Unequal group variances in microarray data analyses

Motivation: In searching for differentially expressed (DE) genesin microarray data, we often observe a fraction of the genesto have unequal variability between groups. This is not an issuein large samples, where a valid test exists that uses individualvariances separately. The problem arises in the small-samplesetting, where the approximately valid Welch test lacks sensitivity,while the more sensitive moderated t-test assumes equal variance. Methods: We introduce a moderated Welch test (MWT) that allowsunequal variance between groups. It is based on (i) weightingof pooled and unpooled standard errors and (ii) improved estimationof the gene-level variance that exploits the information fromacross the genes. Results: When a non-trivial proportion of genes has unequalvariability, false discovery rate (FDR) estimates based on thestandard t and moderated t-tests are often too optimistic, whilethe standard Welch test has low sensitivity. The MWT is shownto (i) perform better than the standard t, the standard Welchand the moderated t-tests when the variances are unequal betweengroups and (ii) perform similarly to the moderated t, and betterthan the standard t and Welch tests when the group variancesare equal. These results mean that MWT is more reliable thanother existing tests over wider range of data conditions. Availability: R package to perform MWT is available at http://www.meb.ki.se/~yudpaw Contact: yudi.pawitan{at}ki.se Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Martin Bishop     

Contribution of Crenarchaeota and Euryarchaeota to the prokaryotic plankton in the coastal northwestern Black Sea

Journal of Plankton Research, 29,     

ELECTROPHORETIC AND MORPHOMETRIC CHARACTERS IN POPULATION DIFERENTIATION OF THE PEARL OYSTER, PINCTADA RADIATA (LEACH), FROM AROUND BAHRAIN

Variation at the leucine aminopeptidase (Lap), glucose phosphateisomerase (Gpi) and tetrazolium oxidase (To) loci was investigatedin samples of three populations, Al-Mayana (MAY), Shigita (SH)and Mina Salman (MS), of Pinctada radiata from pearl oysterbeds around Bahrain. The To locus was monomor-phic. SignificantLap and Gpi heterozygote deficiencies were evident and it issuggested that these were generated by selection. The MS population,to the East of Bahrain, differed significantly in Gpi allelefrequencies from both Northern populations (MAY, SH) and Nei'sgenetic identity indicates a close relationship between theNorthern populations. Measurements of shell morphometrics were used both as ratiosof one dimension to another, and as regressions of one dimensionon another to examine relatedness between populations. Boththese mor-phometric approaches gave different results from eachother and also differed from the electrophoretic data. It isconcluded that estimates of relatedness in pearl oysters basedon electrophoretic data will be more reliable than those basedon shell shape. (Received 20 November 1990; accepted 12 April 1991)     

Gut evacuation rates and ingestion rates of Eudiaptomus graciloides measured by means of the gut fluorescence method

Journal of Plankton Research, 8, 973–983, 1986 FIg. 2. Time-dependent changes in the gut content (percentageof initial ng pigment) of E. gro.ciloides at different temperaturesunder simultaneous feeding. Fig. 4. The relationship between instantaneous evacuation rateand temperature of E. graciloides. The regresston equation forfeeding animals: y = 0.0044 e(0.141 ) (r² = 0.90). For comparisonthe results of non-feeding animals are indicated with open circles.     

Model-based deconvolution of genome-wide DNA binding

Motivation: Chromatin immunoprecipitation followed by hybridizationto a genomic tiling microarray (ChIP-chip) is a routinely usedprotocol for localizing the genomic targets of DNA-binding proteins.The resolution to which binding sites in this assay can be identifiedis commonly considered to be limited by two factors: (1) theresolution at which the genomic targets are tiled in the microarrayand (2) the large and variable lengths of the immunoprecipitatedDNA fragments. Results: We have developed a generative model of binding sitesin ChIP-chip data and an approach, MeDiChI, for efficientlyand robustly learning that model from diverse data sets. Wehave evaluated MeDiChI's performance using simulated data, aswell as on several diverse ChIP-chip data sets collected onwidely different tiling array platforms for two different organisms(Saccharomyces cerevisiae and Halobacterium salinarium NRC-1).We find that MeDiChI accurately predicts binding locations toa resolution greater than that of the probe spacing, even foroverlapping peaks, and can increase the effective resolutionof tiling array data by a factor of 5x or better. Moreover,the method's performance on simulated data provides insightsinto effectively optimizing the experimental design for increasedbinding site localization accuracy and efficacy. Availability: MeDiChI is available as an open-source R package,including all data, from http://baliga.systemsbiology.net/medichi. Contact: dreiss{at}systemsbiology.org Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Martin Bishop     

CORRIGENDUM

EAMES, F. E., 1968. New name for a Pakistan Eocene Turbonilla.Proc. malac. Soc. Lond. 38, 167. Line 4 : For J. Conch., Lond. p. 95, read Ann. Mag. Nat. Hist.(6) (6), 95.     

Floral Diversity and Pollen Transfer Mechanisms in Bird-pollinated Salvia Species

Annals of Botany 100:     

AIMIE: a web-based environment for detection and interpretation of significant sequence motifs in prokaryotic genomes

Motivation: Genomes contain biologically significant informationthat extends beyond that encoded in genes. Some of this informationrelates to various short dispersed repeats distributed throughoutthe genome. The goal of this work was to combine tools for detectionof statistically significant dispersed repeats in DNA sequenceswith tools to aid development of hypotheses regarding theirpossible physiological functions in an easy-to-use web-basedenvironment. Results: Ab Initio Motif Identification Environment (AIMIE)was designed to facilitate investigations of dispersed sequencemotifs in prokaryotic genomes. We used AIMIE to analyze theEscherichia coli and Haemophilus influenzae genomes in orderto demonstrate the utility of the new environment. AIMIE detectedrepeated extragenic palindrome (REP) elements, CRISPR repeats,uptake signal sequences, intergenic dyad sequences and severalother over-represented sequence motifs. Distributional patternsof these motifs were analyzed using the tools included in AIMIE. Availability: AIMIE and the related software can be accessedat our web site http://www.cmbl.uga.edu/software.html. Contact: mrazek{at}uga.edu Associate Editor: Alex Bateman     

Extrafloral Nectaries in Aspen (Populus tremuloides): Heritable Genetic Variation and Herbivore-induced Expression

Annals of Botany 100:     

PETALIFERA HABEI, A NEW SPECIES FROM JAPAN ADDENDUM

Since Petalifera habei was described in the Proceedings, 34,1, 12–18, April 1960, I have received from Dr. K. Babaa short account of the same species in Publ. Seto. mar. biol.Lab. 7, 3, 337–338. December, 1959, under the title "Thegenus Petalifera and a new species, P. ramosa, from Japan".I was unaware that Dr. Baba intended to describe it. As hispaper antedates mine, his name, Petalifera ramosa, must replaceP. Habei.     

Robust accurate identification of peptides (RAId): deciphering MS2 data using a structured library search with de novo based statistics

Motivation: The key to MS -based proteomics is peptide sequencing.The major challenge in peptide sequencing, whether library searchor de novo, is to better infer statistical significance andbetter attain noise reduction. Since the noise in a spectrumdepends on experimental conditions, the instrument used andmany other factors, it cannot be predicted even if the peptidesequence is known. The characteristics of the noise can onlybe uncovered once a spectrum is given. We wish to overcome suchissues. Results: We designed RAId to identify peptides from their associatedtandem mass spectrometry data. RAId performs a novel de novosequencing followed by a search in a peptide library that wecreated. Through de novo sequencing, we establish the spectrum-specificbackground score statistics for the library search. When thedatabase search fails to return significant hits, the top-rankingde novo sequences become potential candidates for new peptidesthat are not yet in the database. The use of spectrum-specificbackground statistics seems to enable RAId to perform well evenwhen the spectral quality is marginal. Other important featuresof RAId include its potential in de novo sequencing alone andthe ease of incorporating post-translational modifications. Availability: Programs implementing the methods described areavailable from the authors on request. Contact: yyu{at}ncbi.nlm.nih.gov Supplementary information: ftp://ftp.ncbi.nih.gov/pub/yyu/Proteomics/MSMS/RAId/MSMS_bioinfo_supp.pdf     

Observation of multiple folding pathways of beta-hairpin trpzip2 from independent continuous folding trajectories

Motivation: After 10-year investigations, the folding mechanismsof β-hairpins are still under debate. Experiments stronglysupport zip-out pathway, while most simulations prefer the hydrophobiccollapse model (including middle-out and zip-in pathways). Inthis article, we show that all pathways can occur during thefolding of β-hairpins but with different probabilities.The zip-out pathway is the most probable one. This is in agreementwith the experimental results. We came to our conclusions by38 100-ns room-temperature all-atom molecular dynamics simulationsof the β-hairpin trpzip2. Our results may help to clarifythe inconsistencies in the current pictures of β-hairpinfolding mechanisms. Contact: yxiao{at}mail.hust.edu.cn Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Anna Tramontano     

Analysis of Concentration-response Relationship for Enhanced Sugar Responses of the Chorda Tympani Nerve in the Diabetic db/db Mouse

Chorda tympani responses to sugars were greater in diabetic(db/db) than in non-diabetic control mice. A kinetic analysissuggested that the greater sugar responses in db/db mice wereunlikely due to the increased number of sugar receptors. Chem.Senses 21: 59–63, 1996.     

Tintinnids and other microzooplankton--seasonal distributions and relationships to resources and hydrography in a Maine estuary

Journal of Plankton Research, 9, 65–77, 1987. In Table II on page 70 the number of Tintinnopsis minuta foundat 0 m depth on 15 September 1981 should be 1200.     

MHC Class II DRB Variability and Parasite Load in the Striped Mouse (Rhabdomys pumilio) in the Southern Kalahari

doi:10.1093/molbev/msi112 Mol. Biol. Evol. 22     

Influence of the 3'-UTR-length of mKIAA cDNAs and their Sequence Features to the mRNA Expression Level in the Brain

We have previously described the sequence features of 1500 mouseKIAA (mKIAA) genes in comparison with those of human KIAA genes(Okazaki, N., Kikuno, R., Inamoto, S., Hara, Y., Nagase, T.,Ohara, O., and Koga, H. 2002, DNA Res., 9, 179–188; Okazaki,N., Kikuno, R., Ohara, R., Inamoto, S., Aizawa, H., Yuasa, S.,Nakajima, D., Nagase, T., Ohara, O., and Koga, H. 2003, DNARes., 10, 35–48; Okazaki, N., Kikuno, R., Ohara, R., Inamoto,S., Koseki, H., Hiraoka, S., Saga, Y., Nagase, T., Ohara, O.,and Koga, H. 2003, DNA Res., 10, 167–180; and Okazaki,N., F-Kikuno, R., Ohara, R., Inamoto, S., Koseki, H., Hiraoka,S., Saga, Y., Seino, S., Nishimura, M., Kaisho, T., Hoshino,K., Kitamura, H., Nagase, T., Ohara, O., and Koga, H. 2004,DNA Res., 11, 205–218). To validate the orthologous relationshipbetween mKIAA and KIAA genes in detail, we examined their chromosomalpositions and evolutionary rate of synonymous substitutionsand confirmed that >93% of the mKIAA/KIAA gene pairs areorthologous. During the sequence analysis of mKIAA genes, wefound that 3'-untranslated region (3'-UTR) lengths of mKIAAand KIAA genes are extremely long. In the meanwhile, we havealso examined the tissue-specific expression of 1700 mKIAA genesusing cDNA microarray and verified predominantly their expressionin adult brain (Koga, H., Yuasa, S., Nagase, T., Shimada, K.,Nagano, M., Imai, K., Ohara, R., Nakajima, D., Murakami, M.,Kawai, M., Miki, F., Magae, J., Inamoto, S., Okazaki, N., Ohara,O. 2004, DNA Res., 11, 293–304). To connect these twoevidences, we statistically analysed the relationship betweenthem by using the mKIAA genes. Consequently, a positive correlationwas observed between the 3'-UTR lengths and the relative expressionintensities in adult brain. Furthermore, we searched sequenceelements in the 3'-UTR possibly related with their expressionand found some candidates regarding the brain-specific expression.     

Effects of Calmodulin Antisense Oligonucleotides on Chemoresponse in Paramecium

The calcium/calmodulin-regulated Ca-ATPase of the plasma membraneis implicated in Paramecium chemosensory transduction. Calmodulinantisense oligonucleotides electroporated into Paramecium disruptchemosensory responses to sodium acetate but not to ammoniumchloride. Chem. Senses 21: 55–58, 1996.     

'ANOVA-simultaneous component analysis (ASCA): a new tool for analyzing designed metabolomics data'

Smilde et al. Bioinformatics (2005), 21(13); 3043–3048 The above paper by Smilde et al. inappropriately quotes results