rapa shows that fractionation is biased among the three subgenomes and that the least fractionated subgenome has approximately twice as many orthologs as its close (and relatively unduplicated) relative Arabidopsis than had either of the other two subgenomes. One evolutionary scenario is that the t...

pybedtools is a flexible Python software library for manipulating and exploring genomic datasets in many common formats. It provides an intuitive Python interface that extends upon the popular BEDTools genome arithmetic tools. The library is well documented and efficient, and allows researchers to quickly develop simple, yet powerful scripts that e...

Although the era of big data has produced many bioinformatics tools and databases, using them effectively often requires specialized knowledge. Many groups lack bioinformatics expertise, and frequently find that software documentation is inadequate while local colleagues may be overburdened or unfamiliar with specific applications. Too often, such...

pybedtools is a flexible Python software library for manipulating and exploring genomic datasets in many common formats. It provides an intuitive Python interface that extends upon the popular BEDTools genome arithmetic tools. The library is well documented and efficient, and allows researchers to quickly develop simple, yet powerful scripts that e...

Motivation: MethylCoder is a software program that generates per-base methylation data given a set of bisulfite-treated reads. It provides the option to use either of two existing short-read aligners, each with different strengths. It accounts for soft-masked alignments and overlapping paired-end reads. MethylCoder outputs data in text and binary...

It is difficult to accurately interpret chromosomal correspondences such as true orthology and paralogy due to significant divergence of genomes from a common ancestor. Analyses are particularly problematic among lineages that have repeatedly experienced whole genome duplication (WGD) events. To compare multiple "subgenomes" derived from genome dup...

Whole genome duplications, or tetraploidies, are an important source of increased gene content. Following whole genome duplication, duplicate copies of many genes are lost from the genome. This loss of genes is biased both in the classes of genes deleted and the subgenome from which they are lost. Many or all classes are genes preferentially retain...

Unlabelled: Gobe is a web-based tool for viewing comparative genomic data. It supports viewing multiple genomic regions simultaneously. Its simple text format and flash-based rendering make it an interactive, exploratory research tool. Gobe can be used without installation through our web service, or downloaded and customized with stylesheets and...

The sorghum-maize dot-plot. Sorghum (x-axis) and maize (y-axis) with alpha-tetraploidy lines colored purple by lower Ks from SynMap in CoGe. Numerals are chromosome numbers. Lower Ks is more recent. Although hundreds of breakpoints are evident, each segment of maize is orthologous to one sorghum region, and each sorghum segment is orthologous to tw...

The sorghum gene list. Sorghum genes from 37 regions were from Sbi1.4 to which we added many genes on the basis of orthology to rice Niponbarre, TIGR 5; the added genes included many with corresponding RNAs since these are absent in Sbi1.4. SI1 uses the format Sbxgxxxxxx for Sbi1.4 genes and sorghum_chrmosomex_startx_stopx for genes we added based...

Fractionation runs used to determine bias for all 37 orthologous sorghum/maize regions. Here, bias is measured in units “genes lost completely.” The code we used, taken from the Dataset S1 datasheet (e.g. 11BBB1121B2121BBBB2222BB…), is given at the top of each diagram. Assuming that genes are lost in units of one gene, the null hypothesis is that t...

Generating the augmented sorghum gene list by comparison of sorghum to rice. We used a pipeline to generate the sorghum gene list of SI1. Given the input of the same genomes and annotation, this pipeline generates this list repeatedly. This sorghum gene list includes the JGI official annotated sorghum genes plus the output of this pipeline: sorghum...

The script used to run the genetic algorithm for Figure 5. The fitness of solutions in the evolutionary algorithm were scored using the Monte Carlo method as described in Methods (with the modification that rather than fixing the deletion length at 1 gene, deletion lengths were selected using the weighted averages generated by the evolutionary algo...

Maize-maize self-blastn dot-plot. Sequences present 40×X in the genome were masked. Axes are in genes from annotated psudomolecules from 10-09. Tangent angles = bias. Green lines are higher Ks and are from the alpha-tetraploidy. (1.60 MB PDF)

Whole-gene deletion in soybean (Glycine max). (A) A GEvo output of soybean homeologous regions from the alpha tetraploidy (panels 1 and 2), Medicago trunculata (panel 3), and the soybean homeologous regions from the beta tetraploidy event (panels 4 and 5). Circled is a gene in Medicago that has orthologs in all soybean homeologs except for soybean...

Previous work in Arabidopsis showed that after an ancient tetraploidy event, genes were preferentially removed from one of the two homologs, a process known as fractionation. The mechanism of fractionation is unknown. We sought to determine whether such preferential, or biased, fractionation exists in maize and, if so, whether a specific mechanism...

The 226 transposed genes used in our study. These are genes that have been confirmed as present at their site due to insertion in A. thaliana rather than loss in A. lyrata by using the two outgroups C. papaya and V. vitifera for comparison. Columns I and J provide a link to our GEvo platform to visualize the blast hits of the orthologous regions in...

All genes within the A. thaliana genome that are flanked by direct repeats, according to our algorithm described in Methods. The GEvo link is provided in Column K. (1.67 MB XLS)

Flanking direct repeats around transposed genes in Arabidopsis. Three examples of transposed genes surrounded by flanking repeats. For each figure, the middle panel represents the transposed gene (yellow), the top panel represents the sequence in A. lyrata that is the orthologous region to the transposed gene locus, and the bottom panel represents...

The best hits of all 126 transposed genes (excluding unknown genes). Column Q (Best hit alignment) provides a link to our GEvo platform to visualize the blast hits between the transposed gene and its best hit (if applicable). Column R (Flanking repeat alignment) provides a GEvo link to the flanking repeats surrounding the transposed gene (if any)....

The best hits of 102 non-transposed genes (if any). GEvo alignment (Best hit alignment) Column M, GEvo flanking repeat alignment (Flanking repeat alignment) Column N. (0.32 MB XLS)

Much of the eukaryotic genome is known to be mobile, largely due to the movement of transposons and other parasitic elements. Recent work in plants and Drosophila suggests that mobility is also a feature of many nontransposon genes and gene families. Indeed, analysis of the Arabidopsis genome suggested that as many as half of all genes had moved to...

Comparing the DNA sequence of maize genes and chromosomal regions to their maize homeologs and to other grass orthologs provides a quick check for many annotation errors and may identify useful regions of conservation and divergence. Fractionation and subfunctionalization, two processes that shape the evolution of genes and genomes, may be evaluate...

We find great value in the genomes from the nonmodel organisms papaya and grape. These genomes help us understand the chromosomal history of the super-order rosids. Essential to this process are new, online genomics tools that allow researchers to easily perform their own experiments, such as identifying and evaluating syntenic regions and estimati...

Previous to this work, typical genes were thought to move from one position to another infrequently. On the contrary, we now estimate that between one-fourth and three-fourths of the genes in Arabidopsis transposed in the Brassicales. We used the CoGe comparative genomics system to perform and visualize multiple orthologous chromosomal alignments....

In addition to the genomes of Arabidopsis (Arabidopsis thaliana) and poplar (Populus trichocarpa), two near-complete rosid genome sequences, grape (Vitis vinifera) and papaya (Carica papaya), have been recently released. The phylogenetic relationship among these four genomes and the placement of their three independent, fractionated tetraploidies s...

The recently established Center for Fire Research and Outreach at the University of California, Berkeley has developed a web-based toolkit, the Fire Information Engine Toolkit (FIET), for wildfire-related needs. The FIET is intended to meet the needs of diverse user groups (homeowners, decision-makers, including fire operations, and researchers) at...

A tetraploidy left Arabidopsis thaliana with 6358 pairs of homoeologs that, when aligned, generated 14,944 intragenomic conserved noncoding sequences (CNSs). Our previous work assembled these phylogenetic footprints into a database. We show that known transcription factor (TF) binding motifs, including the G-box, are overrepresented in these CNSs....

After the most recent tetraploidy in the Arabidopsis lineage, most gene pairs lost one, but not both, of their duplicates. We manually inspected the 3,179 retained gene pairs and their surrounding gene space still present in the genome using a custom-made viewer application. The display of these pairs allowed us to define intragenic conserved nonco...

Scientific datasets are often generated and used by "communities", or groups of users and creators. These communities, today often virtual, can include researchers, decision-makers, and the general public; participants in these communities may contribute different components during various iterations in the data generation process, and have differe...

Approximately 90% of Arabidopsis' unique gene content is found in syntenic blocks that were formed during the most recent whole-genome duplication. Within these blocks, 28.6% of the genes have a retained pair; the remaining genes have been lost from one of the homeologs. We create a minimized genome by condensing local duplications to one gene, rem...

The refuge strategy is central for delaying insect resistance to transgenic crops that produce Bacillus thuringiensis (Bt) toxins, but determining an effective spatial configuration of refuges has been problematic. We developed a spatially explicit, demographically based method for estimating the zone of influence of refuges, the area over which re...

Theoretical studies have presented conflicting conclusions about the value of introducing multiple parasitoid species to control insect pests, depending on the presence and form of niche separation in the model. We investigated the impacts of multiple species introduction on control using a modelling approach. We started with a discrete‐time model...

Cultural control methods have been central in the southwestern United States for reducing pink bollworm, Pectinophora gossypiella (Saunders), damage to cotton. Nevertheless, it is not clear at present how such methods could be integrated within the novel pest management framework allowed by introduction of cotton producing a toxin from Bacillus thu...

A major challenge for agriculture is management of insect resistance to toxins from Bacillus thuringiensis (Bt) produced by transgenic crops. Here we describe how a large-scale program is being developed in Arizona for management of resistance to Bt cotton in the pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae), and oth...

WGDs present a major challenge for accurately attributing synteny blocks to different evolutionary origins, especially when there are multiple sequential WGD events. In particular, some WGDs may be species-specific and others shared by multiple species. Identifying which genomic regions are the products of which duplication or speciation event is n...

Thesis (Ph. D. in Environmental Science, Policy, and Management)--University of California, Berkeley, Fall 2005. Includes bibliographical references.