Strategic management of population programs

Formal strategic planning and management appear to contribute to organizational effectiveness. The author surveys the literature on strategic management in private/for-profit organizations and applies lessons from that literature to population programs. Few would argue that population programs would not benefit from strategic planning and management, but it would be inadvisable to initiate the process when the organization is faced with a short-term crisis; during or immediately before a change in leadership; or when implementation is unlikely. Public sector programs seem to have the latitude to manage strategically. Models available for adoption include life-cycle models, strategic issues management, stakeholder analysis, and portfolio analysis. The model selected may be a function of: (1) who will use it (life-cycle/evolutionary models may be well-suited to the planning needs of donors); (2) the presence of challenges to the survival of the program or to key components of it (stakeholder analysis would find ready application in those circumstances); and (3) the relative success and stability of the program (portfolio analysis may help a program balance its activities in a stable environment whereas strategic issues management is useful in responding to a dynamic environment.) It is important to marshall top-level support, designatewho will do the leg work, analyze the organization's history and current situation, assess internal strengths and weaknesses and external threats and opportunities, and summarize critical issues facing the program. Then a strategy may be developed. Among the available approaches are: (1) scenario developments (useful for a program that senses a need to change its approach to clients); (2) critical issues analysis (useful for refining successful programs); and (3) a goal approach (useful for programs with diffuse, ill-defined objectives). There are no short-cuts, it is argued. A strategic plan typically contains: (1) a mission statement that describes the social need to be addressed, what is unique about the organization, what its values are, and who the principal stakeholders are; (2) a statement of the population to be served and goals for service delivery and quality standards; (3) a service delivery strategy; (4) a financial strategy; (5) a marketing strategy; and (6) support strategies. Most organizations will find that there is no ideal structure - all require tradeoffs - and that attention should focus on eliminating patently dysfunctional aspects of the structure.Health Monitoring&Evaluation,ICT Policy and Strategies,Agricultural Knowledge&Information Systems,Educational Sciences,Enterprise Development&Reform

Alignment of RNA base pairing probability matrices

Motivation: Many classes of functional RNA molecules are characterized by highly conserved secondary structures but little detectable sequence similarity. Reliable multiple alignments can therefore be constructed only when the shared structural features are taken into account. Since multiple alignments are used as input for many subsequent methods of data analysis, structure-based alignments are an indispensable necessity in RNA bioinformatics. Results: We present here a method to compute pairwise and progressive multiple alignments from the direct comparison of base pairing probability matrices. Instead of attempting to solve the folding and the alignment problem simultaneously as in the classical Sankoff's algorithm, we use McCaskill's approach to compute base pairing probability matrices which effectively incorporate the information on the energetics of each sequences. A novel, simplified variant of Sankoff's algorithms can then be employed to extract the maximum-weight common secondary structure and an associated alignment

Strategies for measuring evolutionary conservation of RNA secondary structures

<p>Abstract</p> <p>Background</p> <p>Evolutionary conservation of RNA secondary structure is a typical feature of many functional non-coding RNAs. Since almost all of the available methods used for prediction and annotation of non-coding RNA genes rely on this evolutionary signature, accurate measures for structural conservation are essential.</p> <p>Results</p> <p>We systematically assessed the ability of various measures to detect conserved RNA structures in multiple sequence alignments. We tested three existing and eight novel strategies that are based on metrics of folding energies, metrics of single optimal structure predictions, and metrics of structure ensembles. We find that the folding energy based SCI score used in the RNAz program and a simple base-pair distance metric are by far the most accurate. The use of more complex metrics like for example tree editing does not improve performance. A variant of the SCI performed particularly well on highly conserved alignments and is thus a viable alternative when only little evolutionary information is available. Surprisingly, ensemble based methods that, in principle, could benefit from the additional information contained in sub-optimal structures, perform particularly poorly. As a general trend, we observed that methods that include a consensus structure prediction outperformed equivalent methods that only consider pairwise comparisons.</p> <p>Conclusion</p> <p>Structural conservation can be measured accurately with relatively simple and intuitive metrics. They have the potential to form the basis of future RNA gene finders, that face new challenges like finding lineage specific structures or detecting mis-aligned sequences.</p

The Vienna RNA Websuite

The Vienna RNA Websuite is a comprehensive collection of tools for folding, design and analysis of RNA sequences. It provides a web interface to the most commonly used programs of the Vienna RNA package. Among them, we find folding of single and aligned sequences, prediction of RNA–RNA interactions, and design of sequences with a given structure. Additionally, we provide analysis of folding landscapes using the barriers program and structural RNA alignments using LocARNA. The web server together with software packages for download is freely accessible at http://rna.tbi.univie.ac.at/

Optimal strategies for a game on amenable semigroups

The semigroup game is a two-person zero-sum game defined on a semigroup S as follows: Players 1 and 2 choose elements x and y in S, respectively, and player 1 receives a payoff f(xy) defined by a function f from S to [-1,1]. If the semigroup is amenable in the sense of Day and von Neumann, one can extend the set of classical strategies, namely countably additive probability measures on S, to include some finitely additive measures in a natural way. This extended game has a value and the players have optimal strategies. This theorem extends previous results for the multiplication game on a compact group or on the positive integers with a specific payoff. We also prove that the procedure of extending the set of allowed strategies preserves classical solutions: if a semigroup game has a classical solution, this solution solves also the extended game.Comment: 17 pages. To appear in International Journal of Game Theor

The Evolving Faces of the SARS-CoV-2 Genome

Surveillance of the evolving SARS-CoV-2 genome combined with epidemiological monitoring and emerging vaccination became paramount tasks to control the pandemic which is rapidly changing in time and space. Genomic surveillance must combine generation and sharing sequence data with appropriate bioinformatics monitoring and analysis methods. We applied molecular portrayal using self-organizing maps machine learning (SOM portrayal) to characterize the diversity of the virus genomes, their mutual relatedness and development since the beginning of the pandemic. The genetic landscape obtained visualizes the relevant mutations in a lineage-specific fashion and provides developmental paths in genetic state space from early lineages towards the variants of concern alpha, beta, gamma and delta. The different genes of the virus have specific footprints in the landscape reflecting their biological impact. SOM portrayal provides a novel option for ‘bioinformatics surveillance’ of the pandemic, with strong odds regarding visualization, intuitive perception and ‘personalization’ of the mutational patterns of the virus genomes

Translational Control by RNA-RNA Interaction: Improved Computation of RNA-RNA Binding Thermodynamics

The thermodynamics of RNA-RNA interaction consists of two components: the energy necessary to make a potential binding region accessible, i.e., unpaired, and the energy gained from the base pairing of the two interaction partners. We show here that both components can be efficiently computed using an improved variant of RNAup. The method is then applied to a set of bacterial small RNAs involved in translational control. In all cases of biologically active sRNA target interactions, the target sites predicted by RNAup is in perfect agreement with literature. In addition to prediction of target site location, RNAup can be also be used to determine the mode of sRNA action. Using information about target site location and the accessibility change resulting form sRNA binding we can discriminate between positive and negative regulators of translation

Changes of bivalent chromatin coincide with increased expression of developmental genes in cancer

Bivalent (poised or paused) chromatin comprises activating and repressing histone modifications at the same location. This combination of epigenetic marks at promoter or enhancer regions keeps genes expressed at low levels but poised for rapid activation. Typically, DNA at bivalent promoters is only lowly methylated in normal cells, but frequently shows elevated methylation levels in cancer samples. Here, we developed a universal classifier built from chromatin data that can identify cancer samples solely from hypermethylation of bivalent chromatin. Tested on over 7,000 DNA methylation data sets from several cancer types, it reaches an AUC of 0.92. Although higher levels of DNA methylation are often associated with transcriptional silencing, counter-intuitive positive statistical dependencies between DNA methylation and expression levels have been recently reported for two cancer types. Here, we re-analyze combined expression and DNA methylation data sets, comprising over 5,000 samples, and demonstrate that the conjunction of hypermethylation of bivalent chromatin and up-regulation of the corresponding genes is a general phenomenon in cancer. This up-regulation affects many developmental genes and transcription factors, including dozens of homeobox genes and other genes implicated in cancer. Thus, we reason that the disturbance of bivalent chromatin may be intimately linked to tumorigenesis

Thermodynamics of RNA-RNA binding

Background: Reliable prediction of RNA–RNA binding energies is crucial, e.g. for the understanding on RNAi, microRNA–mRNA binding and antisense interactions. The thermodynamics of such RNA–RNA interactions can be understood as the sum of two energy contributions: (1) the energy necessary to ‘open’ the binding site and (2) the energy gained from hybridization. Methods: We present an extension of the standard partition function approach to RNA secondary structures that computes the probabilities Pu[i, j] that a sequence interval [i, j] is unpaired. Results: Comparison with experimental data shows that Pu[i, j] can be applied as a significant determinant of local target site accessibility for RNA interference (RNAi). Furthermore, these quantities can be used to rigorously determine binding free energies of short oligomers to large mRNA targets. The resource consumption is comparable with a single partition function computation for the large target molecule. We can show that RNAi efficiency correlates well with the binding energies of siRNAs to their respective mRNA target