Shouji: a fast and efficient pre-alignment filter for sequence alignment.

MOTIVATION: The ability to generate massive amounts of sequencing data continues to overwhelm the processing capability of existing algorithms and compute infrastructures. In this work, we explore the use of hardware/software co-design and hardware acceleration to significantly reduce the execution time of short sequence alignment, a crucial step in analyzing sequenced genomes. We introduce Shouji, a highly parallel and accurate pre-alignment filter that remarkably reduces the need for computationally-costly dynamic programming algorithms. The first key idea of our proposed pre-alignment filter is to provide high filtering accuracy by correctly detecting all common subsequences shared between two given sequences. The second key idea is to design a hardware accelerator that adopts modern field-programmable gate array (FPGA) architectures to further boost the performance of our algorithm. RESULTS: Shouji significantly improves the accuracy of pre-alignment filtering by up to two orders of magnitude compared to the state-of-the-art pre-alignment filters, GateKeeper and SHD. Our FPGA-based accelerator is up to three orders of magnitude faster than the equivalent CPU implementation of Shouji. Using a single FPGA chip, we benchmark the benefits of integrating Shouji with five state-of-the-art sequence aligners, designed for different computing platforms. The addition of Shouji as a pre-alignment step reduces the execution time of the five state-of-the-art sequence aligners by up to 18.8×. Shouji can be adapted for any bioinformatics pipeline that performs sequence alignment for verification. Unlike most existing methods that aim to accelerate sequence alignment, Shouji does not sacrifice any of the aligner capabilities, as it does not modify or replace the alignment step. AVAILABILITY AND IMPLEMENTATION: https://github.com/CMU-SAFARI/Shouji. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

GRIM-Filter: Fast seed location filtering in DNA read mapping using processing-in-memory technologies.

BACKGROUND: Seed location filtering is critical in DNA read mapping, a process where billions of DNA fragments (reads) sampled from a donor are mapped onto a reference genome to identify genomic variants of the donor. State-of-the-art read mappers 1) quickly generate possible mapping locations for seeds (i.e., smaller segments) within each read, 2) extract reference sequences at each of the mapping locations, and 3) check similarity between each read and its associated reference sequences with a computationally-expensive algorithm (i.e., sequence alignment) to determine the origin of the read. A seed location filter comes into play before alignment, discarding seed locations that alignment would deem a poor match. The ideal seed location filter would discard all poor match locations prior to alignment such that there is no wasted computation on unnecessary alignments. RESULTS: We propose a novel seed location filtering algorithm, GRIM-Filter, optimized to exploit 3D-stacked memory systems that integrate computation within a logic layer stacked under memory layers, to perform processing-in-memory (PIM). GRIM-Filter quickly filters seed locations by 1) introducing a new representation of coarse-grained segments of the reference genome, and 2) using massively-parallel in-memory operations to identify read presence within each coarse-grained segment. Our evaluations show that for a sequence alignment error tolerance of 0.05, GRIM-Filter 1) reduces the false negative rate of filtering by 5.59x-6.41x, and 2) provides an end-to-end read mapper speedup of 1.81x-3.65x, compared to a state-of-the-art read mapper employing the best previous seed location filtering algorithm. CONCLUSION: GRIM-Filter exploits 3D-stacked memory, which enables the efficient use of processing-in-memory, to overcome the memory bandwidth bottleneck in seed location filtering. We show that GRIM-Filter significantly improves the performance of a state-of-the-art read mapper. GRIM-Filter is a universal seed location filter that can be applied to any read mapper. We hope that our results provide inspiration for new works to design other bioinformatics algorithms that take advantage of emerging technologies and new processing paradigms, such as processing-in-memory using 3D-stacked memory devices.

GateKeeper: a new hardware architecture for accelerating pre-alignment in DNA short read mapping.

MOTIVATION: High throughput DNA sequencing (HTS) technologies generate an excessive number of small DNA segments -called short reads- that cause significant computational burden. To analyze the entire genome, each of the billions of short reads must be mapped to a reference genome based on the similarity between a read and 'candidate' locations in that reference genome. The similarity measurement, called alignment, formulated as an approximate string matching problem, is the computational bottleneck because: (i) it is implemented using quadratic-time dynamic programming algorithms and (ii) the majority of candidate locations in the reference genome do not align with a given read due to high dissimilarity. Calculating the alignment of such incorrect candidate locations consumes an overwhelming majority of a modern read mapper's execution time. Therefore, it is crucial to develop a fast and effective filter that can detect incorrect candidate locations and eliminate them before invoking computationally costly alignment algorithms. RESULTS: We propose GateKeeper, a new hardware accelerator that functions as a pre-alignment step that quickly filters out most incorrect candidate locations. GateKeeper is the first design to accelerate pre-alignment using Field-Programmable Gate Arrays (FPGAs), which can perform pre-alignment much faster than software. When implemented on a single FPGA chip, GateKeeper maintains high accuracy (on average >96%) while providing, on average, 90-fold and 130-fold speedup over the state-of-the-art software pre-alignment techniques, Adjacency Filter and Shifted Hamming Distance (SHD), respectively. The addition of GateKeeper as a pre-alignment step can reduce the verification time of the mrFAST mapper by a factor of 10. AVAILABILITY AND IMPLEMENTATION: https://github.com/BilkentCompGen/GateKeeper. CONTACT: mohammedalser@bilkent.edu.tr or onur.mutlu@inf.ethz.ch or calkan@cs.bilkent.edu.tr. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Gliosarcoma case report and review of the literature.

Gliosarcoma is an unusual subtype of glioblastoma multiforme. Its characteristic features are biphasic configuration, constituting a definite, separate glial and sarcomatous differentiation, on histological evaluation. Herein, we present a rare case of Gliosarcoma that had presented only once in our center in last 13 years. A 60 years old, diabetic, hypertensive male patient came to e emergency department with disturbed level of consciousness and right sided hemiplegia which was progressive over four days. On examination he was, conscious, unoriented in time, person or place, his mouth deviated to left and vitally stable. After initial evaluation, CT scan and MRI were advised. These showed a complex left parieto-occipital heterogeneous mass lesion with cystic and solid components, measuring approximately 5.2x4cm. The mass lesion was seen displacing the occipital horn anteriorly and inferiorly with probable extension into the lateral ventricular cavity. There was no associated midline shift or definite herniation. The lesion was diagnosed as highly suggestive of brain tumor with a differential diagnosis of glioblastoma multiforme or ependymoma. Blood picture revealed a rapidly increasing level of anemia. Surgical intervention comprising left parieto-occipital craniotomy and near total resection of the tumor was carried out. On histopathological and immunohistochemical evaluation the diagnosis of GS was established. A plan of a combination of adjuvant chemotherapy and radiation was formulated that was however, declined by the family. On regular follow up, the patients clinical state rapidly deteriorated with persistence of seizures and requirement of repeated blood transfusions. The patient finally passed away after eighth months.

Preparation and antibacterial activity of copper and cobalt complexes of 4-chloro-3-nitrobenzoate with a nitrogen donor ligand.

Copper and cobalt complexes with 4-chloro-3-nitrobenzoate (ClNBz) and the nitrogen ligands 1,3-diaminopropane (1,3-DAP) or o-phenylenediamine (o-PDA), were prepared and characterized. The complexes [Cu(ClNBz)2(1,3-DAP)] (1), [Cu(ClNBz)(o-PDA)]Cl (2), [Co(ClNBz)2(1,3-DAP)] (3) and [Co(ClNBz)2(o-PDA)2] (4) were characterized by FTIR, UV-Visible absorption, elemental analysis and thermal analysis. Complex [Cu(ClNBz)(o-PDA)]Cl (2) shows high antibacterial activity as indicated by its ability to inhibit the growth of Staphylococcus aureus, Enterococcus faecalis.

Involvement of mitochondria in acetaminophen-induced apoptosis and hepatic injury: roles of cytochrome c, Bax, Bid, and caspases.

The role of apoptosis in acetaminophen (AAP)-induced hepatic injury was investigated. Six hours after AAP administration to BALB/c mice, a significant loss of hepatic mitochondrial cytochrome c was observed that was similar in extent to the loss observed after in vivo activation of CD95 by antibody treatment. AAP-induced loss of mitochondrial cytochrome c coincided with the appearance in the cytosol of a fragment corresponding to truncated Bid (tBid). At the same time, tBid became detectable in the mitochondrial fraction, and concomitantly, Bax was found translocated to mitochondria. However, AAP failed to activate the execution caspases 3 and 7 as evidenced by a lack of procaspase processing and the absence of an increase in caspase-3-like activity. In contrast, the administration of the pan-inhibitor of caspases, benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone (but not its analogue benzyloxycarbonyl-Phe-Ala-fluoromethylketone) prevented the development of liver injury by AAP and the appearance of apoptotic parenchymal cells. This correlated with the inhibition of the processing of Bid to tBid. The caspase inhibitor failed to prevent both the redistribution of Bax to the mitochondria and the loss of cytochrome c. In conclusion, apoptosis is an important causal event in the initiation of the hepatic injury inflicted by AAP. However, as suggested by the lack of activation of the main execution caspases, apoptosis is not properly executed and degenerates into necrosis.