REEF: searching REgionally Enriched Features in genomes

BACKGROUND: In Eukaryotic genomes, different features including genes are not uniformly distributed. The integration of annotation information and genomic position of functional DNA elements in the Eukaryotic genomes opened the way to test novel hypotheses of higher order genome organization and regulation of expression. RESULTS: REEF is a new tool, aimed at identifying genomic regions enriched in specific features, such as a class or group of genes homogeneous for expression and/or functional characteristics. The method for the calculation of local feature enrichment uses test statistic based on the Hypergeometric Distribution applied genome-wide by using a sliding window approach and adopting the False Discovery Rate for controlling multiplicity. REEF software, source code and documentation are freely available at . CONCLUSION: REEF can aid to shed light on the role of organization of specific genomic regions in the determination of their functional role

Genomic landscape characterization of large granular lymphocyte leukemia with a systems genetics approach

Non peer reviewe

CircRNAs in hematopoiesis and hematological malignancies

Cell states in hematopoiesis are controlled by master regulators and by complex circuits of a growing family of RNA species impacting cell phenotype maintenance and plasticity. Circular RNAs (circRNAs) are rapidly gaining the status of particularly stable transcriptome members with distinctive qualities. RNA-seq identified thousands of circRNAs with developmental stage-A nd tissue-specific expression corroborating earlier suggestions that circular isoforms are a natural feature of the cell expression program. CircRNAs are abundantly expressed also in the hematopoietic compartment. There are a number of studies on circRNAs in blood cells, a specific overview is however lacking. In this review we first present current insight in circRNA biogenesis discussing the relevance for hematopoiesis of the highly interleaved processes of splicing and circRNA biogenesis. Regarding molecular functions circRNAs modulate host gene expression, but also compete for binding of microRNAs, RNA-binding proteins or translation initiation and participate in regulatory circuits. We examine circRNA expression in the hematopoietic compartment and in hematologic malignancies and review the recent breakthrough study that identified pathogenic circRNAs derived from leukemia fusion genes. CircRNA high and regulated expression in blood cell types indicate that further studies are warranted to inform the position of these regulators in normal and malignant hematopoiesis

Possibilities for Measurement and Compensation of Stray DC Electric Fields Acting on Drag-Free Test Masses

DC electric fields can combine with test mass charging and thermal dielectric voltage noise to create significant force noise acting on the drag-free test masses in the LISA (Laser Interferometer Space Antenna) gravitational wave mission. This paper proposes a simple technique to measure and compensate average stray DC potentials at the mV level, yielding substantial reduction in this source of force noise. We discuss the attainable resolution for both flight and ground based experiments.Comment: To be published in Advances in Space Research, COSPAR 2002 conference proceedings (6 pages, 3 figures

Measuring random force noise for LISA aboard the LISA Pathfinder mission

The LTP (LISA Testflight Package), to be flown aboard the ESA / NASA LISA Pathfinder mission, aims to demonstrate drag-free control for LISA test masses with acceleration noise below 30 fm/s^2/Hz^1/2 from 1-30 mHz. This paper describes the LTP measurement of random, position independent forces acting on the test masses. In addition to putting an overall upper limit for all source of random force noise, LTP will measure the conversion of several key disturbances into acceleration noise and thus allow a more detailed characterization of the drag-free performance to be expected for LISA.Comment: 7 pages, 3 figures. To be published in Classical and Quantum Gravity with the proceedings of the 2003 Amaldi Meetin

Impact of probe annotation on the integration of miRNA-mRNA expression profiles for miRNA target detection

MicroRNAs (miRNAs) are small non-coding RNAs that mediate gene expression at the post-transcriptional and translational levels by an imperfect binding to target mRNA 3'UTR regions. While the ab-initio computational prediction of miRNA-mRNA interactions still poses significant challenges, it is possible to overcome some of its limitations by carefully integrating into the analysis the paired expression profiles of miRNAs and mRNAs. In this work, we show how the choice of a proper probe annotation for microarray platforms is an essential requirement to achieve good sensitivity in the identification of miRNA-mRNA interactions. We compare the results obtained from the analysis of the same expression profiles using both gene and transcript based custom CDFs that we have developed for a number of different annotations (ENSEMBL, RefSeq, AceView). In all cases, transcript-based annotations clearly improve the effectiveness of data integration and thus provide a more reliable confirmation of computationally predicted miRNA-mRNA interaction

Identification of differentially expressed small RNAs and prediction of target genes in Italian Large White pigs with divergent backfat deposition

The identification of the molecular mechanisms regulating pathways associated with the potential for fat deposition in pigs can lead to the detection of key genes and markers for the genetic improvement of fat traits. Interactions of microRNAs (miRNAs) with target RNAs regulate gene expression and modulate pathway activation in cells and tissues. In pigs, miRNA discovery is far from saturation, and the knowledge of miRNA expression in backfat tissue and particularly of the impact of miRNA variations is still fragmentary. Using RNA-seq, we characterized the small RNA (sRNA) expression profiles in Italian Large White pig backfat tissue. Comparing two groups of pigs divergent for backfat deposition, we detected 31 significant differentially expressed (DE) sRNAs: 14 up-regulated (including ssc-miR-132, ssc-miR-146b, ssc-miR-221-5p, ssc-miR-365-5p and the moRNA ssc-moR-21-5p) and 17 down-regulated (including ssc-miR-136, ssc-miR-195, ssc-miR-199a-5p and ssc-miR-335). To understand the biological impact of the observed miRNA expression variations, we used the expression correlation of DE miRNA target transcripts expressed in the same samples to define a regulatory network of 193 interactions between DE miRNAs and 40 DE target transcripts showing opposite expression profiles and being involved in specific pathways. Several miRNAs and mRNAs in the network were found to be expressed from backfat-related pig QTL. These results are informative for the complex mechanisms influencing fat traits, shed light on a new aspect of the genetic regulation of fat deposition in pigs and facilitate the prospective implementation of innovative strategies of pig genetic improvement based on genomic markers

Detecting seeded motifs in DNA sequences

The problem of detecting DNA motifs with functional relevance in real biological sequences is difficult due to a number of biological, statistical and computational issues and also because of the lack of knowledge about the structure of searched patterns. Many algorithms are implemented in fully automated processes, which are often based upon a guess of input parameters from the user at the very first step. In this paper, we present a novel method for the detection of seeded DNA motifs, composed by regions with a different extent of variability. The method is based on a multi-step approach, which was implemented in a motif searching web tool (MOST). Overrepresented exact patterns are extracted from input sequences and clustered to produce motifs core regions, which are then extended and scored to generate seeded motifs. The combination of automated pattern discovery algorithms and different display tools for the evaluation and selection of results at several analysis steps can potentially lead to much more meaningful results than complete automation can produce. Experimental results on different yeast and human real datasets proved the methodology to be a promising solution for finding seeded motifs. MOST web tool is freely available at

Measuring the LISA test mass magnetic proprieties with a torsion pendulum

Achieving the low frequency LISA sensitivity requires that the test masses acting as the interferometer end mirrors are free-falling with an unprecedented small degree of deviation. Magnetic disturbances, originating in the interaction of the test mass with the environmental magnetic field, can significantly deteriorate the LISA performance and can be parameterized through the test mass remnant dipole moment $\vec{m}_r$ and the magnetic susceptibility $\chi$. While the LISA test flight precursor LTP will investigate these effects during the preliminary phases of the mission, the very stringent requirements on the test mass magnetic cleanliness make ground-based characterization of its magnetic proprieties paramount. We propose a torsion pendulum technique to accurately measure on ground the magnetic proprieties of the LISA/LTP test masses.Comment: 6 pages, 3 figure

The early detection of osteoporosis in a cohort of healthcare workers: Is there room for a screening program?

Workforce aging is becoming a significant public health problem due to the resulting emergence of age-related diseases, such as osteoporosis. The prevention and early detection of osteoporosis is important to avoid bone fractures and their socio-economic burden. The aim of this study is to evaluate the sustainability of a screening workplace program able to detect workers with osteoporosis. The screening process included a questionnaire-based risk assessment of 1050 healthcare workers followed by measurement of the bone mass density (BMD) with a pulse-echo ultrasound (PEUS) at the proximal tibia in the at-risk subjects. Workers with a BMD value 64 0.783 g/cm\ub2 were referred to a specialist visit ensuring a diagnosis and the consequent prescriptions. Any possible association between the outcome variable BMD 64 0.783 g/cm\ub2 and the risk factors was eval-uated. The costs were calculated with a full costing method. We identified 60 pathological subjects. We observed increased risks for women, older ages, and menopause (p < 0.01). The yearly cost of our screening program estimated for this study was 8242 euros, and, considering the fragility bone fracture costs, we hypothesize a considerable economic savings, with a possible positive bene-fits/cost ratio of 2.07. We can say that the margin between the investment and results leads to a preference for this type of screening program. Osteoporosis is an occupational health problem, and a workplace screening program could be a cost-effective intervention