Integrated environmental assessment and management, 2015
Life cycle assessment (LCA) has considerable merit for holistic evaluation of product planning, d... more Life cycle assessment (LCA) has considerable merit for holistic evaluation of product planning, development, production and disposal with the inherent benefit of providing a forecast of potential health and environmental impacts. However, a technical review of current LCIA methods revealed limitations within the biological effects assessment protocols, including: simplistic assessment approaches and models; an inability to integrate emerging types of toxicity data; a reliance on linear impact assessment models; a lack of methods to mitigate uncertainty; and no explicit consideration of effects in species of concern. The purpose of the present study is to demonstrate that a new concept in toxicological and regulatory assessment, the adverse outcome pathway (AOP), has many useful attributes of potential use to ameliorate many of these problems, to expand data utility and model robustness, and to enable more accurate and defensible biological effects assessments within LCIA. Background...
2012 IEEE 12th International Conference on Bioinformatics & Bioengineering (BIBE), 2012
ABSTRACT Structural analysis over well studied transcriptional regulatory networks indicates that... more ABSTRACT Structural analysis over well studied transcriptional regulatory networks indicates that these complex networks are made up of small set of reoccurring patterns called motifs. While information theoretic approaches have been immensely popular, these approaches rely on inferring the regulatory networks by aggregating pair-wise interactions. In this paper, we propose novel structure based information theoretic approaches to infer transcriptional regulatory networks from the microarray expression data. The core idea is to go beyond pair-wise interactions and consider more complex structures as found in motifs. While this increases the network inference complexity over pair-wise interaction based approaches, it achieves much higher accuracy and yet is scalable to genome-level inference. Detailed performance analyses based on benchmark precision and recall metrics on the known Escherichia coli's transcriptional regulatory network indicates that the accuracy of the proposed algorithms is consistently higher in comparison to popular algorithms such as context likelihood of relatedness (CLR), relevance networks (RN) and GEneNetwork Inference with Ensemble of trees (GENIE3). In the proposed approaches the size of structures was limited to three node cases (any node and its two parents). Analysis on a smaller network showed that the performance of the algorithm improved when more complex structures were considered for inference, although such higher level structures may be computationally challenging to infer networks at the genome scale.
We assessed the impacts of exposure to an environmentally representative concentration (0.83 mg/L... more We assessed the impacts of exposure to an environmentally representative concentration (0.83 mg/L) of the explosive cyclotrimethylenetrinitramine (RDX) on fathead minnows (Pimephales promelas) in one-year and multigenerational bioassays. In the one-year bioassay, impacts were assessed by statistical comparisons of females from breeding groups reared in control or RDX-exposure conditions. The RDX had no significant effect on gonadosomatic index or condition factor assayed at 1 d and at one, three, six, nine, and 12 months. The liver-somatic index was significantly increased versus controls only at the 12-month timepoint. RDX had no significant effect on live-prey capture rates, egg production, or fertilization. RDX caused minimal differential-transcript expression with no consistent discernable effect on gene-functional categories for either brain or liver tissues in the one-year exposure. In the multigenerational assay, the effects of acute (96 h) exposure to RDX were compared in fish reared to the F(2) generation in either control or RDX-exposure conditions. Enrichment of gene functions including neuroexcitatory glutamate metabolism, sensory signaling, and neurological development were observed comparing control-reared and RDX-reared fish. Our results indicated that exposure to RDX at a concentration representing the highest levels observed in the environment (0.83 mg/L) had limited impacts on genomic, individual, and population-level endpoints in fathead minnows in a one-year exposure. However, multigenerational exposures altered transcript expression related to neural development and function. Environ.
Rapid advances are being made in the creation and use of nanomaterials, but little is known about... more Rapid advances are being made in the creation and use of nanomaterials, but little is known about the impact these materials might have on key microbial functions if introduced into the environment. Previous studies have generated conflicting results with respect to the impact of fullerenes on microbial activity. In the present study, Salmonella typhimurium TA100 was selected as a model microbial system with which to investigate further the impact of C(60) aggregates on microbial growth, mutagenicity, and global transcript expression. Aggregates of C(60) predominantly less than 100 nm significantly impacted Salmonella growth at concentrations of ≥ 0.5 mg/L. In addition, C(60) aggregates also displayed mutagenic potential at concentrations ≥ 0.1 mg/L. Transcript expression analysis of S. typhimurium TA100 exposed to C(60) for 24 h indicated that 271 transcripts had significant differential expression relative to controls with twofold or more change. Of particular interest was the increased expression of transcripts coding for proteins involved in energy metabolism, amino acid biosynthesis, transcription, and DNA metabolism, and the decreased expression of transcripts coding for proteins involved in protein fate, transport, and binding and bacterial secretion systems. Collectively, these data indicate that C(60) interacts with the outer membrane of S. typhimurium TA100, resulting in delayed growth and mutagenicity, most likely by interfering with key transport functions and inducing a stress response, respectively.
Integrated environmental assessment and management, 2015
Life cycle assessment (LCA) has considerable merit for holistic evaluation of product planning, d... more Life cycle assessment (LCA) has considerable merit for holistic evaluation of product planning, development, production and disposal with the inherent benefit of providing a forecast of potential health and environmental impacts. However, a technical review of current LCIA methods revealed limitations within the biological effects assessment protocols, including: simplistic assessment approaches and models; an inability to integrate emerging types of toxicity data; a reliance on linear impact assessment models; a lack of methods to mitigate uncertainty; and no explicit consideration of effects in species of concern. The purpose of the present study is to demonstrate that a new concept in toxicological and regulatory assessment, the adverse outcome pathway (AOP), has many useful attributes of potential use to ameliorate many of these problems, to expand data utility and model robustness, and to enable more accurate and defensible biological effects assessments within LCIA. Background...
2012 IEEE 12th International Conference on Bioinformatics & Bioengineering (BIBE), 2012
ABSTRACT Structural analysis over well studied transcriptional regulatory networks indicates that... more ABSTRACT Structural analysis over well studied transcriptional regulatory networks indicates that these complex networks are made up of small set of reoccurring patterns called motifs. While information theoretic approaches have been immensely popular, these approaches rely on inferring the regulatory networks by aggregating pair-wise interactions. In this paper, we propose novel structure based information theoretic approaches to infer transcriptional regulatory networks from the microarray expression data. The core idea is to go beyond pair-wise interactions and consider more complex structures as found in motifs. While this increases the network inference complexity over pair-wise interaction based approaches, it achieves much higher accuracy and yet is scalable to genome-level inference. Detailed performance analyses based on benchmark precision and recall metrics on the known Escherichia coli's transcriptional regulatory network indicates that the accuracy of the proposed algorithms is consistently higher in comparison to popular algorithms such as context likelihood of relatedness (CLR), relevance networks (RN) and GEneNetwork Inference with Ensemble of trees (GENIE3). In the proposed approaches the size of structures was limited to three node cases (any node and its two parents). Analysis on a smaller network showed that the performance of the algorithm improved when more complex structures were considered for inference, although such higher level structures may be computationally challenging to infer networks at the genome scale.
We assessed the impacts of exposure to an environmentally representative concentration (0.83 mg/L... more We assessed the impacts of exposure to an environmentally representative concentration (0.83 mg/L) of the explosive cyclotrimethylenetrinitramine (RDX) on fathead minnows (Pimephales promelas) in one-year and multigenerational bioassays. In the one-year bioassay, impacts were assessed by statistical comparisons of females from breeding groups reared in control or RDX-exposure conditions. The RDX had no significant effect on gonadosomatic index or condition factor assayed at 1 d and at one, three, six, nine, and 12 months. The liver-somatic index was significantly increased versus controls only at the 12-month timepoint. RDX had no significant effect on live-prey capture rates, egg production, or fertilization. RDX caused minimal differential-transcript expression with no consistent discernable effect on gene-functional categories for either brain or liver tissues in the one-year exposure. In the multigenerational assay, the effects of acute (96 h) exposure to RDX were compared in fish reared to the F(2) generation in either control or RDX-exposure conditions. Enrichment of gene functions including neuroexcitatory glutamate metabolism, sensory signaling, and neurological development were observed comparing control-reared and RDX-reared fish. Our results indicated that exposure to RDX at a concentration representing the highest levels observed in the environment (0.83 mg/L) had limited impacts on genomic, individual, and population-level endpoints in fathead minnows in a one-year exposure. However, multigenerational exposures altered transcript expression related to neural development and function. Environ.
Rapid advances are being made in the creation and use of nanomaterials, but little is known about... more Rapid advances are being made in the creation and use of nanomaterials, but little is known about the impact these materials might have on key microbial functions if introduced into the environment. Previous studies have generated conflicting results with respect to the impact of fullerenes on microbial activity. In the present study, Salmonella typhimurium TA100 was selected as a model microbial system with which to investigate further the impact of C(60) aggregates on microbial growth, mutagenicity, and global transcript expression. Aggregates of C(60) predominantly less than 100 nm significantly impacted Salmonella growth at concentrations of ≥ 0.5 mg/L. In addition, C(60) aggregates also displayed mutagenic potential at concentrations ≥ 0.1 mg/L. Transcript expression analysis of S. typhimurium TA100 exposed to C(60) for 24 h indicated that 271 transcripts had significant differential expression relative to controls with twofold or more change. Of particular interest was the increased expression of transcripts coding for proteins involved in energy metabolism, amino acid biosynthesis, transcription, and DNA metabolism, and the decreased expression of transcripts coding for proteins involved in protein fate, transport, and binding and bacterial secretion systems. Collectively, these data indicate that C(60) interacts with the outer membrane of S. typhimurium TA100, resulting in delayed growth and mutagenicity, most likely by interfering with key transport functions and inducing a stress response, respectively.
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