Quantitative Analysis of Single Nucleotide Polymorphisms within Copy Number Variation

Background Single nucleotide polymorphisms (SNPs) have been used extensively in genetics and epidemiology studies. Traditionally, SNPs that did not pass the Hardy-Weinberg equilibrium (HWE) test were excluded from these analyses. Many investigators have addressed possible causes for departure from HWE, including genotyping errors, population admixture and segmental duplication. Recent large-scale surveys have revealed abundant structural variations in the human genome, including copy number variations (CNVs). This suggests that a significant number of SNPs must be within these regions, which may cause deviation from HWE. Results We performed a Bayesian analysis on the potential effect of copy number variation, segmental duplication and genotyping errors on the behavior of SNPs. Our results suggest that copy number variation is a major factor of HWE violation for SNPs with a small minor allele frequency, when the sample size is large and the genotyping error rate is 0~1%. Conclusions Our study provides the posterior probability that a SNP falls in a CNV or a segmental duplication, given the observed allele frequency of the SNP, sample size and the significance level of HWE testing.

Demand-based Document Dissemination for the World-Wide Web

We analyzed the logs of our departmental HTTP server http://cs-www.bu.edu as well as the logs of the more popular Rolling Stones HTTP server http://www.stones.com. These servers have very different purposes; the former caters primarily to local clients, whereas the latter caters exclusively to remote clients all over the world. In both cases, our analysis showed that remote HTTP accesses were confined to a very small subset of documents. Using a validated analytical model of server popularity and file access profiles, we show that by disseminating the most popular documents on servers (proxies) closer to the clients, network traffic could be reduced considerably, while server loads are balanced. We argue that this process could be generalized so as to provide for an automated demand-based duplication of documents. We believe that such server-based information dissemination protocols will be more effective at reducing both network bandwidth and document retrieval times than client-based caching protocols [2].

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.

On the Performance and Robustness of Managing Reliable Transport Connections

We revisit the problem of connection management for reliable transport. At one extreme, a pure soft-state (SS) approach (as in Delta-t [9]) safely removes the state of a connection at the sender and receiver once the state timers expire without the need for explicit removal messages. And new connections are established without an explicit handshaking phase. On the other hand, a hybrid hard-state/soft-state (HS+SS) approach (as in TCP) uses both explicit handshaking as well as timer-based management of the connection’s state. In this paper, we consider the worst-case scenario of reliable single-message communication, and develop a common analytical model that can be instantiated to capture either the SS approach or the HS+SS approach. We compare the two approaches in terms of goodput, message and state overhead. We also use simulations to compare against other approaches, and evaluate them in terms of correctness (with respect to data loss and duplication) and robustness to bad network conditions (high message loss rate and variable channel delays). Our results show that the SS approach is more robust, and has lower message overhead. On the other hand, SS requires more memory to keep connection states, which reduces goodput. Given memories are getting bigger and cheaper, SS presents the best choice over bandwidth-constrained, error-prone networks.

Object Detection at the Optimal Scale with Hidden State Shape Models

Hidden State Shape Models (HSSMs) [2], a variant of Hidden Markov Models (HMMs) [9], were proposed to detect shape classes of variable structure in cluttered images. In this paper, we formulate a probabilistic framework for HSSMs which provides two major improvements in comparison to the previous method [2]. First, while the method in [2] required the scale of the object to be passed as an input, the method proposed here estimates the scale of the object automatically. This is achieved by introducing a new term for the observation probability that is based on a object-clutter feature model. Second, a segmental HMM [6, 8] is applied to model the "duration probability" of each HMM state, which is learned from the shape statistics in a training set and helps obtain meaningful registration results. Using a segmental HMM provides a principled way to model dependencies between the scales of different parts of the object. In object localization experiments on a dataset of real hand images, the proposed method significantly outperforms the method of [2], reducing the incorrect localization rate from 40% to 15%. The improvement in accuracy becomes more significant if we consider that the method proposed here is scale-independent, whereas the method of [2] takes as input the scale of the object we want to localize.