PhenoMeter: A Metabolome Database Search Tool Using Statistical Similarity Matching of Metabolic Phenotypes for High-Confidence Detection of Functional Links

This article describes PhenoMeter, a new type of metabolomics database search that accepts metabolite response patterns as queries and searches the MetaPhen database of reference patterns for responses that are statistically significantly similar or inverse for the purposes of detecting functional links. To identify a similarity measure that would detect functional links as reliably as possible, we compared the performance of four statistics in correctly top-matching metabolic phenotypes of Arabidopsis thaliana metabolism mutants affected in different steps of the photorespiration metabolic pathway to reference phenotypes of mutants affected in the same enzymes by independent mutations. The best performing statistic, the PhenoMeter Score (PM Score), was a function of both Pearson correlation and Fisher’s Exact Test of directional overlap. This statistic outperformed Pearson correlation, biweight midcorrelation and Fisher’s Exact Test used alone. To demonstrate general applicability, we show that the PhenoMeter reliably retrieved the most closely functionally-linked response in the database when queried with responses to a wide variety of environmental and genetic perturbations. Attempts to match metabolic phenotypes between independent studies were met with varying success and possible reasons for this are discussed. Overall, our results suggest that integration of pattern-based search tools into metabolomics databases will aid functional annotation of newly recorded metabolic phenotypes analogously to the way sequence similarity search algorithms have aided the functional annotation of genes and proteins. PhenoMeter is freely available at MetabolomeExpress (https://www.metabolome-express.org/phenometer.php)

Effect of Percent Fines in Pelleted Diets on Growth Performance of Grow-Finish Pigs During Three Phases of Production

Swine feed is commonly pelleted to improve F/G, feed handling characteristics, and bulk density. However, the degree of improvement in F/G of pigs depends on pellet quality or the percent fines at the feeder. The objective of this study was to determine if the response to pellet quality was dependent on the BW range of grow-finish pigs. Therefore, a total of 350 pigs (initially 80 lb; line 600 × 241, DNA) were randomly placed in 35 pens with 10 pigs per pen (5 barrows and 5 gilts per pen). All pigs were fed a common diet until the onset of the first experiment. At this time, pens of pigs were weighed to determine average pig weight per pen and split into 7 blocks based on average pen weight. Treatments were randomly assigned to pens within block. There was a total of 5 treatments with 7 replications per treatment. For Exp. 1, 2, and 3, pigs were fed treatments for 20 days from 96 to 150 lb, 21 days from 179 to 234 lb, and 20 days from 260 to 317 lb, respectively. Between each experiment, a 10-day washout period was utilized to mitigate any residual effects from the previous experiment and pens were rerandomized to treatment before the start of each experiment. Treatments consisted of 10% fines (screened pellets), pellets with increasing fines inclusions (45, 65, and 85% fines), and mashed feed. Experiment 1 (96 to 150 lb) treatments contained 90.4, 67.6, 46.4, and 12.5% fines at the feeder. There was no evidence of differences in ADG or ADFI in pigs fed the mash diet compared to those fed any of the pelleted treatments. However, pigs fed pellets with 12.5% fines had improved (P \u3c 0.05) F/G compared to those fed mash diets. Pig ADFI and total feed cost increased (linear, P \u3e 0.006) in those fed pelleted diets with an increasing percentage of fines. Pigs fed pelleted diets with increasing percentage of fines (linear, P = 0.002) had poorer F/G. Experiment 2 (179 to 235 lb) treatments consisted of 86.0, 60.5, 43.6, and 15.5% fines at the feeder. There was no evidence of differences in ADG. Pigs fed 86.0% fines had a tendency for increased (P \u3c 0.1) ADFI and poorer F/G when compared to the mash diet. Therefore, total feed cost increased (P \u3c 0.05) for pigs fed pellets with 86.0% fines when compared to pigs fed the mash diet. However, pigs fed pellets with 15.5% fines had improved (P \u3c 0.05) F/G compared to those fed mash diets. For pigs fed pelleted diets, increasing percentage of fines increased (linear, P = 0.016) ADFI which resulted in poorer (linear, P \u3c 0.02) F/G, total feed cost, and income over feed cost (IOFC). Experiment 3 (260 to 317 lb) pelleted diets contained 83.6, 65.1, 41.8, and 9.6% fines at the feeder. There was no evidence of differences in ADG or ADFI for pigs fed pellets with 65.1, 41.8, or 9.6% fines compared to those fed the mash diet. Pigs fed 83.6% fines had increased (P \u3c 0.05) total feed cost per pig and a tendency for increased (P \u3c 0.1) ADFI when compared to pigs fed the mash diet. Pig F/G improved (P \u3c 0.05) when fed 9.6 and 41.8% fines compared to those fed mash diets. Pigs fed 65.1% fines had a tendency for improved (P \u3c 0.1) F/G when compared to pigs fed the mash diet. Income over feed cost improved (P \u3c 0.05) in pigs fed pellets with 9.6% fines when compared to those fed the mash diet. Pig F/G became poorer (linear, P = 0.0056) as percent fines increased in the pelleted diets. Pelleted diets with fines increasing from 9.6 to 83.6% tended to increase (linear, P = 0.0874) total feed cost. In conclusion, feeding pigs 12.5, 15.5, and 9.6% fines in Exp. 1, 2, and 3 improved F/G by 4.1, 4.5, and 6.7%, respectively, compared to pigs fed mashed diets. Increasing the percent fines from 12.5 to 90.4%, 15.5 to 86.0%, and 9.6 to 83.6% reduced F/G of pigs by 5.9, 8.6, and 6.4% for Exp. 1, 2, and 3, respectively

Effect of Percent Fines in Pelleted Diets on Growth Performance of Grow-Finish Pigs During Three Phases of Production

Swine feed is commonly pelleted to improve F/G, feed handling characteristics, and bulk density. However, the degree of improvement in F/G of pigs depends on pellet quality or the percent fines at the feeder. The objective of this study was to determine if the response to pellet quality was dependent on the BW range of grow-finish pigs. Therefore, a total of 350 pigs (initially 80 lb; line 600 × 241, DNA) were randomly placed in 35 pens with 10 pigs per pen (5 barrows and 5 gilts per pen). All pigs were fed a common diet until the onset of the first experiment. At this time, pens of pigs were weighed to determine average pig weight per pen and split into 7 blocks based on average pen weight. Treatments were randomly assigned to pens within block. There was a total of 5 treatments with 7 replications per treatment. For Exp. 1, 2, and 3, pigs were fed treatments for 20 days from 96 to 150 lb, 21 days from 179 to 234 lb, and 20 days from 260 to 317 lb, respectively. Between each experiment, a 10-day washout period was utilized to mitigate any residual effects from the previous experiment and pens were rerandomized to treatment before the start of each experiment. Treatments consisted of 10% fines (screened pellets), pellets with increasing fines inclusions (45, 65, and 85% fines), and mashed feed. Experiment 1 (96 to 150 lb) treatments contained 90.4, 67.6, 46.4, and 12.5% fines at the feeder. There was no evidence of differences in ADG or ADFI in pigs fed the mash diet compared to those fed any of the pelleted treatments. However, pigs fed pellets with 12.5% fines had improved (P \u3c 0.05) F/G compared to those fed mash diets. Pig ADFI and total feed cost increased (linear, P \u3e 0.006) in those fed pelleted diets with an increasing percentage of fines. Pigs fed pelleted diets with increasing percentage of fines (linear, P = 0.002) had poorer F/G. Experiment 2 (179 to 235 lb) treatments consisted of 86.0, 60.5, 43.6, and 15.5% fines at the feeder. There was no evidence of differences in ADG. Pigs fed 86.0% fines had a tendency for increased (P \u3c 0.1) ADFI and poorer F/G when compared to the mash diet. Therefore, total feed cost increased (P \u3c 0.05) for pigs fed pellets with 86.0% fines when compared to pigs fed the mash diet. However, pigs fed pellets with 15.5% fines had improved (P \u3c 0.05) F/G compared to those fed mash diets. For pigs fed pelleted diets, increasing percentage of fines increased (linear, P = 0.016) ADFI which resulted in poorer (linear, P \u3c 0.02) F/G, total feed cost, and income over feed cost (IOFC). Experiment 3 (260 to 317 lb) pelleted diets contained 83.6, 65.1, 41.8, and 9.6% fines at the feeder. There was no evidence of differences in ADG or ADFI for pigs fed pellets with 65.1, 41.8, or 9.6% fines compared to those fed the mash diet. Pigs fed 83.6% fines had increased (P \u3c 0.05) total feed cost per pig and a tendency for increased (P \u3c 0.1) ADFI when compared to pigs fed the mash diet. Pig F/G improved (P \u3c 0.05) when fed 9.6 and 41.8% fines compared to those fed mash diets. Pigs fed 65.1% fines had a tendency for improved (P \u3c 0.1) F/G when compared to pigs fed the mash diet. Income over feed cost improved (P \u3c 0.05) in pigs fed pellets with 9.6% fines when compared to those fed the mash diet. Pig F/G became poorer (linear, P = 0.0056) as percent fines increased in the pelleted diets. Pelleted diets with fines increasing from 9.6 to 83.6% tended to increase (linear, P = 0.0874) total feed cost. In conclusion, feeding pigs 12.5, 15.5, and 9.6% fines in Exp. 1, 2, and 3 improved F/G by 4.1, 4.5, and 6.7%, respectively, compared to pigs fed mashed diets. Increasing the percent fines from 12.5 to 90.4%, 15.5 to 86.0%, and 9.6 to 83.6% reduced F/G of pigs by 5.9, 8.6, and 6.4% for Exp. 1, 2, and 3, respectively

The MetabolomeExpress Project: enabling web-based processing, analysis and transparent dissemination of GC/MS metabolomics datasets

<p>Abstract</p> <p>Background</p> <p>Standardization of analytical approaches and reporting methods via community-wide collaboration can work synergistically with web-tool development to result in rapid community-driven expansion of online data repositories suitable for data mining and meta-analysis. In metabolomics, the inter-laboratory reproducibility of gas-chromatography/mass-spectrometry (GC/MS) makes it an obvious target for such development. While a number of web-tools offer access to datasets and/or tools for raw data processing and statistical analysis, none of these systems are currently set up to act as a public repository by easily accepting, processing and presenting publicly submitted GC/MS metabolomics datasets for public re-analysis.</p> <p>Description</p> <p>Here, we present MetabolomeExpress, a new File Transfer Protocol (FTP) server and web-tool for the online storage, processing, visualisation and statistical re-analysis of publicly submitted GC/MS metabolomics datasets. Users may search a quality-controlled database of metabolite response statistics from publicly submitted datasets by a number of parameters (eg. metabolite, species, organ/biofluid etc.). Users may also perform meta-analysis comparisons of multiple independent experiments or re-analyse public primary datasets via user-friendly tools for t-test, principal components analysis, hierarchical cluster analysis and correlation analysis. They may interact with chromatograms, mass spectra and peak detection results via an integrated raw data viewer. Researchers who register for a free account may upload (via FTP) their own data to the server for online processing via a novel raw data processing pipeline.</p> <p>Conclusions</p> <p>MetabolomeExpress <url>https://www.metabolome-express.org</url> provides a new opportunity for the general metabolomics community to transparently present online the raw and processed GC/MS data underlying their metabolomics publications. Transparent sharing of these data will allow researchers to assess data quality and draw their own insights from published metabolomics datasets.</p

Causes of ice age intensification across the Mid-Pleistocene Transition

During the Mid-Pleistocene Transition (MPT; 1,200–800 kya), Earth’s orbitally paced ice age cycles intensified, lengthened from ~40,000 (~40 ky) to ~100 ky, and became distinctly asymmetrical. Testing hypotheses that implicate changing atmospheric CO2 levels as a driver of the MPT has proven difficult with available observations. Here, we use orbitally resolved, boron isotope CO2 data to show that the glacial to interglacial CO2 difference increased from ~43 to ~75 μatm across the MPT, mainly because of lower glacial CO2 levels. Through carbon cycle modeling, we attribute this decline primarily to the initiation of substantive dust-borne iron fertilization of the Southern Ocean during peak glacial stages. We also observe a twofold steepening of the relationship between sea level and CO2-related climate forcing that is suggestive of a change in the dynamics that govern ice sheet stability, such as that expected from the removal of subglacial regolith or interhemispheric ice sheet phase-locking. We argue that neither ice sheet dynamics nor CO2 change in isolation can explain the MPT. Instead, we infer that the MPT was initiated by a change in ice sheet dynamics and that longer and deeper post-MPT ice ages were sustained by carbon cycle feedbacks related to dust fertilization of the Southern Ocean as a consequence of larger ice sheets.Research was supported by National Environmental Research Council (NERC) Studentship NE/I528626/1 (to T.B.C.); NERC Grant NE/P011381/1 (to T.B.C., M.P.H., G.L.F., E.J.R., and P.A.W.); NERC Fellowships NE/K00901X/1 (to M.P.H.), NE/I006346/1 (to G.L.F. and R.D.P), and NE/H006273/1 (to R.D.P.); Royal Society Wolfson Awards (to G.L.F. and P.A.W.); Australian Research Council Laureate Fellowship FL1201000050 (to E.J.R.); Swiss National Science Foundation Grant PP00P2-144811 (to S.L.J.); ETH Research Grant ETH-04 11-1 (to S.L.J.); European Research Council Consolidator Grant (ERC CoG) Grant 617462 (to H.P.); and NERC UK IODP Grant NE/F00141X/1 (to P.A.W.)

Genome analysis and comparative genomics of a Giardia intestinalis assemblage E isolate

<p>Abstract</p> <p>Background</p> <p><it>Giardia intestinalis </it>is a protozoan parasite that causes diarrhea in a wide range of mammalian species. To further understand the genetic diversity between the <it>Giardia intestinalis </it>species, we have performed genome sequencing and analysis of a wild-type <it>Giardia intestinalis </it>sample from the assemblage E group, isolated from a pig.</p> <p>Results</p> <p>We identified 5012 protein coding genes, the majority of which are conserved compared to the previously sequenced genomes of the WB and GS strains in terms of microsynteny and sequence identity. Despite this, there is an unexpectedly large number of chromosomal rearrangements and several smaller structural changes that are present in all chromosomes. Novel members of the VSP, NEK Kinase and HCMP gene families were identified, which may reveal possible mechanisms for host specificity and new avenues for antigenic variation. We used comparative genomics of the three diverse <it>Giardia intestinalis </it>isolates P15, GS and WB to define a core proteome for this species complex and to identify lineage-specific genes. Extensive analyses of polymorphisms in the core proteome of <it>Giardia </it>revealed differential rates of divergence among cellular processes.</p> <p>Conclusions</p> <p>Our results indicate that despite a well conserved core of genes there is significant genome variation between <it>Giardia </it>isolates, both in terms of gene content, gene polymorphisms, structural chromosomal variations and surface molecule repertoires. This study improves the annotation of the <it>Giardia </it>genomes and enables the identification of functionally important variation.</p

The Bicarbonate Transporter Is Essential for Bacillus anthracis Lethality

In the pathogenic bacterium Bacillus anthracis, virulence requires induced expression of the anthrax toxin and capsule genes. Elevated CO2/bicarbonate levels, an indicator of the host environment, provide a signal ex vivo to increase expression of virulence factors, but the mechanism underlying induction and its relevance in vivo are unknown. We identified a previously uncharacterized ABC transporter (BAS2714-12) similar to bicarbonate transporters in photosynthetic cyanobacteria, which is essential to the bicarbonate induction of virulence gene expression. Deletion of the genes for the transporter abolished induction of toxin gene expression and strongly decreased the rate of bicarbonate uptake ex vivo, demonstrating that the BAS2714-12 locus encodes a bicarbonate ABC transporter. The bicarbonate transporter deletion strain was avirulent in the A/J mouse model of infection. Carbonic anhydrase inhibitors, which prevent the interconversion of CO2 and bicarbonate, significantly affected toxin expression only in the absence of bicarbonate or the bicarbonate transporter, suggesting that carbonic anhydrase activity is not essential to virulence factor induction and that bicarbonate, and not CO2, is the signal essential for virulence induction. The identification of this novel bicarbonate transporter essential to virulence of B. anthracis may be of relevance to other pathogens, such as Streptococcus pyogenes, Escherichia coli, Borrelia burgdorferi, and Vibrio cholera that regulate virulence factor expression in response to CO2/bicarbonate, and suggests it may be a target for antibacterial intervention