24,790 research outputs found
Prospects and limitations of full-text index structures in genome analysis
The combination of incessant advances in sequencing technology producing large amounts of data and innovative bioinformatics approaches, designed to cope with this data flood, has led to new interesting results in the life sciences. Given the magnitude of sequence data to be processed, many bioinformatics tools rely on efficient solutions to a variety of complex string problems. These solutions include fast heuristic algorithms and advanced data structures, generally referred to as index structures. Although the importance of index structures is generally known to the bioinformatics community, the design and potency of these data structures, as well as their properties and limitations, are less understood. Moreover, the last decade has seen a boom in the number of variant index structures featuring complex and diverse memory-time trade-offs. This article brings a comprehensive state-of-the-art overview of the most popular index structures and their recently developed variants. Their features, interrelationships, the trade-offs they impose, but also their practical limitations, are explained and compared
Optimum Search Schemes for Approximate String Matching Using Bidirectional FM-Index
Finding approximate occurrences of a pattern in a text using a full-text
index is a central problem in bioinformatics and has been extensively
researched. Bidirectional indices have opened new possibilities in this regard
allowing the search to start from anywhere within the pattern and extend in
both directions. In particular, use of search schemes (partitioning the pattern
and searching the pieces in certain orders with given bounds on errors) can
yield significant speed-ups. However, finding optimal search schemes is a
difficult combinatorial optimization problem.
Here for the first time, we propose a mixed integer program (MIP) capable to
solve this optimization problem for Hamming distance with given number of
pieces. Our experiments show that the optimal search schemes found by our MIP
significantly improve the performance of search in bidirectional FM-index upon
previous ad-hoc solutions. For example, approximate matching of 101-bp Illumina
reads (with two errors) becomes 35 times faster than standard backtracking.
Moreover, despite being performed purely in the index, the running time of
search using our optimal schemes (for up to two errors) is comparable to the
best state-of-the-art aligners, which benefit from combining search in index
with in-text verification using dynamic programming. As a result, we anticipate
a full-fledged aligner that employs an intelligent combination of search in the
bidirectional FM-index using our optimal search schemes and in-text
verification using dynamic programming outperforms today's best aligners. The
development of such an aligner, called FAMOUS (Fast Approximate string Matching
using OptimUm search Schemes), is ongoing as our future work
Indexing large genome collections on a PC
Motivation: The availability of thousands of invidual genomes of one species
should boost rapid progress in personalized medicine or understanding of the
interaction between genotype and phenotype, to name a few applications. A key
operation useful in such analyses is aligning sequencing reads against a
collection of genomes, which is costly with the use of existing algorithms due
to their large memory requirements.
Results: We present MuGI, Multiple Genome Index, which reports all
occurrences of a given pattern, in exact and approximate matching model,
against a collection of thousand(s) genomes. Its unique feature is the small
index size fitting in a standard computer with 16--32\,GB, or even 8\,GB, of
RAM, for the 1000GP collection of 1092 diploid human genomes. The solution is
also fast. For example, the exact matching queries are handled in average time
of 39\,s and with up to 3 mismatches in 373\,s on the test PC with
the index size of 13.4\,GB. For a smaller index, occupying 7.4\,GB in memory,
the respective times grow to 76\,s and 917\,s.
Availability: Software and Suuplementary material:
\url{http://sun.aei.polsl.pl/mugi}
Efficient Genomic Interval Queries Using Augmented Range Trees
Efficient large-scale annotation of genomic intervals is essential for
personal genome interpretation in the realm of precision medicine. There are 13
possible relations between two intervals according to Allen's interval algebra.
Conventional interval trees are routinely used to identify the genomic
intervals satisfying a coarse relation with a query interval, but cannot
support efficient query for more refined relations such as all Allen's
relations. We design and implement a novel approach to address this unmet need.
Through rewriting Allen's interval relations, we transform an interval query to
a range query, then adapt and utilize the range trees for querying. We
implement two types of range trees: a basic 2-dimensional range tree (2D-RT)
and an augmented range tree with fractional cascading (RTFC) and compare them
with the conventional interval tree (IT). Theoretical analysis shows that RTFC
can achieve the best time complexity for interval queries regarding all Allen's
relations among the three trees. We also perform comparative experiments on the
efficiency of RTFC, 2D-RT and IT in querying noncoding element annotations in a
large collection of personal genomes. Our experimental results show that 2D-RT
is more efficient than IT for interval queries regarding most of Allen's
relations, RTFC is even more efficient than 2D-RT. The results demonstrate that
RTFC is an efficient data structure for querying large-scale datasets regarding
Allen's relations between genomic intervals, such as those required by
interpreting genome-wide variation in large populations.Comment: 4 figures, 4 table
Software Grand Exposure: SGX Cache Attacks Are Practical
Side-channel information leakage is a known limitation of SGX. Researchers
have demonstrated that secret-dependent information can be extracted from
enclave execution through page-fault access patterns. Consequently, various
recent research efforts are actively seeking countermeasures to SGX
side-channel attacks. It is widely assumed that SGX may be vulnerable to other
side channels, such as cache access pattern monitoring, as well. However, prior
to our work, the practicality and the extent of such information leakage was
not studied.
In this paper we demonstrate that cache-based attacks are indeed a serious
threat to the confidentiality of SGX-protected programs. Our goal was to design
an attack that is hard to mitigate using known defenses, and therefore we mount
our attack without interrupting enclave execution. This approach has major
technical challenges, since the existing cache monitoring techniques experience
significant noise if the victim process is not interrupted. We designed and
implemented novel attack techniques to reduce this noise by leveraging the
capabilities of the privileged adversary. Our attacks are able to recover
confidential information from SGX enclaves, which we illustrate in two example
cases: extraction of an entire RSA-2048 key during RSA decryption, and
detection of specific human genome sequences during genomic indexing. We show
that our attacks are more effective than previous cache attacks and harder to
mitigate than previous SGX side-channel attacks
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