Biomedical subjects

Tero Aittokallio

Publications and source records attributed to Tero Aittokallio.

At least 19 recordsLinked to original sources

PubMed2006

GOlorize: a Cytoscape plug-in for network visualization with Gene Ontology-based layout and coloring.

UNLABELLED: We have implemented a graph layout algorithm that exposes Gene Ontology (GO) class structure on the network nodes. It can be used in conjunction with BiNGO plug-in to Cytoscape, which finds the GO categories over-represented in a given network. Our plug-in, named GOlorize, first highlights the class members with category-specific color-coding and then constructs an enhanced visualization of the network using a class-directed layout algorithm. AVAILABILITY: http://www.cytoscape.org/plugins2.php. SUPPLEMENTARY INFORMATION: Installation instructions and tutorial at http://www.cytoscape.org/plugins/GOlorize/GOlorizeUserGuide.pdf.

Algorithms↗

PubMed2006

Inspiratory flow shape clustering: an automated method to monitor upper airway performance during sleep.

We describe an automated method for monitoring airflow dynamics in the upper airway of a sleeping subject. Its main task is to determine a set of inspiratory flow shape representatives and their relative incidence in a given respiratory airflow material. The flow shape clustering aims at reducing redundant information in the data, and thereby decreases the time needed to score overnight sleep recordings. Compared with previous computer-assisted systems, built on a pre-defined classification of prototype shapes, we require no a priori assumptions of the flow shape clusters to be discovered. The intrinsic flow shape clustering is performed with a modification of the Isodata algorithm, and the K-means clustering is used as a reference in comparison studies. The operation of the method is demonstrated on clinical sleep recordings both from patients with nocturnal breathing disorders and from non-symptomatic individuals. The feasible results obtained in the practical research design suggest that application of clustering algorithms to respiratory airflow measurements could give important insights into the subtle flow shape abnormalities underlying obstructive sleep-disordered breathing.

Algorithms↗

PubMed2006

A statistical score for assessing the quality of multiple sequence alignments.

BACKGROUND: Multiple sequence alignment is the foundation of many important applications in bioinformatics that aim at detecting functionally important regions, predicting protein structures, building phylogenetic trees etc. Although the automatic construction of a multiple sequence alignment for a set of remotely related sequences cause a very challenging and error-prone task, many downstream analyses still rely heavily on the accuracy of the alignments. RESULTS: To address the need for an objective evaluation framework, we introduce a statistical score that assesses the quality of a given multiple sequence alignment. The quality assessment is based on counting the number of significantly conserved positions in the alignment using importance sampling method in conjunction with statistical profile analysis framework. We first evaluate a novel objective function used in the alignment quality score for measuring the positional conservation. The results for the Src homology 2 (SH2) domain, Ras-like proteins, peptidase M13, subtilase and beta-lactamase families demonstrate that the score can distinguish sequence patterns with different degrees of conservation. Secondly, we evaluate the quality of the alignments produced by several widely used multiple sequence alignment programs using a novel alignment quality score and a commonly used sum of pairs method. According to these results, the Mafft strategy L-INS-i outperforms the other methods, although the difference between the Probcons, TCoffee and Muscle is mostly insignificant. The novel alignment quality score provides similar results than the sum of pairs method. CONCLUSION: The results indicate that the proposed statistical score is useful in assessing the quality of multiple sequence alignments.

Algorithms↗

PubMed2006

Th1 response and cytotoxicity genes are down-regulated in cutaneous T-cell lymphoma.

PURPOSE: Increased production of Th2 cytokines characterizes Sezary syndrome, the leukemic form of cutaneous T-cell lymphomas (CTCL). To identify the molecular background and to study whether shared by the most common CTCL subtype, mycosis fungoides, we analyzed the gene expression profiles in both subtypes. EXPERIMENTAL DESIGN: Freshly isolated cells from 30 samples, representing skin, blood, and enriched CD4(+) cell populations of mycosis fungoides and Sezary syndrome, were analyzed with Affymetrix (Santa Clara, CA) oligonucleotide microarrays, quantitative PCR, or immunohistochemistry. The gene expression profiles were combined with findings of comparative genomic hybridization of the same samples to identify chromosomal changes affecting the aberrant gene expression. RESULTS: We identified a set of Th1-specific genes [e.g., TBX21 (T-bet), NKG7, and SCYA5 (RANTES)] to be down-regulated in Sezary syndrome as well as in a proportion of mycosis fungoides samples. In both Sezary syndrome and mycosis fungoides blood samples, the S100P and LIR9 gene expression was up-regulated. In lesional skin, IL7R and CD52 were up-regulated. Integration of comparative genomic hybridization and transcriptomic data identified chromosome arms 1q, 3p, 3q, 4q, 12q, 16p, and 16q as likely targets for new CTCL-associated gene aberrations. CONCLUSIONS: Our findings revealed several new genes involved in CTCL pathogenesis and potential therapeutic targets. Down-regulation of a set of genes involved in Th1 polarization, including the major Th1-polarizing factor, TBX21, was for the first time associated with CTCL. In addition, a plausible explanation for the proliferative response of CTCL cells to locally produced interleukin-7 was revealed.

Cytotoxicity, Immunologic↗

PubMed2006

Graph-based methods for analysing networks in cell biology.

Availability of large-scale experimental data for cell biology is enabling computational methods to systematically model the behaviour of cellular networks. This review surveys the recent advances in the field of graph-driven methods for analysing complex cellular networks. The methods are outlined on three levels of increasing complexity, ranging from methods that can characterize global or local structural properties of networks to methods that can detect groups of interconnected nodes, called motifs or clusters, potentially involved in common elementary biological functions. We also briefly summarize recent approaches to data integration and network inference through graph-based formalisms. Finally, we highlight some challenges in the field and offer our personal view of the key future trends and developments in graph-based analysis of large-scale datasets.

Artificial Intelligence↗

PubMed2006

Improving identification of differentially expressed genes by integrative analysis of Affymetrix and Illumina arrays.

Together with the widely used Affymetrix microarrays, the recently introduced Illumina platform has become a cost-effective alternative for genome-wide studies. To efficiently use data from both array platforms, there is a pressing need for methods that allow systematic integration of multiple datasets, especially when the number of samples is small. To address these needs, we introduce a meta-analytic procedure for combining Affymetrix and Illumina data in the context of detecting differentially expressed genes between the platforms. We first investigate the effect of different expression change estimation procedures within the platforms on the agreement of the most differentially expressed genes. Using the best estimation methods, we then show the benefits of the integrative analysis in producing reproducible results across bootstrap samples. In particular, we demonstrate its biological relevance in identifying small but consistent changes during T helper 2 cell differentiation.

Cell Differentiation↗

PubMed2006

Automated pattern ranking in differential display data analysis.

Gene expression analysis by differential display (DD) is limited by the labor-intensive visual evaluation of the electrophoretic data traces. We describe a flexible method for computer-assisted ranking of expression patterns in data from DD experiments. The method is based on a pairwise alignment and comparison of the quantitative trace data with respect to specific expression patterns defined by the investigator. The observed patterns are ranked according to a score value that identifies the most potential findings to be confirmed visually instead of the vast amount of original results. This two-step approach, enabled by the efficient computer algorithm for gene expression pattern comparison, will increase the percentage of true-positive findings chosen for the tedious downstream processing, while minimizing the cost and labor involved in large scale DD data analysis.

Algorithms↗

PubMed2005

Improving missing value estimation in microarray data with gene ontology.

MOTIVATION: Gene expression microarray experiments produce datasets with frequent missing expression values. Accurate estimation of missing values is an important prerequisite for efficient data analysis as many statistical and machine learning techniques either require a complete dataset or their results are significantly dependent on the quality of such estimates. A limitation of the existing estimation methods for microarray data is that they use no external information but the estimation is based solely on the expression data. We hypothesized that utilizing a priori information on functional similarities available from public databases facilitates the missing value estimation. RESULTS: We investigated whether semantic similarity originating from gene ontology (GO) annotations could improve the selection of relevant genes for missing value estimation. The relative contribution of each information source was automatically estimated from the data using an adaptive weight selection procedure. Our experimental results in yeast cDNA microarray datasets indicated that by considering GO information in the k-nearest neighbor algorithm we can enhance its performance considerably, especially when the number of experimental conditions is small and the percentage of missing values is high. The increase of performance was less evident with a more sophisticated estimation method. We conclude that even a small proportion of annotated genes can provide improvements in data quality significant for the eventual interpretation of the microarray experiments. AVAILABILITY: Java and Matlab codes are available on request from the authors. SUPPLEMENTARY MATERIAL: Available online at http://users.utu.fi/jotatu/GOImpute.html.

Algorithms↗

PubMed2005

Integrating probe-level expression changes across generations of Affymetrix arrays.

There is an urgent need for bioinformatic methods that allow integrative analysis of multiple microarray data sets. While previous studies have mainly concentrated on reproducibility of gene expression levels within or between different platforms, we propose a novel meta-analytic method that takes into account the vast amount of available probe-level information to combine the expression changes across different studies. We first show that the comparability of relative expression changes and the consistency of differentially expressed genes between different Affymetrix array generations can be considerably improved by determining the expression changes at the probe-level and by considering the latest information on probe-level sequence matching instead of the probe annotations provided by the manufacturer. With the improved probe-level expression change estimates, data from different generations of Affymetrix arrays can be combined more effectively. This will allow for the full exploitation of existing results when designing and analyzing new experiments.

Animals↗

PubMed2005

Quality classification of tandem mass spectrometry data.

UNLABELLED: Peptide identification by tandem mass spectrometry is an important tool in proteomic research. Powerful identification programs exist, such as SEQUEST, ProICAT and Mascot, which can relate experimental spectra to the theoretical ones derived from protein databases, thus removing much of the manual input needed in the identification process. However, the time-consuming validation of the peptide identifications is still the bottleneck of many proteomic studies. One way to further streamline this process is to remove those spectra that are unlikely to provide a confident or valid peptide identification, and in this way to reduce the labour from the validation phase. RESULTS: We propose a prefiltering scheme for evaluating the quality of spectra before the database search. The spectra are classified into two classes: spectra which contain valuable information for peptide identification and spectra that are not derived from peptides or contain insufficient information for interpretation. The different spectral features developed for the classification are tested on a real-life material originating from human lymphoblast samples and on a standard mixture of 9 proteins, both labelled with the ICAT-reagent. The results show that the prefiltering scheme efficiently separates the two spectra classes.

Algorithms↗

PubMed2005

Non-invasive respiratory monitoring during wakefulness and sleep in pre- and postmenopausal women.

Menopause and aging cause hormonal changes with respiratory consequences. The aim of the present study was to investigate the physiological changes in respiration during wakefulness and sleep across menopause in non-patient population using non-invasive measurements of blood and tissue gases. The arterial oxyhemoglobin saturation (SaO2), heart rate, end-tidal partial carbon dioxide tension (EtCO2) and transcutaneous partial carbon dioxide tension (TcCO2) were measured during wakefulness and sleep in thirteen pairs of BMI-matched pre- and postmenopausal women. Postmenopausal women had lower SaO2 during sleep than during wakefulness, whereas premenopausal women maintained their wakefulness SaO2 levels also during sleep. EtCO2 levels did not change either between wakefulness and sleep or between premenopausal and postmenopausal groups. TcCO2 levels increased from wakefulness to sleep in both groups and the increase was greater in the postmenopausal group. The impact of sleep on the non-invasive measurements of blood and tissue gases is stronger in postmenopausal women.

Adult↗

PubMed2005

Medroxyprogesterone improves nocturnal breathing in postmenopausal women with chronic obstructive pulmonary disease.

BACKGROUND: Progestins as respiratory stimulants in chronic obstructive pulmonary disease (COPD) have been investigated in males and during wakefulness. However, sleep and gender may influence therapeutic responses. We investigated the effects of a 2-week medroxyprogesterone acetate (MPA) therapy on sleep and nocturnal breathing in postmenopausal women. METHODS: A single-blind placebo-controlled trial was performed in 15 postmenopausal women with moderate to severe COPD. A 12-week trial included 2-week treatment periods with placebo and MPA (60 mg/d/14 days). All patients underwent a polysomnography with monitoring of SaO2 and transcutaneous PCO2 (tcCO2) at baseline, with placebo, with medroxyprogesterone acetate (MPA 60 mg/d/14 days), and three and six weeks after cessation of MPA. RESULTS: Thirteen patients completed the trial. At baseline, the average +/- SD of SaO2 mean was 90.6 +/- 3.2 % and the median of SaO2 nadir 84.8 % (interquartile range, IQR 6.1). MPA improved them by 1.7 +/- 1.6 %-units (95 % confidence interval (CI) 0.56, 2.8) and by 3.9 %-units (IQR 4.9; 95% CI 0.24, 10.2), respectively. The average of tcCO2 median was 6.0 +/- 0.9 kPa and decreased with MPA by 0.9 +/- 0.5 kPa (95% CI -1.3, -0.54). MPA improved SaO2 nadir and tcCO2 median also during REM sleep. Three weeks after cessation of MPA, the SaO2 mean remained 1.4 +/- 1.8 %-units higher than at baseline, the difference being not significant (95% CI -0.03, 2.8). SaO2 nadir was 2.7 %-units (IQR 4.9; 95% CI 0.06, 18.7) higher than at baseline. Increases in SaO2 mean and SaO2 nadir during sleep with MPA were inversely associated with baseline SaO2 mean (r = -0.70, p = 0.032) and baseline SaO2 nadir (r = -0.77, p = 0.008), respectively. Treatment response in SaO2 mean, SaO2 nadir and tcCO2 levels did not associate with pack-years smoked, age, BMI, spirometric results or sleep variables. CONCLUSION: MPA-induced respiratory improvement in postmenopausal women seems to be consistent and prolonged. The improvement was greater in patients with lower baseline SaO2 values. Long-term studies in females are warranted.

Aged↗

PubMed2005

Sleep quality, daytime sleepiness and fasting insulin levels in women with chronic obstructive pulmonary disease.

STUDY OBJECTIVES: To test the clinical observations that patients with chronic obstructive pulmonary disease (COPD) have impaired sleep quality without excessive daytime sleepiness (EDS), and to analyse the aetiological factors. PARTICIPANTS: Fifteen non-diabetic postmenopausal women with moderate to severe COPD and 20 community dwelling age-matched control women. MEASUREMENTS AND RESULTS: Patients completed questionnaires, had a polysomnography and blood tests. Controls filled in the questionnaires. In the Basic Nordic Sleep Questionnaire, the average (+/-sd) scores for sleepiness (9.9+/-3.0 in patients vs. 7.6+/-3.2 in controls, P = 0.025, test range 4-20) and insomnia (18.3+/-3.4 vs. 16.6+/-4.4, P = 123, test range 7-35) were low. Although 53% had a good night's sleep seldom or never and 70% slept restlessly, only 33% felt tired in the mornings. Controls reported better sleep quality, less tiredness and sleepiness. With polysomnography, the total sleep time was 4h 41 min +/-1h 20 min in patients. Sleep was fragmented, the proportion of stage 1 sleep high and rapid eye movement (REM) latency delayed. Sleepiness correlated with fasting serum insulin levels (r = 0.59, P = 0.027) and body movements (r = 0.52, P = 0.047). In stepwise linear regression analyses, sleepiness was positively associated with insulin levels (P = 0.025) but not with body movements. Insulin explained 38.0% of the variance in the sleepiness score, when adjusted for body mass index (BMI). CONCLUSIONS: Despite short and fragmented sleep, non-diabetic patients with COPD did not have marked EDS. An association between fasting insulin and sleepiness suggests that insulin resistance is involved in EDS.

Aged↗

PubMed2005

A comparative evaluation of software for the analysis of liquid chromatography-tandem mass spectrometry data from isotope coded affinity tag experiments.

The options available for processing quantitative data from isotope coded affinity tag (ICAT) experiments have mostly been confined to software specific to the instrument of acquisition. However, recent developments with data format conversion have subsequently increased such processing opportunities. In the present study, data sets from ICAT experiments, analysed with liquid chromatography/tandem mass spectrometry (MS/MS), using an Applied Biosystems QSTAR Pulsar quadrupole-TOF mass spectrometer, were processed in triplicate using separate mass spectrometry software packages. The programs Pro ICAT, Spectrum Mill and SEQUEST with XPRESS were employed. Attention was paid towards the extent of common identification and agreement of quantitative results, with additional interest in the flexibility and productivity of these programs. The comparisons were made with data from the analysis of a specifically prepared test mixture, nine proteins at a range of relative concentration ratios from 0.1 to 10 (light to heavy labelled forms), as a known control, and data selected from an ICAT study involving the measurement of cytokine induced protein expression in human lymphoblasts, as an applied example. Dissimilarities were detected in peptide identification that reflected how the associated scoring parameters favoured information from the MS/MS data sets. Accordingly, there were differences in the numbers of peptides and protein identifications, although from these it was apparent that both confirmatory and complementary information was present. In the quantitative results from the three programs, no statistically significant differences were observed.

Algorithms↗

PubMed2004

Statistical methods for identifying conserved residues in multiple sequence alignment.

The assessment of residue conservation in a multiple sequence alignment is a central issue in bioinformatics. Conserved residues and regions are used to determine structural and functional motifs or evolutionary relationships between the sequences of a multiple sequence alignment. For this reason, residue conservation is a valuable measure for database and motif search or for estimating the quality of alignments. In this paper, we present statistical methods for identifying conserved residues in multiple sequence alignments. While most earlier studies examine the positional conservation of the alignment, we focus on the detection of individual conserved residues at a position. The major advantages of multiple comparison methods originate from their ability to select conserved residues simultaneously and to consider the variability of the residue estimates. Large-scale simulations were used for the comparative analysis of the methods. Practical performance was studied by comparing the structurally and functionally important residues of Src homology 2 (SH2) domains to the assignments of the conservation indices. The applicability of the indices was also compared in three additional protein families comprising different degrees of entropy and variability in alignment positions. The results indicate that statistical multiple comparison methods are sensitive and reliable in identifying conserved residues.

Journal Article↗

PubMed2003

Efficient estimation of emission probabilities in profile hidden Markov models.

MOTIVATION: Profile hidden Markov models provide a sensitive method for performing sequence database search and aligning multiple sequences. One of the drawbacks of the hidden Markov model is that the conserved amino acids are not emphasized, but signal and noise are treated equally. For this reason, the number of estimated emission parameters is often enormous. Focusing the analysis on conserved residues only should increase the accuracy of sequence database search. RESULTS: We address this issue with a new method for efficient emission probability (EEP) estimation, in which amino acids are divided into effective and ineffective residues at each conserved alignment position. A practical study with 20 protein families demonstrated that the EEP method is capable of detecting family members from other proteins with sensitivity of 98% and specificity of 99% on the average, even if the number of free emission parameters was decreased to 15% of the original. In the database search for TIM barrel sequences, EEP recognizes the family members nearly as accurately as HMMER or Blast, but the number of false positive sequences was significantly less than that obtained with the other methods. AVAILABILITY: The algorithms written in C language are available on request from the authors.

Algorithms↗

PubMed2003

Identification of novel genes regulated by IL-12, IL-4, or TGF-beta during the early polarization of CD4+ lymphocytes.

Th1 and Th2 cells arise from a common precursor cell in response to triggering through the TCR and cytokine receptors for IL-12 or IL-4. This leads to activation of complex signaling pathways, which are not known in detail. Disturbances in the balance between type 1 and type 2 responses can lead to certain immune-mediated diseases. Thus, it is important to understand how Th1 and Th2 cells are generated. To clarify the mechanisms as to how IL-12 and IL-4 induce Th1 and Th2 differentiation and how TGF-beta can inhibit this process, we have used oligonucleotide arrays to examine the early polarization of Th1 and Th2 cells in the presence and absence of TGF-beta. In addition to genes previously implicated in the process, we have identified 20 genes with various known and unknown functions not previously associated with Th1/2 polarization. We have also further determined which genes are targets of IL-12, IL-4, and TGF-beta regulation in the cells induced to polarize to Th1 and Th2 directions. Interestingly, a subset of the genes was coregulated by IL-12 or IL-4 and TGF-beta. Among these genes are candidates that may modulate the balance between Th1 and Th2 responses.

Biomarkers↗

PubMed2003

Prediction of inspiratory flow shapes during sleep with a mathematic model of upper airway forces.

STUDY OBJECTIVES: To predict the airflow dynamics during sleep using a mathematic model that incorporates a number of static and dynamic upper airway forces, and to compare the numerical results to clinical flow data recorded from patients with sleep-disordered breathing on and off various treatment options. DESIGN: Upper airway performance was modeled in virtual subjects characterized by parameter settings that describe common combinations of risk factors predisposing to upper airway collapse during sleep. The treatments effect were induced by relevant changes of the initial parameter values. SETTING: Computer simulations at our website (http://www.utu.fi/ml/sovmat/bio/). PARTICIPANTS: Risk factors considered in the simulation settings were sex, obesity, pharyngeal collapsibility, and decreased phasic activity of pharyngeal muscles. INTERVENTIONS: The effects of weight loss, pharyngeal surgery, nasal continuous positive airway pressure, and respiratory stimulation on the inspiratory flow characteristics were tested with the model. MEASUREMENTS AND RESULTS: Numerical predictions were investigated by means of 3 measurable inspiratory airflow characteristics: initial slope, total volume, and flow shape. The model was able to reproduce the inspiratory flow shape characteristics that have previously been described in the literature. Simulation results also supported the observations that a multitude of factors underlie the pharyngeal collapse and, therefore, certain medical therapies that are effective in some conditions may prove ineffective in others. CONCLUSIONS: A mathematic model integrating the current knowledge of upper airway physiology is able to predict individual treatment responses. The model provides a framework for designing novel and potentially feasible treatment alternatives for sleep-disordered breathing.

Arousal↗