Biomedical subjects

Maciej Swat

Publications and source records attributed to Maciej Swat.

5 recordsLinked to original sources

PubMed2005

HuSiDa--the human siRNA database: an open-access database for published functional siRNA sequences and technical details of efficient transfer into recipient cells.

Small interfering RNAs (siRNAs) have become a standard tool in functional genomics. Once incorporated into the RNA-induced silencing complex (RISC), siRNAs mediate the specific recognition of corresponding target mRNAs and their cleavage. However, only a small fraction of randomly chosen siRNA sequences is able to induce efficient gene silencing. In common laboratory practice, successful RNA interference experiments typically require both, the labour and cost-intensive identification of an active siRNA sequence and the optimization of target cell line-specific procedures for optimal siRNA delivery. To optimize the design and performance of siRNA experiments, we have established the human siRNA database (HuSiDa). The database provides sequences of published functional siRNA molecules targeting human genes and important technical details of the corresponding gene silencing experiments, including the mode of siRNA generation, recipient cell lines, transfection reagents and procedures and direct links to published references (PubMed). The database can be accessed at http://www.human-siRNA-database.net. We used the siRNA sequence information stored in the database for scrutinizing published sequence selection parameters for efficient gene silencing.

Base Sequence↗

PubMed2005

Biological profiling of gene groups utilizing Gene Ontology.

Increasingly used high throughput experimental techniques, like DNA or protein microarrays give as a result groups of interesting, e.g. differentially regulated genes which require further biological interpretation. With the systematic functional annotation provided by the Gene Ontology the information required to automate the interpretation task is now accessible. However, the determination of statistical significance of a biological process within these groups is still an open question. In answering this question, multiple testing issues must be taken into account to avoid misleading results. Here we present a statistical framework that tests whether functions, processes or locations described in the Gene Ontology are significantly enriched within a group of interesting genes when compared to a reference group. First we define an exact analytical expression for the expected number of false positives that allows us to calculate adjusted p-values to control the false discovery rate. Next, we demonstrate and discuss the capabilities of our approach using publicly available microarray data on cell-cycle regulated genes. Further, we analyze the robustness of our framework with respect to the exact gene group composition and compare the performance with earlier approaches. The software package GOSSIP implements our method and is made freely available at http://gossip.gene-groups.net/.

Binding Sites↗

PubMed2004

Bifurcation analysis of the regulatory modules of the mammalian G1/S transition.

MOTIVATION: Mathematical models of the cell cycle can contribute to an understanding of its basic mechanisms. Modern simulation tools make the analysis of key components and their interactions very effective. This paper focuses on the role of small modules and feedbacks in the gene-protein network governing the G1/S transition in mammalian cells. Mutations in this network may lead to uncontrolled cell proliferation. Bifurcation analysis helps to identify the key components of this extremely complex interaction network. RESULTS: We identify various positive and negative feedback loops in the network controlling the G1/S transition. It is shown that the positive feedback regulation of E2F1 and a double activator-inhibitor module can lead to bistability. Extensions of the core module preserve the essential features such as bistability. The complete model exhibits a transcritical bifurcation in addition to bistability. We relate these bifurcations to the cell cycle checkpoint and the G1/S phase transition point. Thus, core modules can explain major features of the complex G1/S network and have a robust decision taking function.

Animals↗

PubMed2003

etapi and eta'pi spectra and interpretation of possible exotic JPC=1-+ mesons.

We discuss a coupled channel analysis of the etapi and eta'pi systems produced in pi(-)p interactions at 18 GeV/c. We show that known Q(-)Q resonances, together with residual soft meson-meson rescattering, saturate the spectra including the exotic J(PC)=1(-+) channel. The possibility of a narrow exotic resonance at a mass near 1.6 GeV/c(2) cannot, however, be ruled out.

Journal Article↗

PubMed2003

Cytoskeletal remodeling in lymphocyte activation.

The formerly distinct fields of lymphocyte signal transduction and cytoskeletal remodeling have recently become linked, as proteins involved in transducing signals downstream of lymphocyte antigen receptors have also been implicated in actin cytoskeleton remodeling, microtubule dynamics and regulation of cell polarity. These discoveries have fuelled interest in understanding both the role of the actin cytoskeleton as an integral component of lymphocyte activation and the interplay between lymphoid cell-cell contact sites (immunological synapse), retractile pole structures (uropod, distal pole complex), and Rho-family GTPases (Rac, Rho, Cdc42), their upstream activators (Dbl-family guanine nucleotide exchange factors) and their downstream effectors (WASp, Arp2/3, ADAP). To understand how these complex regulatory networks are wired, a new breed of computational biologists uses mathematical language to reproduce and simulate signaling circuits 'in silico'.

Actin Cytoskeleton↗