Bayesian variable selection and data integration for biological regulatory networks

A substantial focus of research in molecular biology are gene regulatory networks: the set of transcription factors and target genes which control the involvement of different biological processes in living cells. Previous statistical approaches for identifying gene regulatory networks have used gene expression data, ChIP binding data or promoter sequence data, but each of these resources provides only partial information. We present a Bayesian hierarchical model that integrates all three data types in a principled variable selection framework. The gene expression data are modeled as a function of the unknown gene regulatory network which has an informed prior distribution based upon both ChIP binding and promoter sequence data. We also present a variable weighting methodology for the principled balancing of multiple sources of prior information. We apply our procedure to the discovery of gene regulatory relationships in Saccharomyces cerevisiae (Yeast) for which we can use several external sources of information to validate our results. Our inferred relationships show greater biological relevance on the external validation measures than previous data integration methods. Our model also estimates synergistic and antagonistic interactions between transcription factors, many of which are validated by previous studies. We also evaluate the results from our procedure for the weighting for multiple sources of prior information. Finally, we discuss our methodology in the context of previous approaches to data integration and Bayesian variable selection.Comment: Published in at http://dx.doi.org/10.1214/07-AOAS130 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Annotation-based meta-analysis of microarray experiments

We are developing software applications to perform meta-analysis of microarray experiments based on standardized experiment annotations aiming to identify similar experiments and cluster experiments. The applications were tested on files obtained from the ArrayExpress public repository. Annotation terms were used to compute experiment dissimilarities to find experiments related to a query experiment. These applications may motivate efforts of bench biologists to better annotate experiments

Structural risk assessment and aircraft fleet maintenance

In the present analysis, deterministic flaw growth analysis is used to project the failure distributions from inspection data. Inspection data is reported for each critical point in the aircraft. The data will indicate either a crack of a specific size or no crack. The crack length may be either less than, equal to, or greater than critical size for that location. Non-critical length cracks are projected to failure using the crack growth characteristics for that location to find the life when it will be at critical length. Greater-than-critical length cracks are projected back to determine the life at failure, that is, when it was at critical length. The same process is used as in the case of a non-critical crack except that the projection goes the other direction. These points, along with the critical length cracks are used to determine the failure distribution. To be able to use data from different aircraft to build a common failure distribution, a consistent life variable must be used. Aircraft life varies with the severity of the usage; therefore the number of flight hours for a particular aircraft must be modified by its usage factor to obtain a normalized life which can be compared with that from other aircraft

Trapping Set Enumerators for Repeat Multiple Accumulate Code Ensembles

The serial concatenation of a repetition code with two or more accumulators has the advantage of a simple encoder structure. Furthermore, the resulting ensemble is asymptotically good and exhibits minimum distance growing linearly with block length. However, in practice these codes cannot be decoded by a maximum likelihood decoder, and iterative decoding schemes must be employed. For low-density parity-check codes, the notion of trapping sets has been introduced to estimate the performance of these codes under iterative message passing decoding. In this paper, we present a closed form finite length ensemble trapping set enumerator for repeat multiple accumulate codes by creating a trellis representation of trapping sets. We also obtain the asymptotic expressions when the block length tends to infinity and evaluate them numerically.Comment: 5 pages, to appear in proc. IEEE ISIT, June 200

Site Characteristics Associated with Conventional and Unconventional Petroleum Development in West Virginia

Little research has been done on the characteristics of surface disturbance between conventional (C) and unconventional (UC) wells in West Virginia. To understand the impacts of petroleum development in West Virginia, a total of 296 conventional wells and 206 unconventional wells were digitized for the purposes of this study. Using a combination of spatial and resource-related data, the total land area impacted, forest fragmentation characteristics, and forest resource impacts were investigated between conventional and unconventional wells. A metric was developed to understand natural gas production per land area disturbed for both conventional and unconventional wells. The absolute magnitude of the footprint associated with the disturbed area of WV forestland in conjunction with four years (2009 to 2012) of gas-production activity was rather modest. An estimated 2,358 hectares were disturbed, of which 1,341 hectares were forested. About 73.3% of the estimated forest area removed was the result of unconventional production and 26.7% was the result of conventional production. The results indicate that the volume of gas production per unit of area disturbed was much greater for unconventional wells than conventional wells. The potential for greater production per unconventional well and the possibility of multiple unconventional wells per pad can be more beneficial to overall surface disturbance, than the conventional development needed to equal the same amount of unconventional production. Thus, public policies and regulations limiting the expansion of unconventional wells may have negative consequences associated with the magnitude of surface disturbance. Interestingly, in contrast to C wells and studies of UC wells in other regions, the findings for WV suggest that UC wells were most frequently on already-perforated forests, not on core forests. Thus, the impact on forest fragmentation in WV may be less than generally anticipated in other regions by some scientists

Light converts endosymbiotic fungus to pathogen, influencing seedling survival and host tree recruitment

Endophytic fungi that asymptomatically colonize plants^1^ are diverse and abundant in tropical ecosystems^2^. These organisms can be weakly pathogenic^3^ and/or mutualistic, frequently enabling plants to adapt to extreme environments, alter competitive abilities of host individuals and improve host fitness under abiotic or biotic stresses^4,5,6^. _Diplodia mutila_ is a symbiotic endophyte/plant pathogenic fungus infecting the palm _Iriartea deltoidea_^7^, which dominates many wet lowland Neotropical forests. The fungus is an asymptomatic endophyte in mature plants, and disease and mortality are expressed in some seedlings, while others remain disease free. Here we show that seedlings bearing the endophyte show enhanced resistance to insect herbivory. However, high light availability triggers pathogenicity of the fungus, while low light favors endosymbiotic development, constraining recruitment of endophyte-infested seedlings to the shaded understory by limiting survival of seedlings in direct light. These results provide evidence that patterns of plant abundance and the mechanisms maintaining tropical forest biodiversity are the result of a more complex interplay between abiotic and biotic environments than previously thought