Hematopoietic gene promoters subjected to a group-combinatorial study of DNA samples: identification of a megakaryocytic selective DNA signature

Identification of common sub-sequences for a group of functionally related DNA sequences can shed light on the role of such elements in cell-specific gene expression. In the megakaryocytic lineage, no one single unique transcription factor was described as linage specific, raising the possibility that a cluster of gene promoter sequences presents a unique signature. Here, the megakaryocytic gene promoter group, which consists of both human and mouse 5' non-coding regions, served as a case study. A methodology for group-combinatorial search has been implemented as a customized software platform. It extracts the longest common sequences for a group of related DNA sequences and allows for single gaps of varying length, as well as double- and multiple-gap sequences. The results point to common DNA sequences in a group of genes that is selectively expressed in megakaryocytes, and which does not appear in a large group of control, random and specific sequences. This suggests a role for a combination of these sequences in cell-specific gene expression in the megakaryocytic lineage. The data also point to an intrinsic cross-species difference in the organization of 5' non-coding sequences within the mammalian genomes. This methodology may be used for the identification of regulatory sequences in other lineages.

How Good are Genetic Algorithms at Finding Large Cliques: An Experimental Study

This paper investigates the power of genetic algorithms at solving the MAX-CLIQUE problem. We measure the performance of a standard genetic algorithm on an elementary set of problem instances consisting of embedded cliques in random graphs. We indicate the need for improvement, and introduce a new genetic algorithm, the multi-phase annealed GA, which exhibits superior performance on the same problem set. As we scale up the problem size and test on \hard" benchmark instances, we notice a degraded performance in the algorithm caused by premature convergence to local minima. To alleviate this problem, a sequence of modi cations are implemented ranging from changes in input representation to systematic local search. The most recent version, called union GA, incorporates the features of union cross-over, greedy replacement, and diversity enhancement. It shows a marked speed-up in the number of iterations required to find a given solution, as well as some improvement in the clique size found. We discuss issues related to the SIMD implementation of the genetic algorithms on a Thinking Machines CM-5, which was necessitated by the intrinsically high time complexity (O(n3)) of the serial algorithm for computing one iteration. Our preliminary conclusions are: (1) a genetic algorithm needs to be heavily customized to work "well" for the clique problem; (2) a GA is computationally very expensive, and its use is only recommended if it is known to find larger cliques than other algorithms; (3) although our customization e ort is bringing forth continued improvements, there is no clear evidence, at this time, that a GA will have better success in circumventing local minima.

Program Representation Size in an Intermediate Language with Intersection and Union Types

The CIL compiler for core Standard ML compiles whole programs using a novel typed intermediate language (TIL) with intersection and union types and flow labels on both terms and types. The CIL term representation duplicates portions of the program where intersection types are introduced and union types are eliminated. This duplication makes it easier to represent type information and to introduce customized data representations. However, duplication incurs compile-time space costs that are potentially much greater than are incurred in TILs employing type-level abstraction or quantification. In this paper, we present empirical data on the compile-time space costs of using CIL as an intermediate language. The data shows that these costs can be made tractable by using sufficiently fine-grained flow analyses together with standard hash-consing techniques. The data also suggests that non-duplicating formulations of intersection (and union) types would not achieve significantly better space complexity.

Examples of Network Flow Verification Using TRAFFIC(X)

In our previous work, we developed TRAFFIC(X), a specification language for modeling bi-directional network flows featuring a type system with constrained polymorphism. In this paper, we present two ways to customize the constraint system: (1) when using linear inequality constraints for the constraint system, TRAFFIC(X) can describe flows with numeric properties such as MTU (maximum transmission unit), RTT (round trip time), traversal order, and bandwidth allocation over parallel paths; (2) when using Boolean predicate constraints for the constraint system, TRAFFIC(X) can describe routing policies of an IP network. These examples illustrate how to use the customized type system.