Phylogenomics with incomplete taxon coverage: the limits to inference

<p>Abstract</p> <p>Background</p> <p>Phylogenomic studies based on multi-locus sequence data sets are usually characterized by partial taxon coverage, in which sequences for some loci are missing for some taxa. The impact of missing data has been widely studied in phylogenetics, but it has proven difficult to distinguish effects due to error in tree reconstruction from effects due to missing data per se. We approach this problem using a explicitly phylogenomic criterion of success, <it>decisiveness</it>, which refers to whether the pattern of taxon coverage allows for uniquely defining a single tree for all taxa.</p> <p>Results</p> <p>We establish theoretical bounds on the impact of missing data on decisiveness. Results are derived for two contexts: a fixed taxon coverage pattern, such as that observed from an already assembled data set, and a randomly generated pattern derived from a process of sampling new data, such as might be observed in an ongoing comparative genomics sequencing project. Lower bounds on how many loci are needed for decisiveness are derived for the former case, and both lower and upper bounds for the latter. When data are not decisive for all trees, we estimate the probability of decisiveness and the chances that a given edge in the tree will be distinguishable. Theoretical results are illustrated using several empirical examples constructed by mining sequence databases, genomic libraries such as ESTs and BACs, and complete genome sequences.</p> <p>Conclusion</p> <p>Partial taxon coverage among loci can limit phylogenomic inference by making it impossible to distinguish among multiple alternative trees. However, even though lack of decisiveness is typical of many sparse phylogenomic data sets, it is often still possible to distinguish a large fraction of edges in the tree.</p

Back to the future: A back and forth manufacturing process journey from monoclonal antibodies to viral vectors for cell and gene therapy

The advent of new gene and cell therapies brings high promises to meet unmet medical needs. But, this also raises questions about how to produce these therapies cost effectively at scale. More specifically, producing enough high quality viral vector is key. Many early production and purification processes relied on techniques that are challenging to scale up, or are not commercially available at larger scales and sometimes even not compliant with cGMP. Scalable production and purification techniques from process development to cGMP compliant commercial manufacturing are therefore required. This feels like travelling back in time when the same challenges arose for the development of monoclonal antibodies. So instead of re-inventing the wheel, can we leverage lessons learnt from this past experience? Considering that processes for both mAbs and viral vectors include similar steps in term of cell culture, harvest, purification and formulation, the technologies developed and optimized for mAb manufacturing should therefore be applicable to viral vector processes. Here we will discuss the process similarities and differences for mAbs on one hand and adeno-associated viruses and lentiviruses on the other hand, focusing on gaps identified in developing process platforms for the production and purification of viral vectors. We will show how even the most recent advances in continuous bioprocessing for mAbs can be implemented quickly for viral vectors and the subsequent benefits generated in term of process productivity and economics

IPC2008-64685 A NOVEL TWO-PHASE GAS\LIQUID SLUG FLOW MEASUREMENT SYSTEM USING A T-JUNCTION SEPARATOR AND ULTRASONIC MEASUREMENTS

ABSTRACT Over the last decade, the development and deployment of in-line multiphase flow metering systems has been a major focus worldwide. Accurate measurement of multiphase flow in the oil and gas industry is difficult because it occurs in wide range of flow regimes and multiphase meters do not generally perform well under the intermittent slug flow conditions which commonly occur in oil production. A novel ultrasonic multiphase metering concept has been proposed and investigated which measures the flow rates of the liquid and gas phases from ultrasonic measurements made in two different flow regimes -partially separated and homogeneous -in the same measurement system and fuses the data from the different flow regimes to obtain improved overall measurement accuracy. The system employs a partial gas/liquid separation using a T-junction configuration and a combination of Doppler and cross correlation. The partially separated flow regimes uses ultrasonic cross correlation measurement for the liquid flow measurement which has gas entrained within it. The homogeneous regime employs ultrasonic Doppler method. This approach has been tested on water/air flows on a 50mm facility in the Department of Process and Systems Engineering. The liquid and gas flowrate measurements using the proposed techniques were compared with a reference measurement and good agreements between these two measurements were obtained with error ranging from ± 2 % and 10%, respectively. Such a performance offers the potential for an in-line multiphase flowmeter with improved performance