Details of a Researcher - Tomita, Masaru

Papers - Tomita, Masaru

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Validating the significance of genomic properties of Chi sites from the distribution of all octamers in Escherichia coli

Arakawa K., Uno R., Nakayama Y., Tomita M.

Gene 392 ( 1-2 ) 239 - 246 2007.05

ISSN 03781119

Chi sites (5′-GCTGGTGG-3′) are homologous recombinational hotspot octamer sequences, which attenuate the exonuclease activity of RecBCD in Escherichia coli. They are overrepresented in the genome (1008 occurrences), preferentially located within coding regions (98%), oriented in the direction of replication (75%), and occur most commonly on the mRNA-synonymous sense strand of the double helix (79%). Previous statistical studies of the genome sequence suggested that these genomic properties of Chi sites appear to be related to their role in recombinational repair and therefore to replication and transcription. In this study, we employ three mathematical models to predict the properties of Chi sites from single nucleotide and multi-nucleotide compositions, and validate them statistically using the distribution of all octamer sequences in the entire genome, or exclusively within ORFs. The model based on the overall distribution of all octamers provided better predictions than the single nucleotide composition model, and the ORF and sense strand preference of Chi sites were shown to be within the standard deviation of all octamers. In contrast, the orientation bias of the Chi sites in the direction of replication was significant, although the bias was not as pronounced as with the single nucleotide composition model, suggesting a selective pressure related to the role of RecBCD in replication. © 2007 Elsevier B.V. All rights reserved.

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Roles of hemoglobin allostery in hypoxia-induced metabolic alterations in erythrocytes: Simulation and its verification by metabolome analysis

Kinoshita A., Tsukada K., Soga T., Hishiki T., Ueno Y., Nakayama Y., Tomita M., Suematsu M.

Journal of Biological Chemistry 282 ( 14 ) 10731 - 10741 2007.04

ISSN 00219258

When erythrocytes are exposed to hypoxia, hemoglobin (Hb) stabilizes in theT-state by capturing 2,3-bisphosphoglycerate. This process could reduce the intracellular pool of glycolytic substrates, jeopardizing cellular energetics. Recent observations suggest that hypoxia-induced activation of glycolytic enzymes is correlated with their release from Band III (BIII) on the cell membrane. Based on these data, we developed a mathematical model of erythrocyte metabolism and compared hypoxia-induced differences in predicted activities of the enzymes, their products, and cellular energetics between models with and without the interaction of Hb with BIII. The models predicted that the allostery-dependent Hb interaction with BIII accelerates consumption of upstream glycolytic substrates such as glucose 6-phosphate and increases downstream products such as phosphoenolpyruvate. This prediction was consistent with metabolomic data from capillary electrophoresis mass spectrometry. The hypoxia-induced alterations in the metabolites resulted from acceleration of glycolysis, as judged by increased conversion of [13C]glucose to [13C]lactate. The allostery-dependent interaction of Hb with BIII appeared to contribute not only to maintenance of energy charge but also to further synthesis of 2,3-bisphosphoglycerate, which could help sustain stabilization of T-state Hb during hypoxia. Furthermore, such an activation of glycolysis was not observed when Hb was stabilized in R-state by treating the cells with CO. These results suggest that Hb allostery in erythrocytes serves as an O2-sensing trigger that drives glycolytic acceleration to stabilize intracellular energetics and promote the ability to release O 2 from the cells. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

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Simulation study of methemoglobin reduction in erythrocytes: Differential contributions of two pathways to tolerance to oxidative stress

Kinoshita A., Nakayama Y., Kitayama T., Tomita M.

FEBS Journal 274 ( 6 ) 1449 - 1458 2007.03

ISSN 1742464X

Methemoglobin (metHb), an oxidized form of hemoglobin, is unable to bind and carry oxygen. Erythrocytes are continuously subjected to oxidative stress and nitrite exposure, which results in the spontaneous formation of metHb. To avoid the accumulation of metHb, reductive pathways mediated by cytochrome b5 or flavin, coupled with NADH-dependent or NADPH-dependent metHb reductases, respectively, keep the level of metHb in erythrocytes at less than 1% of the total hemoglobin under normal conditions. In this work, a mathematical model has been developed to quantitatively assess the relative contributions of the two major metHb-reducing pathways, taking into consideration the supply of NADH and NADPH from central energy metabolism. The results of the simulation experiments suggest that these pathways have different roles in the reduction of metHb; one has a high response rate to hemoglobin oxidation with a limited reducing flux, and the other has a low response rate with a high capacity flux. On the basis of the results of our model, under normal oxidative conditions, the NADPH-dependent system, the physiological role of which to date has been unclear, is predicted to be responsible for most of the reduction of metHb. In contrast, the cytochrome b5-NADH pathway becomes dominant under conditions of excess metHb accumulation, only after the capacity of the flavin-NADPH pathway has reached its limit. We discuss the potential implications of a system designed with two metHb-reducing pathways in human erythrocytes. © 2007 The Authors.

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A mathematical model for the Kai-protein-based chemical oscillator and clock gene expression rhythms in cyanobacteria

Miyoshi, Fumihiko ; Nakayama, Yoichi ; Kaizu, Kazunari ; Iwasaki, Hideo ; Tomita, Masaru

JOURNAL OF BIOLOGICAL RHYTHMS 22 ( 1 ) 69-80 - 80 2007.02

Research paper (scientific journal), Joint Work, ISSN 0748-7304

In the cyanobacterium, Synechococcus elongatus, most promoters are regulated by a circadian clock under continuous light (LL) conditions. Nevertheless, the basic circadian oscillation is primarily generated by alternating KaiC phosphorylation/dephosphorylation reactions at the posttranslational level. Indeed, the KaiC phosphorylation cycle was recently reconstituted in vitro by incubating KaiA, KaiB, and KaiC proteins with ATP. However, the molecular dynamics of this chemical oscillation and the mechanism that drives the circadian transcription/translation rhythms remain unknown. In this report, the KaiC phosphorylation cycle and the gene regulatory network in the cyanobacterial circadian system have been modeled. The model reproduces the robust KaiC phosphorylation cycle in the absence of de novo gene expression as is observed in vitro, as well as its coupling to transcriptional/translational feedback in LL conditions in vivo. Moreover, the model is consistent with most previous experiments, including various combinations of genetic knockout or overexpression of kai genes. It also predicts that multiple KaiC phosphorylation states and dynamic Kai protein interactions may be required for the cyanobacterial circadian system. © 2007 Sage Publications.

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Noise-reduction filtering for accurate detection of replication termini in bacterial genomes

Arakawa, Kazuharu ; Saito, Rintaro ; Tomita, Masaru

FEBS LETTERS 581 ( 2 ) 253-258 - 258 2007.01

Research paper (scientific journal), Joint Work, ISSN 0014-5793

Bacterial chromosomes are highly polarized in their nucleotide composition through mutational selection related to replication. Using compositional skews such as the GC skew, replication origin and terminus can be predicted in silico by observing the shift points. However, the genome sequence is affected by myriad functional requirements and selection on numerous subgenomic features, and elimination of this "noise" should lead to better predictions. Here, we present a noise-reduction approach that uses low-pass filtering through Fast Fourier transform coupled with cumulative skew graphs. It increases the prediction accuracy of the replication termini compared with previously documented methods based on genomic base composition. © 2006 Federation of European Biochemical Societies.

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eXpanda: an Integrated Platform for Network Analysis and Visualization

Negishi, Y., Nakamura, H., Yachie, N., Saito, R. and Tomita, M.

In silico Biology 7 ( 2 ) 141 - 144 2007

ISSN 13866338

Analysis and visualization of biological networks, such as protein-protein and protein-DNA interactions, are crucially important toward obtaining a thorough understanding of living systems. Here, we present an integrative software platform, eXpanda, which enables an analysis of a very broad range of biological networks, with a special focus on the extraction of characteristic topologies which potentially function as units in the networks. eXpanda is provided as a Perl library which gives full-automatic connections to various biological databases via a Perl programmable interface and can perform topological analysis based on graph theory. The results of these analyses are visualizable by vector graphics. eXpanda is under GNU General Public License. Software package, detailed documentations, source codes, and some sample scripts are downloadable at http://medcd.iab.keio.ac.jp/expanda/. © 2007 IOS Press. All rights reserved.

Restauro-G: A Rapid Genome Re-Annotation System for Comparative Genomics

Tamaki, S., Arakawa, K., Kono, N. and Tomita, M.

Genomics Proteomics Bioinformatics 5; 53-58(2007) 5 ( 1 ) 53-58 - 58 2007

Research paper (scientific journal), Joint Work, ISSN 16720229

Annotations of complete genome sequences submitted directly from sequencing projects are diverse in terms of annotation strategies and update frequencies. These inconsistencies make comparative studies difficult. To allow rapid data preparation of a large number of complete genomes, automation and speed are important for genome re-annotation. Here we introduce an open-source rapid genome re-annotation software system, Restauro-G, specialized for bacterial genomes. Restauro-G re-annotates a genome by similarity searches utilizing the BLAST-Like Alignment Tool, referring to protein databases such as UniProt KB, NCBI nr, NCBI COGs, Pfam, and PSORTb. Re-annotation by Restauro-G achieved over 98% accuracy for most bacterial chromosomes in comparison with the original manually curated annotation of EMBL releases. Restauro-G was developed in the generic bioinformatics workbench G-language Genome Analysis Environment and is distributed at http://restauro-g.iab.keio.ac.jp/under the GNU General Public License. © 2007 Beijing Genomics Institute.

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Computational analysis of microRNA-mediated antiviral defense in humans

Watanabe, Y., Kishi, A., Yachie, N., Kanai, A. and Tomita, M.

FEBS Letters 581 ( 24 ) 4603-4610 - 4610 2007

Research paper (scientific journal), Joint Work, ISSN 00145793

Recent studies have proposed the interesting perspective that viral gene expression is downregulated by host microRNAs (miRNAs), small non-coding RNAs well known as post-transcriptional gene regulators. We computationally predicted human miRNA target sites within 228 human-infecting and 348 invertebrate-infecting virus genomes, and we observed that human-infecting viruses were more likely than invertebrate-infecting ones to be targeted by human miRNAs. We listed 62 possible human miRNA-targeted viruses from 6 families, most of which consisted of single-stranded RNA viruses. These results suggest that miRNAs extensively mediate antiviral defenses in humans. © 2007 Federation of European Biochemical Societies.

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Polymer Entrapment in Polymerized Silicate for Preparing Highly Stable Capillary Coatings for CE and CE-MS

Monton, M., Tomita, M., Soga, T. and Ishihama, Y.

Analytical Chemistry 79 ( 20 ) 7838-7844 - 7844 2007

Research paper (scientific journal), Joint Work, ISSN 00032700

An easy-to-implement capillary coating strategy based on polymer entrapment in the network of polymerized silicate is described. In this manner, cationic polymers are tightiy fixed onto the inner wall of the capillary for electroosmotic flow control without necessitating complex surface modification chemistries. The resulting coated capillary exhibited good stability over a wide range of pH, good reproducibility, strong endurance in more than 300 electrophoretic runs, and tolerance of commonly employed organic solvent additives in CE. Applications in CE-MS analysis of biologically important anions as well as sample enrichment are shown. Additionally, it was used as a durable base for attachment of multiple layers of charged polymers on the wall, via electrostatic interaction with the preceding layer. Thus, two novel types of highly stable coated capillaries, one with anodic EOF and the other cathodic, were developed. © 2007 American Chemical Society.

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Phosphopeptide Enrichment by Aliphatic Hydroxy Acid-modified Metal Oxide Chromatography for Nano-LC-MS/MS in Proteomics Applications

Sugiyama, N., Masuda, T., Shinoda, K., Nakamura, A., Tomita, M. and Ishihama, Y.

Mol Cell Proteomics 6 ( 6 ) 1103-1109 - 1109 2007

Research paper (scientific journal), Joint Work, ISSN 15359476

We developed novel methods for phosphopeptide enrichment using aliphatic hydroxy acid-modified metal oxide chromatography (MOC). Titania and zirconia were successfully applied to enrich phosphopeptides with the aid of aliphatic hydroxy acids, such as lactic acid and β-hydroxypropanoic acid, to reduce the interaction between acidic non-phosphopeptides and the metal oxides. These methods removed the vast majority of non-phosphopeptides from phosphoprotein standard digests, and large numbers of phosphopeptides could be readily identified. The methods were coupled with nano-LC-MS/MS systems without difficulty. Recovery of phosphopeptides in MOC varied greatly from peptide to peptide, ranging from a few percent to 100%, and the average was almost 50%. Repeatability and linearity were satisfactory. In an examination of the cytoplasmic fraction of HeLa cells, more than 1000 phosphopeptides were identified using lactic acid-modified titania MOC and β-hydroxypropanoic acid-modified zirconia MOC, respectively. The overlap between phosphopeptides enriched by these two methods was 40%, and the combined results provided 1646 unique phosphopeptides. To our knowledge, this is the first successful application of a single MOC-based approach to phosphopeptide enrichment from complex biological samples such as cell lysates. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

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Statistical Analysis of Gene Expression in Innate Immune Responses: Dynamic Interactions between MicroRNA and Signaling Molecules

Piras, V., Selvarajoo, K., Fujikawa, N., Choi, S., Tomita, M., Giuliani, A. and Tsuchiya, M.

Genomics and Informatics 5 107-112 2007

Research paper (scientific journal), Joint Work

Multiple high throughput analyses monitor the response of E. coli to perturbations

Ishii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba, M., Hirai, K., Hoque, A., Yee, Ho, Pei., Kakazu, Y., Sugawara, K., Igarashi, S., Harada, S., Masuda, T., Sugiyama, N., Togashi, T., Hasegawa, M., Takai, T., Yugi, K., Arakawa, K., Iwata, N., Toya, Y., Nakayama, Y., Nishioka, T., Shimizu, K., Mori, H. and Tomita, M.

Science 316 ( 5824 ) 593-597 - 597 2007

Research paper (scientific journal), Joint Work, ISSN 00368075

Analysis of cellular components at multiple levels of biological information can provide valuable functional insights. We performed multiple high-throughput measurements to study the response of Escherichia coli cells to genetic and environmental perturbations. Analysis of metabolic enzyme gene disruptants revealed unexpectedly small changes in messenger RNA and proteins for most disruptants. Overall, metabolite levels were also stable, reflecting the rerouting of fluxes in the metabolic network. In contrast, E. coli actively regulated enzyme levels to maintain a stable metabolic state in response to changes in growth rate. E. coli thus seems to use complementary strategies that result in a metabolic network robust against perturbations.

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Network scaling invariants help to elucidate basic topological principles of proteins

Krishnan, A., Giuliani, A., Zbilut, J.P. and Tomita, M.

Journal of Proteome Research 6 ( 10 ) 3924-3934 - 3934 2007

Research paper (scientific journal), Joint Work, ISSN 15353893

The structural architecture of proteins continues to be an area of active research. Despite the difference in models dealing with the way proteins fold into their tertiary structures, it is recognized that small regions of proteins tend to fold independently and are then stabilized by interactions between these distinct subunits. However, there are a number of different definitions of what comprises an independent subunit. In the belief that an unequivocal definition of a domain must be based on the most fundamental property of protein 3D structure, namely, the adjacency matrix of inter-residues contact, we adopt a network representation of the protein. In this work, we used a well-established, global method for identifying modules in networks, without any specific reference to the kind of network being analyzed. The algorithm converges toward the maximization of the modularity of the given protein network and, in doing so, allows the representation of the residues of the protein in terms of their intramodule degree, z, and participation coefficient, P. We demonstrate that the labeling of residues in terms of these invariants allows for information-rich representations of the studied proteins as well as to sketch a new way to link sequence, structure, and the dynamical properties of proteins. We discovered a strong invariant character of protein molecules in terms of P/z characterization, pointing to a common topological design of all protein structures. This invariant representation, applied to different protein systems, enabled us to identify the possible functional role of high P/z residues during the folding process. Additionally, we observe a hierarchical behavior of protein structural organization that provides a sequence-secondary-tertiary structure link. The discovery of similar and repeatable scaling laws at different level of definitions going from hydrophobicity patterning along the sequence up to the size of an autonomous folding unit (AFU) and general contact distribution of the entire molecule suggest a hierarchical-like behavior of protein architecture. This implies the possibility to select different privileged scales of observation for deriving useful information on protein systems. © 2007 American Chemical Society.

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Inferring rules of Escherichia coli translational efficiency using an artificial neural network

Mori, K., Saito, R., Kikuchi, S. and Tomita, M.

BioSystems 90 ( 2 ) 414-420 - 420 2007

Research paper (scientific journal), Joint Work, ISSN 03032647

Although the machinery for translation initiation in Escherichia coli is very complicated, the translational efficiency has been reported to be predictable from upstream oligonucleotide sequences. Conventional models have difficulties in their generalization ability and prediction nonlinearity and in their ability to deal with a variety of input attributions. To address these issues, we employed structural learning by artificial neural networks to infer general rules for translational efficiency. The correlation between translational activities measured by biological experiments and those predicted by our method in the test data was significant (r = 0.78), and our method uncovered underlying rules of translational activities and sequence patterns from the obtained skeleton structure. The significant rules for predicting translational efficiency were (1) G- and A-rich oligonucleotide sequences, resembling the Shine-Dalgarno sequence, at positions -10 to -7; (2) first base A in the initiation codon; (3) transport/binding or amino acid metabolism gene function; (4) high binding energy between mRNA and 16S rRNA at positions -15 to -5. An additional inferred novel rule was that C at position -1 increases translational efficiency. When our model was applied to the entire genomic sequence of E. coli, translational activities of genes for metabolism and translational were significantly high. © 2006 Elsevier Ireland Ltd. All rights reserved.

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Computational Methods for MicroRNA Target Prediction

Watanabe, Y., Tomita, M. and Kanai, A.

Methods in Enzymology 427 65-86 - 86 2007

Research paper (scientific journal), Joint Work, ISSN 00766879

The discovery of microRNAs (miRNAs) has introduced a new paradigm into gene regulatory systems. Large numbers of miRNAs have been identified in a wide range of species, and most of them are known to downregulate translation of messenger RNAs (mRNAs) via imperfect binding of the miRNA to a specific site or sites in the 3′ untranslated region (UTR) of the mRNA. Identification of genes targeted by miRNAs is widely believed to be an important step toward understanding the role of miRNAs in gene regulatory networks. As part of the effort to understand interactions between miRNAs and their targets, computational algorithms have been developed based on observed rules for features such as the degree of hybridization between the two RNA molecules. These in silico approaches provide important tools for miRNA target detection, and together with experimental validation, help to reveal regulated targets of miRNAs. Here, we summarize the knowledge that has been accumulated about the principles of target recognition by miRNAs and the currently available computational methodologies for prediction of miRNA target genes. © 2007 Elsevier Inc. All rights reserved.

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Selection effects on the positioning of genes and gene structures from the interplay of replication and transcription in bacterial genomes

Arakawa, K. and Tomita, M.

Evolutionary Bioinformatics 3 279-286 - 286 2007

Research paper (scientific journal), Joint Work

Bacterial chromosomes are partly shaped by the functional requirements for effi cient replication, which lead to strand bias as commonly characterized by the excess of guanines over cytosines in the leading strand. Gene structures are also highly organized within bacterial genomes as a result of such functional constraints, displaying characteristic positioning and structuring along the genome. Here we analyze the gene structures in completely sequenced bacterial chromosomes to observe the positional constraints on gene orientation, length, and codon usage with regard to the positions of replication origin and terminus. Selection on these gene features is different in regions surrounding the terminus of replication from the rest of the genome, but the selection could be either positive or negative depending on the species, and these positional effects are partly attributed to the A-T enrichment near the terminus. Characteristic gene structuring relative to the position of replication origin and terminus is commonly observed among most bacterial species with circular chromosomes, and therefore we argue that the highly organized gene positioning as well as the strand bias should be considered for genomics studies of bacteria.

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In silico screening of archaeal tRNA-encoding genes having multiple introns with bulge-helix-bulge splicing motifs

Sugahara, J., Yachie, N., Arakawa, K. and Tomita, M.

RNA 13 ( 5 ) 671-681 - 681 2007

Research paper (scientific journal), Joint Work, ISSN 13558382

In archaeal species, several transfer RNA genes have been reported to contain endogenous introns. Although most of the introns are located at anticodon loop regions between nucleotide positions 37 and 38, a number of introns at noncanonical sites and six cases of tRNA genes containing two introns have also been documented. However, these tRNA genes are often missed by tRNAscan-SE, the software most widely used for the annotation of tRNA genes. We previously developed SPLITS, a computational tool to identify tRNA genes containing one intron at a noncanonical position on the basis of its discriminative splicing motif, but the software was limited in the detection of tRNA genes with multiple introns at noncanonical sites. In this study, we initially updated the system as SPLITSX in order to correctly predict known tRNA genes as well as novel ones with multiple introns. By a comprehensive search for tRNA genes in 29 archaeal genomes using SPLITSX, we listed 43 novel candidates that contain introns at noncanonical sites. As a result, 15 contained two introns and three contained three introns within the respective putative tRNA genes. Moreover, the candidates completely complemented all the codons of two archaeal species of uncultured methanogenic archaeon, RC-I and Thermofilum pendens Hrk 5, with novel candidates that were not detectable by tRNAscan-SE alone. Published by Cold Spring Harbor Laboratory Press. Copyright © 2007 RNA Society.

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Inhibitory effect of phosphoenolpyruvate on glycolytic enzymes in Escherichia coli

Ogawa, T., Mori, H., Tomita, M. and Yoshino, M.

Research in Microbiology 158 ( 2 ) 159-163 - 163 2007

Research paper (scientific journal), Joint Work, ISSN 09232508

For analyzing the control of energy metabolism in Escherichia coli, we carried out kinetic analyses of glycolytic enzymes purified from the overexpressing clones of E. coli K12 W3110 that were constructed with the vector pCA24N. Phosphoenolpyruvate (PEP) acted as an effective inhibitor of enzymes of the preparatory phase in glycolysis. Glucokinase was potently inhibited by PEP in a competitive manner with respect to ATP: the Ki value for PEP was 0.1 mM. PEP further inhibited phosphoglucoisomerase to a lesser extent, and phosphofructokinase A and aldolase A with 10-fold the Ki values of glucokinase and phosphoglucoisomerase. Glucose is incorporated into E. coli through two pathways: the PTS (PEP-dependent phosphotransferase system) and the glucokinase reaction. PEP, a potent inhibitor of E. coli glucokinase, unlike most eukaryotic hexokinases, can act as a signal molecule controlling glucose uptake and glycolytic flux in cells. © 2006 Elsevier Masson SAS. All rights reserved.

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Simulation of developmental changes in action potentials with ventricular cell models

Itoh, H., Naito, Y. and Tomita, M.

Systems and Synthetic Biology 1 ( 1 ) 11-23 - 23 2007

Research paper (scientific journal), Joint Work, ISSN 18725325

During cardiomyocyte development, early embryonic ventricular cells show spontaneous activity that disappears at a later stage. Dramatic changes in action potential are mediated by developmental changes in individual ionic currents. Hence, reconstruction of the individual ionic currents into an integrated mathematical model would lead to a better understanding of cardiomyocyte development. To simulate the action potential of the rodent ventricular cell at three representative developmental stages, quantitative changes in the ionic currents, pumps, exchangers, and sarcoplasmic reticulum (SR) Ca2+ kinetics were represented as relative activities, which were multiplied by conductance or conversion factors for individual ionic systems. The simulated action potential of the early embryonic ventricular cell model exhibited spontaneous activity, which ceased in the simulated action potential of the late embryonic and neonatal ventricular cell models. The simulations with our models were able to reproduce action potentials that were consistent with the reported characteristics of the cells in vitro. The action potential of rodent ventricular cells at different developmental stages can be reproduced with common sets of mathematical equations by multiplying conductance or conversion factors for ionic currents, pumps, exchangers, and SR Ca 2+ kinetics by relative activities. © Springer Science + Business Media B.V. 2007.

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Visualization of three-way comparisons of omics data

Baran, R., Robert, M., Suematsu, M., Soga, T. and Tomita, M.

BMC Bioinformatics 8 72 2007

Research paper (scientific journal), Joint Work

Background: Density plot visualizations (also referred to as heat maps or color maps) are widely used in different fields including large-scale omics studies in biological sciences. However, the current color-codings limit the visualizations to single datasets or pairwise comparisons. Results: We propose a color-coding approach for the representation of three-way comparisons. The approach is based on the HSB (hue, saturation, brightness) color model. The three compared values are assigned specific hue values from the circular hue range (e.g. red, green, and blue). The hue value representing the three-way comparison is calculated according to the distribution of three compared values. If two of the values are identical and one is different, the resulting hue is set to the characteristic hue of the differing value. If all three compared values are different, the resulting hue is selected from a color gradient running between the hues of the two most distant values (as measured by the absolute value of their difference) according to the relative position of the third value between the two. The saturation of the color representing the three-way comparison reflects the amplitude (or extent) of the numerical difference between the two most distant values according to a scale of interest. The brightness is set to a maximum value by default but can be used to encode additional information about the three-way comparison. Conclusion: We propose a novel color-coding approach for intuitive visualization of three-way comparisons of omics data. © 2007 Baran et al; licensee BioMed Central Ltd.

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