Predicting the binding preference of transcription factors to individual DNA k-mers

Motivation: Recognition of specific DNA sequences is a central mechanism by which transcription factors (TFs) control gene expression. Many TF-binding preferences, however, are unknown or poorly characterized, in part due to the difficulty associated with determining their specificity experimentally, and an incomplete understanding of the mechanisms governing sequence specificity. New techniques that estimate the affinity of TFs to all possible k-mers provide a new opportunity to study DNA–protein interaction mechanisms, and may facilitate inference of binding preferences for members of a given TF family when such information is available for other family members. Results: We employed a new dataset consisting of the relative preferences of mouse homeodomains for all eight-base DNA sequences in order to ask how well we can predict the binding profiles of homeodomains when only their protein sequences are given. We evaluated a panel of standard statistical inference techniques, as well as variations of the protein features considered. Nearest neighbour among functionally important residues emerged among the most effective methods. Our results underscore the complexity of TF–DNA recognition, and suggest a rational approach for future analyses of TF families. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.Canadian Institutes of Health ResearchOntario Research FundNational Institutes of Health (U.S.)National Human Genome Research Institute (U.S.

Merging Accountancy and Computer Information Systems Programs at Arizona State University:A Snapshot of Current Progress and Continuing Challenges

This article provides a brief report on progress and continuing challenges facing the recently merged accountancy and computer information systems programs at Arizona State University. It provides a case study of programmatic evolution and curricular redesign in information systems. Distinctions between computer information systems programs and programs in other functional areas of business are becoming blurred. Students are increasingly choosing to enter dual degree programs which combine computer information systems educational preparation with preparation in more traditional functional areas of business. Additionally, increasing numbers of recruiters are hiring students from both traditional functional areas and computer information systems programs. This report describes a curricular strategy involving the merged programs which integrates interleaved program delivery, heterogeneous cohorts, and an intertwined prerequisite structure

Contribution of Distinct Homeodomain DNA Binding Specificities to Drosophila Embryonic Mesodermal Cell-Specific Gene Expression Programs

Homeodomain (HD) proteins are a large family of evolutionarily conserved transcription factors (TFs) having diverse developmental functions, often acting within the same cell types, yet many members of this family paradoxically recognize similar DNA sequences. Thus, with multiple family members having the potential to recognize the same DNA sequences in cis-regulatory elements, it is difficult to ascertain the role of an individual HD or a subclass of HDs in mediating a particular developmental function. To investigate this problem, we focused our studies on the Drosophila embryonic mesoderm where HD TFs are required to establish not only segmental identities (such as the Hox TFs), but also tissue and cell fate specification and differentiation (such as the NK-2 HDs, Six HDs and identity HDs (I-HDs)). Here we utilized the complete spectrum of DNA binding specificities determined by protein binding microarrays (PBMs) for a diverse collection of HDs to modify the nucleotide sequences of numerous mesodermal enhancers to be recognized by either no or a single subclass of HDs, and subsequently assayed the consequences of these changes on enhancer function in transgenic reporter assays. These studies show that individual mesodermal enhancers receive separate transcriptional input from both I–HD and Hox subclasses of HDs. In addition, we demonstrate that enhancers regulating upstream components of the mesodermal regulatory network are targeted by the Six class of HDs. Finally, we establish the necessity of NK-2 HD binding sequences to activate gene expression in multiple mesodermal tissues, supporting a potential role for the NK-2 HD TF Tinman (Tin) as a pioneer factor that cooperates with other factors to regulate cell-specific gene expression programs. Collectively, these results underscore the critical role played by HDs of multiple subclasses in inducing the unique genetic programs of individual mesodermal cells, and in coordinating the gene regulatory networks directing mesoderm development.National Institutes of Health (U.S.) (Grant R01 HG005287

Optically reconfigurable microstrip UWB bandpass filters

This paper presents an optically reconfigurable microstrip ultra-wideband filter. A single optical switch comprised of a silicon wafer is activated using near infra-red light to select between either a bandpass or bandstop response. With the switch in the ON state, the circuit behaves as a bandpass filter while in the OFF state, the circuit behaves as a bandstop filter in the same frequency band. The proposed filter was designed, fabricated and tested. Its performance was evaluated through simulation and measurements

Mapping Copy Number Variation by Population Scale Genome Sequencing

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.Organismic and Evolutionary Biolog

Expression-Guided In Silico Evaluation of Candidate Cis Regulatory Codes for Drosophila Muscle Founder Cells

While combinatorial models of transcriptional regulation can be inferred for metazoan systems from a priori biological knowledge, validation requires extensive and time-consuming experimental work. Thus, there is a need for computational methods that can evaluate hypothesized cis regulatory codes before the difficult task of experimental verification is undertaken. We have developed a novel computational framework (termed “CodeFinder”) that integrates transcription factor binding site and gene expression information to evaluate whether a hypothesized transcriptional regulatory model (TRM; i.e., a set of co-regulating transcription factors) is likely to target a given set of co-expressed genes. Our basic approach is to simultaneously predict cis regulatory modules (CRMs) associated with a given gene set and quantify the enrichment for combinatorial subsets of transcription factor binding site motifs comprising the hypothesized TRM within these predicted CRMs. As a model system, we have examined a TRM experimentally demonstrated to drive the expression of two genes in a sub-population of cells in the developing Drosophila mesoderm, the somatic muscle founder cells. This TRM was previously hypothesized to be a general mode of regulation for genes expressed in this cell population. In contrast, the present analyses suggest that a modified form of this cis regulatory code applies to only a subset of founder cell genes, those whose gene expression responds to specific genetic perturbations in a similar manner to the gene on which the original model was based. We have confirmed this hypothesis by experimentally discovering six (out of 12 tested) new CRMs driving expression in the embryonic mesoderm, four of which drive expression in founder cells

Children at danger: injury fatalities among children in San Diego County

External causes of death are important in the pediatric population worldwide. We performed an analysis of all injury-fatalities in children between ages zero and 17 years, between January 2000 and December 2006, in San Diego County, California, United States of America. Information was obtained from the County of San Diego Medical Examiner’s database. External causes were selected and grouped by intent and mechanism. Demographics, location of death and relation between the injury mechanism and time of death were described. There were 884 medico-legal examinations, of which 480 deaths were due to external causes. There majority were males (328, 68.3%) and whites (190, 39.6%). The most prevalent mechanism of injury leading to death was road traffic accidents (40.2%), followed by asphyxia (22.7%) and penetrating trauma (17.7%). Unintentional injuries occurred in 65.8% and intentional injuries, including homicide and suicide, occurred in 24.2 and 9.4%, respectively. Death occurred at the scene in 196 cases (40.9%). Most deaths occurred in highways (35.3%) and at home (28%). One hundred forty-six patients (30.4%) died in the first 24 h. Seven percent died 1 week after the initial injury. Among the cases that died at the scene, 48.3% were motor vehicle accidents, 20.9% were victims of firearms, 6.5% died from poisoning, 5% from hanging, and 4% from drowning. External causes remain an important cause of death in children in San Diego County. Specific strategies to decrease road-traffic accidents and homicides must be developed and implemented to reduce the burden of injury-related deaths in children