Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy

Background. Cardiac allograft vasculopathy (CAV) is a major cause of graft loss and death after heart transplantation. Currently, no diagnostic methods are available during the early post-transplant period to accurately identify patients at risk of CAV. We hypothesized that PBMC gene expression profiles (GEP) can identify patients at risk of CAV. Methods. We retrospectively analyzed a limited set of whole-genome PBMC microarrays from 10 post-transplant patients who did (n = 3) or did not (n = 7) develop advanced grade CAV during their long-term follow-up. We used significance analysis of microarrays to identify differentially expressed genes and High-Throughput GoMiner to assess gene ontology (GO) categories. We corroborated our findings by retrospective analysis of PBMC real-time PCR data from 33 patients. Results. Over 300 genes were differentially expressed (FDR < 5%), and 18 GO-categories including “macrophage activation”, “Interleukin-6 pathway”, “NF-KappaB cascade”, and “response to virus” were enriched by these genes (FDR < 5%). Out of 8 transcripts available for RT-PCR analysis, we confirmed 6 transcripts (75.0%) including FPRL1, S100A9, CXCL10, PRO1073, and MMP9 (P < .05). Conclusion. Our pilot data suggest that GEP of PBMC may become a valuable tool in the evaluation of patients at risk of CAV. Larger prospectively designed studies are needed to corroborate our hypothesis

A Platform for Processing Expression of Short Time Series (PESTS)

<p>Abstract</p> <p>Background</p> <p>Time course microarray profiles examine the expression of genes over a time domain. They are necessary in order to determine the complete set of genes that are dynamically expressed under given conditions, and to determine the interaction between these genes. Because of cost and resource issues, most time series datasets contain less than 9 points and there are few tools available geared towards the analysis of this type of data.</p> <p>Results</p> <p>To this end, we introduce a platform for Processing Expression of Short Time Series (PESTS). It was designed with a focus on usability and interpretability of analyses for the researcher. As such, it implements several standard techniques for comparability as well as visualization functions. However, it is designed specifically for the unique methods we have developed for significance analysis, multiple test correction and clustering of short time series data. The central tenet of these methods is the use of biologically relevant features for analysis. Features summarize short gene expression profiles, inherently incorporate dependence across time, and allow for both full description of the examined curve and missing data points.</p> <p>Conclusions</p> <p>PESTS is fully generalizable to other types of time series analyses. PESTS implements novel methods as well as several standard techniques for comparability and visualization functions. These features and functionality make PESTS a valuable resource for a researcher's toolkit. PESTS is available to download for free to academic and non-profit users at <url>http://www.mailman.columbia.edu/academic-departments/biostatistics/research-service/software-development</url>.</p

Time-series clustering of gene expression in irradiated and bystander fibroblasts: an application of FBPA clustering

<p>Abstract</p> <p>Background</p> <p>The radiation bystander effect is an important component of the overall biological response of tissues and organisms to ionizing radiation, but the signaling mechanisms between irradiated and non-irradiated bystander cells are not fully understood. In this study, we measured a time-series of gene expression after α-particle irradiation and applied the Feature Based Partitioning around medoids Algorithm (FBPA), a new clustering method suitable for sparse time series, to identify signaling modules that act in concert in the response to direct irradiation and bystander signaling. We compared our results with those of an alternate clustering method, Short Time series Expression Miner (STEM).</p> <p>Results</p> <p>While computational evaluations of both clustering results were similar, FBPA provided more biological insight. After irradiation, gene clusters were enriched for signal transduction, cell cycle/cell death and inflammation/immunity processes; but only FBPA separated clusters by function. In bystanders, gene clusters were enriched for cell communication/motility, signal transduction and inflammation processes; but biological functions did not separate as clearly with either clustering method as they did in irradiated samples. Network analysis confirmed p53 and NF-κB transcription factor-regulated gene clusters in irradiated and bystander cells and suggested novel regulators, such as KDM5B/JARID1B (lysine (K)-specific demethylase 5B) and HDACs (histone deacetylases), which could epigenetically coordinate gene expression after irradiation.</p> <p>Conclusions</p> <p>In this study, we have shown that a new time series clustering method, FBPA, can provide new leads to the mechanisms regulating the dynamic cellular response to radiation. The findings implicate epigenetic control of gene expression in addition to transcription factor networks.</p

Improved recognition module for the interpretation of handwritten digits

Thesis (S.B. and M.Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1999.Includes bibliographical references (leaves 75-76).by Anshu Sinha.S.B.and M.Eng

Karakoram: An Integral Part of Perigondwana ProvinceFossiliferous Evidences

86-91The sedimentary sequence from the Chongtash Formation, Karakoram area (Upper Shyok Valley) has yielded Lower Gondwana palynomorphs referable to Early Permian age. Though these palynomorphs are not well preserved but can be identified at generic level. The palynoassemblage shows dominance of monosaccates viz. Parasaccites, Plicatipollenites, Divarisaccus, and Caheniasaccites. Few striate disaccates viz. Striatopodocarpites, Faunipollenites, Striatites and non-striate disaccates viz. Scheuring ipollenites and Ibisporites have also been recorded. Among trlietes presence of Callumispora and <i style="mso-bidi-font-style: normal">Indotriradites have been observed. Except <i style="mso-bidi-font-style: normal">Cordaitina all taxa undoubtedly belong to Gondwana. The palynocomposition especially dominance of Parasaccites and presence of few striate and non-striate disaccates shows that the assemblage is equivalent to Talchir/ Upper Karharbari Formation (Late Asselian-Sakmarian) of India. This palynoassemblage from Chongtash Formation of Karakoram also shows resemblance with marine Lower Gondwana palynoassemblage of Salt Range (Pakistan). This finding of early Permian palynomorphs from Chongtash Formation of Karakoram area also supports the contention that during early Permian Karakoram was a part of Peri-Gondwanan province and was located on the northern margin of Indian subcontinent