BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:CRUK computational biology day - Speaker to be confirmed DTSTART:20110418T080000Z DTEND:20110418T160000Z UID:TALK29820@talks.cam.ac.uk CONTACT:Florian Markowetz DESCRIPTION:With the continual growth of high throughput methods and techn ologies in biological science\, there is an increasing need for computatio nal and statistical analysis. As a result the number of bioinformaticians in CRUK is growing and will continue to grow for some time. This meeting will help to strengthen the ties between computational groups at different CRUK institutes by offering a forum to exchange ideas and skills.\n\nWe h ope to see lively discussions during the meeting (and thus allocated enoug h time between sessions) and encourage all participants to present a poste r of their research.\n\n%{color:red}*Registration Page*% ("click here":htt ps://survey.cancerresearchuk.org/Survey.aspx?s=5c4b306580c74426a4d3d113c21 44dcb)\n\n==========\n\n*PROGRAM*\n\n09:00-09:30 Welcome coffee \n\n*09:3 0-10:30 Session 1* \n* Andy Lynch [CRI] A note on a meddling mustelid\n* Y inyin Yuan [CRI] A sparse regulatory network of copy-number driven gene ex pression reveals putative breast cancer oncogenes\n\n10:30-11:00 break\n\n *11:00-12:00 Session 2*\n* Rory Stark [CRI]: Differential binding analysi s for ChIP-Seq: Occupancy vs. Affinity\n* Philip East [LRI]: Analysing a b lend of ChIP-Seq flavours to explain a GATA2 dependent cell death phenotyp e.\n\n \n12:00-13:00 lunch\n\n*13:00-14:00 Session 3*\n* Richard Mitter [ LRI]: Investigating TGF-β signalling. The trials and tribulations of an RNA-seq analysis project.\n* Katie Bentley [LRI]: Discovering mechanisms a nd dynamics in angiogenesis using an integrated simulation/experimentation approach\n\n14:00-14:30 break\n\n*14:30-15:30 Session 4*\n* Gabriela Kal na [Beatson] Matrix factorisation: microarrays and chemotaxis assays\n* Ro ger Phillips [Bradford] Impact of the tumour microenvironment on the deliv ery of drugs to tumours\n\n*15:30-17:00 POSTER session*\n\n17:00 END\n\n\n ==========\n\n*ABSTRACTS*\n\n*A note on a meddling mustelid*\n\n_Andy Lync h [CRI]_\n\nAs the size and complexity of a genomic study increases\, the probability that there will be sample-plating or sample-tracking errors in a study also increases. If you are in the business of analysing large and complex studies\, then this can then be a problem. I present an overview of the 'BADGER' method that we have developed to try and identify such err ors in a particularly complex study\, and discuss the implications of such an approach for other aspects of study design and analysis.\n\n\n*A spars e regulatory network of copy-number driven gene expression reveals putativ e breast cancer oncogenes*\n\n_Yinyin Yuan [CRI]_\n\nCopy number aberratio ns are recognized to be important in cancer as they may localize to region s\nharboring oncogenes or tumour suppressors. Such genomic alterations med iate phenotypic changes\nthrough their impact on expression. Both cis- and trans- acting alterations are important since they may\nhelp to elucidate putative cancer genes. However\, amidst numerous passenger genes\, trans- effects are\nless well studied due to the computational difficulty in dete cting weak and sparse signals in the data\,\nand yet may influence multipl e genes on a global scale. We propose an integrative approach to learn a\n sparse interaction network of DNA copy-number regions with their downstrea m transcriptional targets\nin breast cancer. \n\n*Differential binding ana lysis for ChIP-Seq: Occupancy vs. Affinity* \n\n_Rory Stark [CRI]_\n\nNext -gen sequencing has enabled protein/DNA binding to be mapped at a genomic level via ChIP-Seq. While much of the effort in computational analysis in this area has been devoted to identifying enriched regions in individual s amples (peak finding)\, derivation of meaningful biological results requir es differential analysis of many samples representing different replicates \, conditions\, and/or transcription factors. Such analyses typically focu s on DNA sites where the presence or absence of a protein binding event ch anges. While these occupancy-based analyses can identify binding sites uni que to a group of samples (albeit lacking reliable confidence statistics)\ , they are less able to differentiate between sites with a positive occupa ncy status in both conditions\, but where the affinity (proportion of cell s in the sample that are bound at that site) exhibits significant changes. I present techniques (encapsulated in an R package) for identifying such binding sites using methods developed for RNA-Seq and demonstrate their ef ficacy in isolating sites differentially bound between groups of ChIP-Seq samples\, showing how sample groups can be cleanly separated using only bi nding sites that are occupied in both groups but whose affinities differ s ignificantly\, as measured by FDR after multiple testing correction.\n\n*A nalysing a blend of ChIP-Seq flavours to explain a GATA2 dependent cell de ath phenotype*\n\n_Philip East [LRI]_\n\nWithin Bioinformatics and Biostat istics at the LRI ChIP-Seq remains our largest NGS application. Here we hi ghlight our efforts in this area focusing on an analysis containing data f rom a number of ChIP\nexperiments. In lung cancer cell lines with KRAS or EGFR mutations GATA2 knockdown is fatal. To try and identify transcription al control mechanisms that explain this phenotype GATA2\, RNA PolII and 3 flavours\nof histone methylation were chipped. We have integrated these da ta in an attempt to identify transcriptional control effects correlated wi th this\nphenotype.\n\n*Investigating TGF-β signalling. The trials and t ribulations of an RNA-seq analysis project.*\n\n_Richard Mitter [LRI]_\n\n The TGF-β signaling pathway is involved in many cellular processes in bot h the adult organism and the developing embryo including cell growth\, cel l differentiation\, apoptosis and cellular homeostasis. The pathway is cl assically considered to be formed of two halves that operate through diffe rent ligand-receptor partnerships to activate TGF-ß target genes. The wo rkhorses of both halves of the pathway are the Smad transcription factors that form complexes to transduce the signal from the membrane into the nuc leus. RNA-seq was used to investigate the effects of TGF-ß on gene expre ssion in the presence and absence of certain Smad factors in the hope of i dentifying a new branch to the TGF-ß pathway.\n\n\n*Discovering mechanism s and dynamics in angiogenesis using an integrated simulation/experimentat ion approach*\n \n_Katie Bentley [LRI]_\n\nAngiogenesis (the growth of new blood vessels) is a complex\, dynamic process. Multiple processes such as cell migration\, cell fate selection and cell rearrangement occur concurr ently to produce a regularly patterned branching blood vessel structure. T o pull apart and understand the underlying mechanisms driving these intera cting processes we have developed a 3D agent-based computational model\; u sed in iteration back and forth with experimentation this has led to a con tinual refinement of the model\, deeper understanding of important compone nts at work in cell fate selection and indicates an entirely novel behavio ur may have been discovered in pathological conditions such as cancer.\n\n \n*Matrix factorisation: microarrays and chemotaxis assays*\n\n_Gabriela K alna [Beatson]_\n\nThe spectral biclustering (SbC) based on the singular v alue decomposition is a widely used matrix factorization technique for lar ge data sets from high throughput experiments. It provides powerful unsupe rvised approach to identification of the main patterns as well as experime ntal artefacts within the data. Moreover\, SbC vectors simultaneously rear range rows and columns of the data set into distinct checkerboard patterns . In microarray analysis\, coupled with pathway/gene ontology and survival /clinical data\, this can identify functionally related prognostic gene se ts for head and neck squamous cell carcinoma. In image analysis of chemota xis it reveals aspects of complex cell boundary movements.\n\n*Impact of t he tumour microenvironment on the delivery of drugs to tumours*\n\n_Roger Phillips [Bradford]_\n\nThe concentration of drug delivered to the tumour and the duration of time the drug remains in residence at the tumour site are two key factors that will determine tumour response to chemotherapy. W ithin tumours however\, a microenvironment is created by a chaotic vascula r supply and altered tumour stroma that significantly hinders the delivery of therapeutically effective drug concentrations. During this presentatio n\, the impact of the tumour microenvironment on drug delivery will be des cribed in the context of providing experimental pharmacological data for t he development of in silico models. \n\n\n LOCATION:Cancer Research UK Cambridge Research Institute\, Lecture Theatre END:VEVENT END:VCALENDAR