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At least 199 records · Page 11Linked to original sources
PubMed2005

Classification of a large microarray data set: algorithm comparison and analysis of drug signatures.

A large gene expression database has been produced that characterizes the gene expression and physiological effects of hundreds of approved and withdrawn drugs, toxicants, and biochemical standards in various organs of live rats. In order to derive useful biological knowledge from this large database, a variety of supervised classification algorithms were compared using a 597-microarray subset of the data. Our studies show that several types of linear classifiers based on Support Vector Machines (SVMs) and Logistic Regression can be used to derive readily interpretable drug signatures with high classification performance. Both methods can be tuned to produce classifiers of drug treatments in the form of short, weighted gene lists which upon analysis reveal that some of the signature genes have a positive contribution (act as "rewards" for the class-of-interest) while others have a negative contribution (act as "penalties") to the classification decision. The combination of reward and penalty genes enhances performance by keeping the number of false positive treatments low. The results of these algorithms are combined with feature selection techniques that further reduce the length of the drug signatures, an important step towards the development of useful diagnostic biomarkers and low-cost assays. Multiple signatures with no genes in common can be generated for the same classification end-point. Comparison of these gene lists identifies biological processes characteristic of a given class.

Algorithms↗
PubMed2005

Virtual endoscopic visualization of the colon by shape-scale signatures.

We developed a new visualization method for virtual endoscopic examination of computed tomographic (CT) colonographic data by use of shape-scale analysis. The method provides each colonic structure of interest with a unique color, thereby facilitating rapid diagnosis of the colon. Two shape features, called the local shape index and curvedness, are used for defining the shape-scale spectrum. When we map the shape index and curvedness values within CT colonographic data to the shape-scale spectrum, specific types of colonic structures are represented by unique characteristic signatures in the spectrum. The characteristic signatures of specific types of lesions can be determined by use of computer-simulated lesions or by use of clinical data sets subjected to a computerized detection scheme. The signatures are used for defining a two-dimensional color map by assignment of a unique color to each signature region. The method was evaluated visually by use of computer-simulated lesions and clinical CT colonographic data sets, as well as by an evaluation of the human observer performance in the detection of polyps without and with the use of the color maps. The results indicate that the coloring of the colon yielded by the shape-scale color maps can be used for differentiating among the chosen colonic structures. Moreover, the results indicate that the use of the shape-scale color maps can improve the performance of radiologists in the detection of polyps in CT colonography.

Algorithms↗
PubMed2003

Detection of spectral signatures in multispectral MR images for classification.

This paper presents a new spectral signature detection approach to magnetic resonance (MR) image classification. It is called constrained energy minimization (CEM) method, which is derived from the minimum variance distortionless response in passive sensor array processing. It considers a bank of spectral channels as an array of sensors where each spectral channel represents a sensor and object spectral signature in multispectral MR images are viewed as signals impinging upon the array. The strength of the CEM lies on its ability in detection of spectral signatures of interest without knowing image background. The detected spectral signatures are then used for classification. The CEM makes use of a finite impulse response (FIR) filter to linearly constrain a desired object while minimizing interfering effects caused by other unknown signal sources. Unlike most spatial-based classification techniques, the proposed CEM takes advantage of spectral characteristics to achieve object detection and classification. A series of experiments is conducted and compared with the commonly used c-means method for performance evaluation. The results show that the CEM method is a promising and effective spectral technique for MR image classification.

Algorithms↗
PubMedDate not supplied

Graph signatures for visual analytics.

We present a visual analytics technique to explore graphs using the concept of a data signature. A data signature, in our context, is a multidimensional vector that captures the local topology information surrounding each graph node. Signature vectors extracted from a graph are projected onto a low-dimensional scatterplot through the use of scaling. The resultant scatterplot, which reflects the similarities of the vectors, allows analysts to examine the graph structures and their corresponding real-life interpretations through repeated use of brushing and linking between the two visualizations. The interpretation of the graph structures is based on the outcomes of multiple participatory analysis sessions with intelligence analysts conducted by the authors at the Pacific Northwest National Laboratory. The paper first uses three public domain data sets with either well-known or obvious features to explain the rationale of our design and illustrate its results. More advanced examples are then used in a customized usability study to evaluate the effectiveness and efficiency of our approach. The study results reveal not only the limitations and weaknesses of the traditional approach based solely on graph visualization, but also the advantages and strengths of our signature-guided approach presented in the paper.

Algorithms↗
PubMed2005

Routine expression profiling of microarray gene signatures in acute leukaemia by real-time PCR of human bone marrow.

Cancer subtype diagnosis using microarray signatures has the potential to transform pathological diagnosis but the routine measurement of genes signatures remains difficult. Reverse transcription polymerase chain reaction (RT-PCR) measurement of Indicator genes for acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) was used to determine gene signatures. Bone marrow (BM) mononuclear cells were sorted into total, CD34(+) and CD34(-) fractions, and mRNAs globally amplified from each fraction using polyA PCR. The expression profile of the 17 top-ranked genes distinguishing AML and ALL were measured by RT-PCR in five ALL, 26 AML, 12 AML remission, four chronic myeloid leukaemia (CML) and nine morphologically normal BM samples. All but two of the genes measured showed similar expression in AML and ALL to that reported previously. Specifically, c-MYB (P </= 0.04) was significantly increased in ALL in the total fraction, whilst HOXA9 (P </= 0.19) and cystatin c (P </= 0.01) were increased in AML in the CD34(+) and CD34(-) fractions, respectively. c-MYB, hSNF2, RBAP48, HKRT-1, LYN, CD33, Adipsin and HOXA9 were increased in AML compared with remission AML, indicating an ability to determine disease activity. The method used is simple, sensitive and robust, enabling routine clinical use, and it can also be extended to other tumours types with gene signatures.

Acute Disease↗
PubMed2002

Surf-generated noise signatures: a comparison of plunging and spilling breakers.

Range-time-frequency distributions of surf-generated noise were measured within the surf zone during the SandyDuck'97 experiment at Duck, NC. A 24-phone, 138-m, bottom-mounted, linear array located along a line perpendicular to the shore at a depth of 1 to 3 m recorded the surf-generated noise. Concurrent video measurements of the location, size, and time-evolution of the individual breaking waves directly above the array were made from a nearby 43-m tower. Source level spectra are obtained by using a modified fast field program to account for water column and geoacoustic propagation from the distributed source region to an individual hydrophone. The length, location, and orientation of the leading edge of breakers are tracked in time from rectified video images. It is observed that the source levels from spilling breakers are lower (approximately 5-10 dB) than those produced by plunging breakers that occurred during the same time period. Plunging breakers generated time-frequency signatures with a sharp onset while spilling breakers' signatures had a gradual low-frequency precursor. Range-time signatures of plunging breakers indicate a burst of acoustic energy while spilling breakers' signatures depict sound being generated over a longer time period with the source region moving with the breaking surface wave.

Journal Article↗
PubMed1988

The acoustic signature for intelligibility test words.

As part of a research program that aims to develop an explicit acoustic basis for a single-word intelligibility test, an initial attempt to characterize the formant trajectories and segment durations of seven test words produced by 30 normal speakers is described. These characterizations are referred to as "acoustic signatures." The data indicate that: (1) formant trajectories show two sex effects, namely, that females are more variable as a group than males and tend to have greater slopes for the transitional segment of the second-formant trajectories and that these effects are consistent across words; (2) Bark transformations of the frequency data do not seem to eliminate the interspeaker differences in formant trajectories, nor do they eliminate either of the sex effects described above; and (3) segment durations have different variabilities depending on the syllabic structure of the word; no sex effect was noted here. The discussion focuses on the appropriate form for the acoustic signatures, as well as factors that should be considered in selecting words for signature development. To demonstrate the potential application of these data, formant trajectory and segment duration data from 18 speakers with amyotrophic lateral sclerosis and varying degrees of dysarthria are compared to the acoustic signature for the word wax.

Aged↗
PubMed1999

Correlation of 16S ribosomal DNA signature sequences with temperature-dependent growth rates of mesophilic and psychrotolerant strains of the Bacillus cereus group.

Sequences of the 16S ribosomal DNA (rDNA) from psychrotolerant and mesophilic strains of the Bacillus cereus group revealed signatures which were specific for these two thermal groups of bacteria. Further analysis of the genomic DNA from a wide range of food and soil isolates showed that B. cereus group strains have between 6 and 10 copies of 16S rDNA. Moreover, a number of these environmental strains have both rDNA operons with psychrotolerant signatures and rDNA operons with mesophilic signatures. The ability of these isolates to grow at low temperatures correlates with the prevalence of rDNA operons with psychrotolerant signatures, indicating specific nucleotides within the 16S rRNA to play a role in psychrotolerance.

Bacillus↗
PubMed2004

Protein structure alignment and fast similarity search using local shape signatures.

We present a new method for conducting protein structure similarity searches, which improves on the efficiency of some existing techniques. Our method is grounded in the theory of differential geometry on 3D space curve matching. We generate shape signatures for proteins that are invariant, localized, robust, compact, and biologically meaningful. The invariancy of the shape signatures allows us to improve similarity searching efficiency by adopting a hierarchical coarse-to-fine strategy. We index the shape signatures using an efficient hashing-based technique. With the help of this technique we screen out unlikely candidates and perform detailed pairwise alignments only for a small number of candidates that survive the screening process. Contrary to other hashing based techniques, our technique employs domain specific information (not just geometric information) in constructing the hash key, and hence, is more tuned to the domain of biology. Furthermore, the invariancy, localization, and compactness of the shape signatures allow us to utilize a well-known local sequence alignment algorithm for aligning two protein structures. One measure of the efficacy of the proposed technique is that we were able to perform structure alignment queries 36 times faster (on the average) than a well-known method while keeping the quality of the query results at an approximately similar level.

Algorithms↗
PubMed1995

Authentication of digital medical images with digital signature technology.

PURPOSE: To determine whether digital signature technology (DST) can authenticate digital medical images to the same level of authenticity required for interbank electronic transfer of funds. MATERIALS AND METHODS: Message digests were computed for two magnetic resonance images that differed only by the value of a single bit. RSA (Rivest, Shamir, and Adleman) public key cryptography was used to encrypt each message digest to form a digital signature for each image, a process analogous to the established use of RSA DST for electronic funds transfer. The process was then reversed to authenticate the original image from its digital signature. RESULTS: Although the images differed by less than 0.000095%, their message digests differed at 94% of their characters. The digital signature of the original image proved that it was authentic and that the altered image was not authentic. CONCLUSION: RSA DST can establish the authenticity of images to at least the level of confidence required for interbank electronic transfer of funds.

Algorithms↗
PubMed2005

A gene expression signature of genetic instability in colon cancer.

Genetic instability plays a central role in the development and progression of human cancer. Two major classes of genetic instability, microsatellite instability (MSI) and chromosome instability (microsatellite stable; MSS), are best understood in the context of colon cancer, where MSI tumors represent approximately 15% of cases, and compared with MSS tumors, more often arise in the proximal colon and display favorable clinical outcome. To further explore molecular differences, we profiled gene expression in a set of 18 colon cancer cell lines using cDNA microarrays representing approximately 21,000 different genes. Supervised analysis identified a robust expression signature distinguishing MSI and MSS samples. As few as eight genes predicted with high accuracy the underlying genetic instability in the original and in three independent sample sets, comprising 13 colon cancer cell lines, 61 colorectal tumors, and 87 gastric tumors. Notably, the MSI signature was retained despite genetically correcting the underlying instability, suggesting the signature reflects a legacy of the tumor having arisen from MSI, rather than sensing the ongoing state of MSI. Our findings support a model in which MSI and MSS preferentially target different genes and pathways in cancer. Further, among the MSI signature genes, our findings implicate a role of elevated metallothionein expression in the clinical behavior of MSI cancers.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.

Women who have their first child early in life have a substantially lower lifetime risk of breast cancer. The mechanism for this is unknown. Similar to humans, rats exhibit parity-induced protection against mammary tumorigenesis. To explore the basis for this phenomenon, we identified persistent pregnancy-induced changes in mammary gene expression that are tightly associated with protection against tumorigenesis in multiple inbred rat strains. Four inbred rat strains that exhibit marked differences in their intrinsic susceptibilities to carcinogen-induced mammary tumorigenesis were each shown to display significant protection against methylnitrosourea-induced mammary tumorigenesis following treatment with pregnancy levels of estradiol and progesterone. Microarray expression profiling of parous and nulliparous mammary tissue from these four strains yielded a common 70-gene signature. Examination of the genes constituting this signature implicated alterations in transforming growth factor-beta signaling, the extracellular matrix, amphiregulin expression, and the growth hormone/insulin-like growth factor I axis in pregnancy-induced alterations in breast cancer risk. Notably, related molecular changes have been associated with decreased mammographic density, which itself is strongly associated with decreased breast cancer risk. Our findings show that hormone-induced protection against mammary tumorigenesis is widely conserved among divergent rat strains and define a gene expression signature that is tightly correlated with reduced mammary tumor susceptibility as a consequence of a normal developmental event. Given the conservation of this signature, these pathways may contribute to pregnancy-induced protection against breast cancer.

Amphiregulin↗
PubMed2006

Identification of a PAX-FKHR gene expression signature that defines molecular classes and determines the prognosis of alveolar rhabdomyosarcomas.

Alveolar rhabdomyosarcomas (ARMS) are aggressive soft-tissue sarcomas affecting children and young adults. Most ARMS tumors express the PAX3-FKHR or PAX7-FKHR (PAX-FKHR) fusion genes resulting from the t(2;13) or t(1;13) chromosomal translocations, respectively. However, up to 25% of ARMS tumors are fusion negative, making it unclear whether ARMS represent a single disease or multiple clinical and biological entities with a common phenotype. To test to what extent PAX-FKHR determine class and behavior of ARMS, we used oligonucleotide microarray expression profiling on 139 primary rhabdomyosarcoma tumors and an in vitro model. We found that ARMS tumors expressing either PAX-FKHR gene share a common expression profile distinct from fusion-negative ARMS and from the other rhabdomyosarcoma variants. We also observed that PAX-FKHR expression above a minimum level is necessary for the detection of this expression profile. Using an ectopic PAX3-FKHR and PAX7-FKHR expression model, we identified an expression signature regulated by PAX-FKHR that is specific to PAX-FKHR-positive ARMS tumors. Data mining for functional annotations of signature genes suggested a role for PAX-FKHR in regulating ARMS proliferation and differentiation. Cox regression modeling identified a subset of genes within the PAX-FKHR expression signature that segregated ARMS patients into three risk groups with 5-year overall survival estimates of 7%, 48%, and 93%. These prognostic classes were independent of conventional clinical risk factors. Our results show that PAX-FKHR dictate a specific expression signature that helps define the molecular phenotype of PAX-FKHR-positive ARMS tumors and, because it is linked with disease outcome in ARMS patients, determine tumor behavior.

Biomarkers, Tumor↗
PubMed2005

Transcriptional signature of Ecteinascidin 743 (Yondelis, Trabectedin) in human sarcoma cells explanted from chemo-naive patients.

Ecteinascidin 743 (ET-743; Yondelis, Trabectedin) is a marine anticancer agent that induces long-lasting objective remissions and tumor control in a subset of patients with pretreated/resistant soft-tissue sarcoma. Drug-induced tumor control is achievable in 22% of such patients, but there is no clear indication of the molecular features correlated with clinical sensitivity/resistance to ET-743. Nine low-passage, soft-tissue sarcoma cell lines, explanted from chemo-naive patients with different patterns of sensitivity, have been profiled with a cDNA microarray containing 6,700 cancer-related genes. The molecular signature of these cell lines was analyzed at baseline and at four different times after ET-743 exposure. The association of levels of TP53 mutation and TP73 expression with ET-743 sensitivity and cell cycle kinetics after treatment was also analyzed. Gene expression profile analysis revealed up-regulation of 86 genes and down-regulation of 244 genes in response to ET-743. The ET-743 gene expression signature identified a group of genes related with cell cycle control, stress, and DNA-damage response (JUNB, ATF3, CS-1, SAT, GADD45B, and ID2) that were up-regulated in all the cell lines studied. The transcriptional signature 72 hours after ET-743 administration, associated with ET-743 sensitivity, showed a more efficient induction of genes involved in DNA-damage response and apoptosis, such as RAD17, BRCA1, PAR4, CDKN1A, and P53DINP1, in the sensitive cell line group. The transcriptional signature described here may lead to the identification of ET-743 downstream mediators and transcription regulators and the proposal of strategies by which ET-743-sensitive tumors may be identified.

Antineoplastic Agents, Alkylating↗
PubMed2004

Comparative expressed sequence hybridization studies of hairy cell leukemia show uniform expression profile and imprint of spleen signature.

Comparative expressed sequence hybridization (CESH) to chromosomes is a recently introduced technique that identifies chromosomal regions corresponding to a differential gene expression. This technique is analogous to comparative genomic hybridization (CGH) that detects genomic imbalances. We applied CESH for the study of hairy cell leukemia (HCL), a disorder with a largely unknown expression profile. Twelve HCL cases with spleen involvement were investigated by CESH and CGH. While the latter analysis identified only a few nonrecurrent genomic imbalances, CESH showed a consistent expression profile in all HCL cases. In addition, pairing normal spleen with normal lymph node, a "spleen signature" was established by CESH. This signature most likely reflects the expression profile of spleen-specific components, such as the sinusoidal lining cells from the red pulp and the marginal zone B cells from the white pulp. Imprint of the spleen signature was found in the HCL expression profile, suggesting that HCL may originate from a particular B-cell subset present in these splenic components. Besides pairing HCL with normal lymph node and spleen, we identified an "HCL signature" comprising several chromosome regions with altered expression. The most significantly underexpressed regions include 3p24, 3p21, 3q13.3-q22, 4p16, 11q23, 14q22-q24, 15q21-q22, 15q24-q25, and 17q22-q24; and 13q31 and Xq13.3-q21 were the most significantly overexpressed. These regions possibly harbor genes related to the biology and the pathogenesis of HCL. Their identification warrants further molecular investigations.

Cell Line, Tumor↗
PubMed2006

The reach of the genome signature in prokaryotes.

BACKGROUND: With the increased availability of sequenced genomes there have been several initiatives to infer evolutionary relationships by whole genome characteristics. One of these studies suggested good congruence between genome synteny, shared gene content, 16S ribosomal DNA identity, codon usage and the genome signature in prokaryotes. Here we rigorously test the phylogenetic signal of the genome signature, which consists of the genome-specific relative frequencies of dinucleotides, on 334 sequenced prokaryotic genome sequences. RESULTS: Intrageneric comparisons show that in general the genomic dissimilarity scores are higher than in intraspecific comparisons, in accordance with the suggested phylogenetic signal of the genome signature. Exceptions to this trend, (Bartonella spp., Bordetella spp., Salmonella spp. and Yersinia spp.), which have low average intrageneric genomic dissimilarity scores, suggest that members of these genera might be considered the same species. On the other hand, high genomic dissimilarity values for intraspecific analyses suggest that in some cases (e.g. Prochlorococcus marinus, Pseudomonas fluorescens, Buchnera aphidicola and Rhodopseudomonas palustris) different strains from the same species may actually represent different species. Comparing 16S rDNA identity with genomic dissimilarity values corroborates the previously suggested trend in phylogenetic signal, albeit that the dissimilarity values only provide low resolution. CONCLUSION: The genome signature has a distinct phylogenetic signal, independent of individual genetic marker genes. A reliable phylogenetic clustering cannot be based on dissimilarity values alone, as bootstrapping is not possible for this parameter. It can however be used to support or refute a given phylogeny and resulting taxonomy.

Bacteria↗
PubMed2002

Pervasive properties of the genomic signature.

BACKGROUND: The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome. Both the causes and the functional significance of this phenomenon could be illuminated by determining if it persists on smaller scales. The profile is computed from the base step "odds ratios" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling). Analysis is carried out on 22 sequences, representing 19 species and comprised of about 53 million bases all together, to assess stability of the signature in windows ranging in size from 50 kilobases down to 125 bases. RESULTS: Dinucleotide relative abundance distance from the global signature is computed locally for all non-overlapping windows on each sequence. These distances are log-normally distributed with nearly constant variance and with means that tend to zero slower than reciprocal square root of window size. The mean distance within genomes is larger for protist, plant, and human chromosomes, and smaller for archaea, bacteria, and yeast, for any window size. CONCLUSIONS: The imprint of the global signature is locally pervasive on all scales considered in the sequences (either genomes or chromosomes) that were scanned.

Journal Article↗
PubMed2005

An acquisition account of genomic islands based on genome signature comparisons.

BACKGROUND: Recent analyses of prokaryotic genome sequences have demonstrated the important force horizontal gene transfer constitutes in genome evolution. Horizontally acquired sequences are detectable by, among others, their dinucleotide composition (genome signature) dissimilarity with the host genome. Genomic islands (GIs) comprise important and interesting horizontally transferred sequences, but information about acquisition events or relatedness between GIs is scarce. In Vibrio vulnificus CMCP6, 10 and 11 GIs have previously been identified in the sequenced chromosomes I and II, respectively. We assessed the compositional similarity and putative acquisition account of these GIs using the genome signature. For this analysis we developed a new algorithm, available as a web application. RESULTS: Of 21 GIs, VvI-1 and VvI-10 of chromosome I have similar genome signatures, and while artificially divided due to a linear annotation, they are adjacent on the circular chromosome and therefore comprise one GI. Similarly, GIs VvI-3 and VvI-4 of chromosome I together with the region between these two islands are compositionally similar, suggesting that they form one GI (making a total of 19 GIs in chromosome I + chromosome II). Cluster analysis assigned the 19 GIs to 11 different branches above our conservative threshold. This suggests a limited number of compositionally similar donors or intragenomic dispersion of ancestral acquisitions. Furthermore, 2 GIs of chromosome II cluster with chromosome I, while none of the 19 GIs group with chromosome II, suggesting an unidirectional dispersal of large anomalous gene clusters from chromosome I to chromosome II. CONCLUSION: From the results, we infer 10 compositionally dissimilar donors for 19 GIs in the V. vulnificus CMCP6 genome, including chromosome I donating to chromosome II. This suggests multiple transfer events from individual donor types or from donors with similar genome signatures. Applied to other prokaryotes, this approach may elucidate the acquisition account in their genome sequences, and facilitate donor identification of GIs.

Algorithms↗