A combined approach to data mining of textual and structured data to identify cancer-related targets

Background  

We present an effective, rapid, systematic data mining approach for identifying genes or proteins related to a particular interest. A selected combination of programs exploring PubMed abstracts, universal gene/protein databases (UniProt, InterPro, NCBI Entrez), and state-of-the-art pathway knowledge bases (LSGraph and Ingenuity Pathway Analysis) was assembled to distinguish enzymes with hydrolytic activities that are expressed in the extracellular space of cancer cells. Proteins were identified with respect to six types of cancer occurring in the prostate, breast, lung, colon, ovary, and pancreas.     

Motor control: from joints to objects and back

A new study shows that the nervous system has the flexibility to learn dynamics in object-centered coordinates - up to a limit.     

Estimating distribution of hidden objects with drones: from tennis balls to manatees

Unmanned aerial vehicles (UAV), or drones, have been used widely in military applications, but more recently civilian applications have emerged (e.g., wildlife population monitoring, traffic monitoring, law enforcement, oil and gas pipeline threat detection). UAV can have several advantages over manned aircraft for wildlife surveys, including reduced ecological footprint, increased safety, and the ability to collect high-resolution geo-referenced imagery that can document the presence of species without the use of a human observer. We illustrate how geo-referenced data collected with UAV technology in combination with recently developed statistical models can improve our ability to estimate the distribution of organisms. To demonstrate the efficacy of this methodology, we conducted an experiment in which tennis balls were used as surrogates of organisms to be surveyed. We used a UAV to collect images of an experimental field with a known number of tennis balls, each of which had a certain probability of being hidden. We then applied spatially explicit occupancy models to estimate the number of balls and created precise distribution maps. We conducted three consecutive surveys over the experimental field and estimated the total number of balls to be 328 (95%CI: 312, 348). The true number was 329 balls, but simple counts based on the UAV pictures would have led to a total maximum count of 284. The distribution of the balls in the field followed a simulated environmental gradient. We also were able to accurately estimate the relationship between the gradient and the distribution of balls. Our experiment demonstrates how this technology can be used to create precise distribution maps in which discrete regions of the study area are assigned a probability of presence of an object. Finally, we discuss the applicability and relevance of this experimental study to the case study of Florida manatee distribution at power plants.     

Projecting sensations to external objects: evidence from skin conductance response

Subjects perceived touch sensations as arising from a table (or a rubber hand) when both the table (or the rubber hand) and their own real hand were repeatedly tapped and stroked in synchrony with the real hand hidden from view. If the table or rubber hand was then 'injured', subjects displayed a strong skin conductance response (SCR) even though nothing was done to the real hand. Sensations could even be projected to anatomically impossible locations. The illusion was much less vivid, as indicated by subjective reports and SCR, if the real hand was simultaneously visible during stroking, or if the real hand was hidden but touched asynchronously. The fact that the illusion could be significantly diminished when the real hand was simultaneously visible suggests that the illusion and associated SCRs were due to perceptual assimilation of the table (or rubber hand) into one's body image rather than associative conditioning. These experiments demonstrate the malleability of body image and the brain's remarkable capacity for detecting statistical correlations in the sensory input.     

Separating spatially distributed response to stimulation from background. I. Optical imaging

We consider the problem of estimating a small stimulus-induced response to stimulation that is masked by a fluctuating background when measurements of the background in the absence of stimulation are available, as is common in optical imaging of the cortex and in many other experimental situations. Two related methods based on the Karhunen-Loève procedure are discussed. One seeks the function, an indicator function, that is most parallel to the response data and most orthogonal to the background data. The second removes the subspace spanned by the background from the response. Numerical investigations on simulated optical imaging data show that the first method is generally superior. Connections between the two methods and techniques for assessing the quality of the result are discussed. Received: 17 January 1997 / Accepted in revised form: 4 August 1997     

MADGE: scalable distributed data management software for cDNA microarrays

MOTIVATION: The human genome project and the development of new high-throughput technologies have created unparalleled opportunities to study the mechanism of diseases, monitor the disease progression and evaluate effective therapies. Gene expression profiling is a critical tool to accomplish these goals. The use of nucleic acid microarrays to assess the gene expression of thousands of genes simultaneously has seen phenomenal growth over the past five years. Although commercial sources of microarrays exist, investigators wanting more flexibility in the genes represented on the array will turn to in-house production. The creation and use of cDNA microarrays is a complicated process that generates an enormous amount of information. Effective data management of this information is essential to efficiently access, analyze, troubleshoot and evaluate the microarray experiments. RESULTS: We have developed a distributable software package designed to track and store the various pieces of data generated by a cDNA microarray facility. This includes the clone collection storage data, annotation data, workflow queues, microarray data, data repositories, sample submission information, and project/investigator information. This application was designed using a 3-tier client server model. The data access layer (1st tier) contains the relational database system tuned to support a large number of transactions. The data services layer (2nd tier) is a distributed COM server with full database transaction support. The application layer (3rd tier) is an internet based user interface that contains both client and server side code for dynamic interactions with the user. AVAILABILITY: This software is freely available to academic institutions and non-profit organizations at http://www.genomics.mcg.edu/niddkbtc.     

MedEvi: retrieving textual evidence of relations between biomedical concepts from Medline

Search engines running on MEDLINE abstracts have been widely used by biologists to find publications that are related to their research. The existing search engines such as PubMed, however, have limitations when applied for the task of seeking textual evidence of relations between given concepts. The limitations are mainly due to the problem that the search engines do not effectively deal with multi-term queries which may imply semantic relations between the terms. To address this problem, we present MedEvi, a novel search engine that imposes positional restriction on occurrences matching multi-term queries, based on the observation that terms with semantic relations which are explicitly stated in text are not found too far from each other. MedEvi further identifies additional keywords of biological and statistical significance from local context of matching occurrences in order to help users reformulate their queries for better results. AVAILABILITY: http://www.ebi.ac.uk/tc-test/textmining/medevi/     

Things to think with: words and objects as material symbols

This paper integrates archaeology, anthropology and functional brain imaging in an examination of the cognition of words and objects. Based on a review of recent brain imaging experiments, it is argued that in cognition and action, material symbols may be the link between internal representations and objects and words in the world. This principle is applied to the sapient paradox, the slow development of material innovation at the advent of the anatomically modern human. This translates the paradox into a long-term build-up of extended and distributed cognition supported by development in the complexity of material symbols.     

Sample size calculations for noninferiority trials with Poisson distributed count data

Clinical trials with Poisson distributed count data as the primary outcome are common in various medical areas such as relapse counts in multiple sclerosis trials or the number of attacks in trials for the treatment of migraine. In this article, we present approximate sample size formulae for testing noninferiority using asymptotic tests which are based on restricted or unrestricted maximum likelihood estimators of the Poisson rates. The Poisson outcomes are allowed to be observed for unequal follow‐up schemes, and both the situations that the noninferiority margin is expressed in terms of the difference and the ratio are considered. The exact type I error rates and powers of these tests are evaluated and the accuracy of the approximate sample size formulae is examined. The test statistic using the restricted maximum likelihood estimators (for the difference test problem) and the test statistic that is based on the logarithmic transformation and employs the maximum likelihood estimators (for the ratio test problem) show favorable type I error control and can be recommended for practical application. The approximate sample size formulae show high accuracy even for small sample sizes and provide power values identical or close to the aspired ones. The methods are illustrated by a clinical trial example from anesthesia.     

Peach: a simple Perl-based system for distributed computation and its application to cryo-EM data processing

A simple distributed processing system named "Peach" was developed to meet the rising computational demands of modern structural biology (and other) laboratories without additional expense by using existing hardware resources more efficiently. A central server distributes jobs to idle workstations in such a way that each computer is used maximally, but without disturbing intermittent interactive users. As compared to other distributed systems, Peach is simple, easy to install, easy to administer, easy to use, scalable, and robust. While it was designed to queue and distribute large numbers of small tasks to participating computers, it can also be used to send single jobs automatically to the fastest currently available computer and/or survey the activity of an entire laboratory's computers. Tests of robustness and scalability are reported, as are three specific electron cryomicroscopy applications where Peach enabled projects that would not otherwise have been feasible without an expensive, dedicated cluster.     

A life scientist's gateway to distributed data management and computing: the PathPort/ToolBus framework

The emergent needs of the bioinformatics community challenge current information systems. The pace of biological data generation far outstrips Moore's Law. Therefore, a gap continues to widen between the capabilities to produce biological (molecular and cell) data sets and the capability to manage and analyze these data sets. As a result, Federal investments in large data set generation produces diminishing returns in terms of the community's capabilities of understanding biology and leveraging that understanding to make scientific and technological advances that improve society. We are building an open framework to address various data management issues including data and tool interoperability, nomenclature and data communication standardization, and database integration. PathPort, short for Pathogen Portal, employs a generic, web-services based framework to deal with some of the problems identified by the bioinformatics community. The motivating research goal of a scalable system to provide data management and analysis for key pathosystems, especially relating to molecular data, has resulted in a generic framework using two major components. On the server-side, we employ web-services. On the client-side, a Java application called ToolBus acts as a client-side "bus" for contacting data and tools and viewing results through a single, consistent user interface.     

Bacillus endospores isolated from granite: close molecular relationships to globally distributed Bacillus spp. from endolithic and extreme environments

As part of an ongoing effort to catalog spore-forming bacterial populations in environments conducive to interplanetary transfer by natural impacts or by human spaceflight activities, spores of Bacillus spp. were isolated and characterized from the interior of near-subsurface granite rock collected from the Santa Catalina Mountains, AZ. Granite was found to contain approximately 500 cultivable Bacillus spores and approximately 10(4) total cultivable bacteria per gram. Many of the Bacillus isolates produced a previously unreported diffusible blue fluorescent compound. Two strains of eight tested exhibited increased spore UV resistance relative to a standard Bacillus subtilis UV biodosimetry strain. Fifty-six isolates were identified by repetitive extragenic palindromic PCR (rep-PCR) and 16S rRNA gene analysis as most closely related to B. megaterium (15 isolates), B. simplex (23 isolates), B. drentensis (6 isolates), B. niacini (7 isolates), and, likely, a new species related to B. barbaricus (5 isolates). Granite isolates were very closely related to a limited number of Bacillus spp. previously found to inhabit (i) globally distributed endolithic sites such as biodeteriorated murals, stone tombs, underground caverns, and rock concretions and (ii) extreme environments such as Antarctic soils, deep sea floor sediments, and spacecraft assembly facilities. Thus, it appears that the occurrence of Bacillus spp. in endolithic or extreme environments is not accidental but that these environments create unique niches excluding most Bacillus spp. but to which a limited number of Bacillus spp. are specifically adapted.     

Crocodilian evolution: insights from immunological data.

The quantitative immunological technique of microcomplement fixation was used to examine serum albumin evolution among members of the order Crocodylia. The cross-reactivity of the albumin antisera and antigens employed in this study had been examined previously using the qualitative technique of immunodiffusion. The phylogenetic conclusions derived from these two data sets are highly congruent, including support of the families Alligatoridae and Crocodylidae, with the placement of Gavialis as the sister taxon of Tomistoma. Both methods provide similar information on the relative amounts of amino acid sequence divergence between albumin molecules; however, the data obtained from microcomplement fixation comparisons are more discriminating than those derived from immunodiffusion. The estimated divergence times within the Crocodylia derived from the fossil record are examined in light of divergence times predicted by the microcomplement fixation-based albumin clock. The traditional phylogenetic placement of Gavialis outside the remaining extant crocodilians is inconsistent with all molecular data sets and we suggest that a careful reexamination of both the extant and the fossil morphological data is warranted.     

Bioinformatics: from genome data to biological knowledge

Recently, molecular biologists have sequenced about a dozen bacterial genomes and the first eukaryotic genome. We can now obtain answers to detailed questions about the complete set of genes of an organism. Bioinformatics methods are increasingly used for attaching biological knowledge to long lists of genes, assigning genes to biological pathways, comparing the gene sets of different species, identifying specificity factors, and describing sets of highly conserved proteins common to all domains of life. Substantial progress has recently been made in the availability of primary and added-value databases, in the development of algorithms and of network information services for genome analysis. The pharmaceutical industry has greatly benefited from the accumulation of sequence data through the identification of targets and candidates for the development of drugs, vaccines, diagnostic markers and therapeutic proteins.