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Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin-Siris patients (ARID1BCSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive webbased survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1BID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features., We are grateful for the assistance of Pepijn Cox in setting up the website www.arid1bgene.com. This study has made use of data generated by the Human Disease Genes website series, www.humandiseasegenes.com. This work was financially supported by grants from the Netherlands Organisation for Health Research and Development (917-86-319 to B.B.A.d.V., 912-12-109 to B.B.A.d.V.)

The DNA sequencing data analysis pipelines require significant computational resources. In that sense, cloud computing infrastructures appear as a natural choice for this processing. However, the first practical difficulty in reaching the cloud computing services is the transmission of the massive DNA sequencing data from where they are produced to where they will be processed. The daily practice here begins with compressing the data in FASTQ file format, and then sending these data via fast data transmission protocols. In this study, we address the weaknesses in that daily practice and present a new system architecture that incorporates the computational resources available on the client side while dynamically adapting itself to the available bandwidth. Our proposal considers the real-life scenarios, where the bandwidth of the connection between the parties may fluctuate, and also the computing power on the client side may be of any size ranging from moderate personal computers to powerful workstations. The proposed architecture aims at utilizing both the communication bandwidth and the computing resources for satisfying the ultimate goal of reaching the results as early as possible. We present a prototype implementation of the proposed architecture, and analyze several real-life cases, which provide useful insights for the sequencing centers, especially on deciding when to use a cloud service and in what conditions.

MRPS22 gene defect is a very rare newly discovered mitochondrial disorder. We report a 4-month-old severely affected male infant with MRPS22 mutation. Whole exome sequencing revealed a novel homozygous splicing mutation c.339 + 5 G > A in MRPS22 gene. He has mild dysmorphism, hypotonia, developmental delay but not hypertrophic cardiomyopathy and tubulopathy which differ from other majority of reported patients. Therefore, hypertrophic cardiomyopathy and tubulopathy may not be considered as constant features of MRPS22. With this case report, we also present first symmetrical bilateral brainstem and medial thalamic lesions, and cerebellar and cerebral atrophy on a brain MR imaging follow-up of ten months.

We present a novel multisystem disease in two siblings with clinical features resembling a lysosomal storage disease. These included coarse face, dysostosis multiplex, respiratory difficulty, proteinuria with glomerular foamy cells, neurological involvement with developmental delays, pyramidal signs, and severe chronic anemia. Detailed enzymatic analysis for lysosomal diseases and whole-exome sequencing studies excluded known lysosomal storage diseases in the proband. Subsequently, genome-wide genotyping and exome sequencing analysis of the family indicated two large homozygous regions on chromosomes 5 and 12, and strongly suggested that a homozygous p. R498W missense mutation in the VPS33A gene might be responsible for this novel disease. Segregation analysis in family members and mutation prediction tools' results also supported the damaging effect of the missense mutation on the function of the Vps33a protein, which plays a role in the vesicular transport system. Electron microscopic studies of the cornea of the proband showed findings supportive of dysfunction in vesicular transport. The clinical phenotype and genetic studies support the suggestion that the siblings most probably have a novel disease very likely caused by a VPS33A gene defect.

Hereditary spastic paraplegias (HSPs) are a group of genetic disorders resulting in pyramidal tract impairment, predominantly in lower limbs. KIF1C gene has recently been identified as one of the genetic causes of HSP and associated with pure or complicated HSP. We present three patients with complicated HSP from two unrelated families, who had early onset progressive cerebellar signs and developed pyramidal tract signs during follow-up. Whole exome sequencing in these patients followed by segregation analysis identified novel truncating KIFIC mutations (c.463C> T; p.R155* and c.2478delA; p.A1a828Argfs*13). Neuroimaging findings showed cerebral and upper cervical spinal atrophy, bilateral symmetrical pyramidal tract involvement, and focal cerebral white matter lesions. Patients with KIFIC mutations may present with cerebellar signs and pyramidal findings may emerge later, therefore complicated HSP should be considered in the differential diagnosis of unidentified cases with cerebellar dysfunction. (C) 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article.

Coffin-Siris syndrome (CSS) (MIM 135900) is characterized by developmental delay, severe speech impairment, distinctive facial features, hypertrichosis, aplasia or hypoplasia of the distal phalanx or nail of the fifth digit and agenesis of the corpus callosum. Recently, it was shown that mutations in the ARID1B gene are the main cause of CSS, accounting for 76% of identified mutations. Here, we report a 15 year-old female patient who was admitted to our clinic with seizures, speech problems, dysmorphic features, bilaterally big, large thumb, cafe-au-lait (CAL) spots, obesity and hyperinsulinism. First, the patient was thought to have an association of neurofibromatosis and Rubinstein Taybi syndrome. Because of the large size of the NF1 gene for neurofibromatosis and CREBBP gene for Rubinstein Taybi syndrome, whole exome sequence analysis (WES) was conducted and a novel ARID1B mutation was identified. The proband WES test identified a novel heterozygous frameshift mutation c.3394_3395insTA in exon 13 of ARID1B (NM_017519.2) predicting a premature stop codon p.(Tyr1132Leufs*67). Sanger sequencing confirmed the heterozygous c.3394_3395insTA mutation in the proband and that it was not present in her parents indicating de novo mutation. Further investigation and new cases will help to understand this phenomenon better.

This work was supported by the Republic of Turkey Ministry of Development Infrastructure Grant (no. 2011K120020 to B.Y., A.O.B., O.F.G. and M.S.S.) and BILGEM-TUBITAK (the Scientific and Technological Research Council of Turkey) (grant no. T439000 to B.Y., A.O.B., O.F.G. and M.S.S.)., POC1A encodes a WD repeat protein localizing to centrioles and spindle poles and is associated with short stature, onychodysplasia, facial dysmorphismand hypotrichosis (SOFT) syndrome. These main features are related to the defect in cell proliferation of chondrocytes in growth plate. In the current study, we aimed at identifying the molecular basis of two patients with primordial dwarfism (PD) in a single family through utilization of whole-exome sequencing. A novel homozygous p.T120A missense mutation was detected in POC1A in both patients, a known causative gene of SOFT syndrome, and confirmed using Sanger sequencing. To test the pathogenicity of the detected mutation, primary fibroblast cultures obtained from the patients and a control individual were used. For evaluating the global gene expression profile of cells carrying p.T120A mutation in POC1A, we performed the gene expression array and compared their expression profiles to those of control fibroblast cells. The gene expression array analysis showed that 4800 transcript probes were significantly deregulated in cells with p.T120A mutation in comparison to the control. GO term association results showed that deregulated genes are mostly involved in the extracellular matrix and cytoskeleton. Furthermore, the p.T120A missense mutation in POC1A caused the formation of abnormal mitotic spindle structure, including supernumerary centrosomes, and changes in POC1A were accompanied by alterations in another centrosome-associated WD repeat protein p80-katanin. As a result, we identified a novel mutation in POC1A of patients with PD and showed that this mutation causes the formation of multiple numbers of centrioles and multipolar spindles with abnormal chromosome arrangement., Republic of Turkey Ministry of Development Infrastructure [2011K120020]; BILGEM-TUBITAK (the Scientific and Technological Research Council of Turkey) [T439000]

Pediatric-onset ataxias often present clinically as developmental delay and intellectual disability, with prominent cerebellar atrophy as a key neuroradiographic finding. Here we describe a new clinically distinguishable recessive syndrome in 12 families with cerebellar atrophy together with ataxia, coarsened facial features and intellectual disability, due to truncating mutations in the sorting nexin gene SNX14, encoding a ubiquitously expressed modular PX domain-containing sorting factor. We found SNX14 localized to lysosomes and associated with phosphatidylinositol (3,5)-bisphosphate, a key component of late endosomes/lysosomes. Patient-derived cells showed engorged lysosomes and a slower autophagosome clearance rate upon autophagy induction by starvation. Zebrafish morphants for snx14 showed dramatic loss of cerebellar parenchyma, accumulation of autophagosomes and activation of apoptosis. Our results characterize a unique ataxia syndrome due to biallelic SNX14 mutations leading to lysosome-autophagosome dysfunction.

Summary: Due to the big data produced by next-generation sequencing studies, there is an evident need for methods to extract the valuable information gathered from these experiments. In this work, we propose GeneCOST, a novel scoring-based method to evaluate every gene for their disease association. Without any prior filtering and any prior knowledge, we assign a disease likelihood score to each gene in correspondence with their variations. Then, we rank all genes based on frequency, conservation, pedigree and detailed variation information to find out the causative reason of the disease state. We demonstrate the usage of GeneCOST with public and real life Mendelian disease cases including recessive, dominant, compound heterozygous and sporadic models. As a result, we were able to identify causative reason behind the disease state in top rankings of our list, proving that this novel prioritization framework provides a powerful environment for the analysis in genetic disease studies alternative to filtering-based approaches. Availability and implementation: GeneCOST software is freely available at www.igbam.bilgem.tubitak.gov.tr/en/softwares/genecost-en/index.html. Contact: buozer@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online.

Cerebrofaciothoracic dysplasia (CFT) (OMIM #213980) is a multiple congenital anomaly and intellectual disability syndrome involving the cranium, face, and thorax. The characteristic features are cranial involvement with macrocrania at birth, brachycephaly, various CT/MRI findings including hypoplasia of corpus callosum, enlargement of septum pellicidum, and diffuse hypodensity of the grey matter, flat face, hypertelorism, cleft lip and cleft palate, low-set, posteriorly rotated ears, short neck, and multiple costal and vertebral anomalies. The underlying genetic defect remains unknown. Using combination of homozygosity mapping and whole-exome sequencing, we identified a homozygous nonsense founder mutation, p.Arg87Ter (c.259 C>T), in the human transmembrane and coiled-coil domains protein 1 (TMCO1) in four out of five families of Turkish origin. The entire critical region on chromosome 1q24 containing TMCO1 was excluded in the fifth family with characteristic findings of CFT providing evidence for genetic heterogeneity of CFT spectrum. Another founder TMCO1 mutation has recently been reported to cause a unique genetic condition, TMCO1-defect syndrome (OMIM #614132). TMCO1-defect syndrome shares many features with CFT. This study supports the fact that TMCO1-defect syndrome, initially thought to represent a distinct disorder, indeed belongs to the genetically heterogeneous CFT dysplasia spectrum. (c) 2013 Wiley Periodicals, Inc.

This study aimed to identify PYGM mutations in patients with McArdle disease from Turkey by next generation sequencing (NGS). Genomic DNA was extracted from the blood of the McArdle patients (n = 67) and unrelated healthy volunteers (n = 53). The PYGM gene was sequenced with NGS and the observed mutations were validated by direct Sanger sequencing. A diagnostic algorithm was developed for patients with suspected McArdle disease. A total of 16 deleterious PYGM mutations were identified, of which 5 were novel, including 1 splice-site donor, 1 frame-shift, and 3 non-synonymous variants. The p.Met1Val (27-patients/11-families) was the most common PYGM mutation, followed by p.Arg576* (6/4), c.1827+7A>G (5/4), c.772+2_3delTG (5/3), p.Phe710del (4/2), p.Lys754Asnfs (2/1), and p.Arg50* (1/1). A molecular diagnostic flowchart is proposed for the McArdle patients in Turkey, covering the 6 most common PYGM mutations found in Turkey as well as the most common mutation in Europe. The diagnostic algorithm may alleviate the need for muscle biopsies in 77.6% of future patients. A prevalence of any of the mutations to a geographical region in Turkey was not identified. Furthermore, the NGS approach to sequence the entire PYGM gene was successful in detecting a common missense mutation and discovering novel mutations in this population study. (C) 2017 Elsevier B.V. All rights reserved.

WOS: 000405288400031, PubMed ID: 28407396, Stromme syndrome is a rare genetic disorder characterized by microcephaly, anterior ocular chamber anomalies, and "apple peel" type jejunal atresia. Here, we report a Stromme syndrome family with two affected siblings with a homozygous truncating frameshift mutation in CENPF. A 3-month-old girl was hospitalized due to prenatally diagnosed microcephaly, microphthalmia, and dysmorphological features. The history of a previous child with the same findings in addition to "apple peel" intestinal atresia had been noted. Regarding the clinical features of both affected siblings, a diagnosis of Stromme syndrome was established. Exome-sequencing of these two cases showed the homozygous mutation (c.5912_5913insA)/(p.T1974Nfs*9) in CENPF. While confirmation of this gene being responsible for Stromme syndrome was pending our results, Filges et al. reported that CENPF was indeed underlying the reason for Stromme syndrome. This is the second case report identifying CENPF mutation as the cause of Stromme syndrome., Republic of Turkey Ministry of Development Infrastructure GrantTurkiye Cumhuriyeti Kalkinma Bakanligi [215S179]; BILGEM-TUBITAK (The Scientific and Technological Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [T439000], Republic of Turkey Ministry of Development Infrastructure Grant, Grant number: 215S179; BILGEM-TUBITAK (The Scientific and Technological Research Council of Turkey), Grant number: T439000

Next Generation DNA Sequencing technologies offer ultra high sequencing throughput for very low prices. The increase in throughput and diminished costs open up new research areas. Moreover, number of clinicians utilizing DNA sequencing keeps growing. One of the main concern for researchers and clinicians who are adopting these platforms is their sequencing accuracy. We compared three of the most commonly used Next Generation Sequencing platforms; Ion Torrent from Life Technologies, GS FLX+ from Roche and HiSeq 2000 from Illumina.

Çalışmada 21 yazar bulunmaktadır. Bu yazarlardan sadece Bursa Uludağ Üniversitesi mensuplarının girişleri yapılmıştır. Vascular malformations are non-neoplastic expansions of blood vessels that arise due to errors during angiogenesis. They are a heterogeneous group of sporadic or inherited vascular disorders characterized by localized lesions of arteriovenous, capillary, or lymphatic origin. Vascular malformations that occur inside bone tissue are rare. Herein, we report loss-of-function mutations in ELMO2 (which translates extracellular signals into cellular movements) that are causative for autosomal-recessive intraosseous vascular malformation (VMOS) in five different families. Individuals with VMOS suffer from life-threatening progressive expansion of the jaw, craniofacial, and other intramembranous bones caused by malformed blood vessels that lack a mature vascular smooth muscle layer. Analysis of primary fibroblasts from an affected individual showed that absence of ELMO2 correlated with a significant downregulation of binding partner DOCK1, resulting in deficient RAC1-dependent cell migration. Unexpectedly, elmo2-knockout zebrafish appeared phenotypically normal, suggesting that there might be human-specific ELMO2 requirements in bone vasculature homeostasis or genetic compensation by related genes. Comparative phylogenetic analysis indicated that elmo2 originated upon the appearance of intramembranous bones and the jaw in ancestral vertebrates, implying that elmo2 might have been involved in the evolution of these novel traits. The present findings highlight the necessity of ELMO2 for maintaining vascular integrity, specifically in intramembranous bones. CRANIRARE consortium - R07197KS Strategic Positioning Fund for Genetic Orphan Diseases Agency for Science Technology & Research (A*STAR) Hacettepe Üniversitesi- 00-02-101-009 / 03-D07-101-001

Date of Conference: 10-12 September, 2015 Conference name: CIBB: International Meeting on Computational Intelligence Methods for Bioinformatics and Biostatistics - 12th International Meeting, CIBB 2015 Accurate de novo assembly using short reads generated by next generation sequencing technologies is still an open problem. Although there are several assembly algorithms developed for data generated with different sequencing technologies, and some that can make use of hybrid data, the assemblies are still far from being perfect. There is still a need for computational approaches to improve draft assemblies. Here we propose a new method to correct assembly mistakes when there are multiple types of data generated using different sequencing technologies that have different strengths and biases. We exploit the assembly of highly accurate short reads to correct the contigs obtained from less accurate long reads. We apply our method to Illumina, 454, and Ion Torrent data, and also compare our results with existing hybrid assemblers, Celera and Masurca. © Springer International Publishing Switzerland 2016.

Background Fasciola hepatica causes chronic liver disease, fasciolosis, leading to significant losses in the livestock economy and concerns for human health in many countries. The identification of F. hepatica genes involved in the parasite’s virulence through modulation of host immune system is utmost important to comprehend evasion mechanisms of the parasite and develop more effective strategies against fasciolosis. In this study, to identify the parasite’s putative virulence genes which are associated with host immunomodulation, we explored whole transcriptome of an adult F. hepatica using current transcriptome profiling approaches integrated with detailed in silico analyses. In brief, the comparison of the parasite transcripts with the specialised public databases containing sequence data of non-parasitic organisms (Dugesiidae species and Caenorhabditis elegans) or of numerous pathogens and investigation of the sequences in terms of nucleotide evolution (directional selection) and cytokine signaling relation were conducted. Results NGS of the whole transcriptome resulted in 19,534,766 sequence reads, yielding a total of 40,260 transcripts (N50 = 522 bp). A number of the parasite transcripts (n = 1,671) were predicted to be virulence-related on the basis of the exclusive homology with the pathogen-associated data, positive selection or relationship with cytokine signaling. Of these, a group of the virulence-related genes (n = 62), not previously described, were found likely to be associated with immunomodulation based on in silico functional categorisation, showing significant sequence similarities with various immune receptors (i.e. MHC I class, TGF-β receptor, toll/interleukin-1 receptor, T-cell receptor, TNF receptor, and IL-18 receptor accessory protein), cytokines (i.e. TGF-β, interleukin-4/interleukin-13 and TNF-α), cluster of differentiations (e.g. CD48 and CD147) or molecules associated with other immunomodulatory mechanisms (such as regulation of macrophage activation). Some of the genes (n = 5) appeared to be under positive selection (Ka/Ks > 1), imitating proteins associated with cytokine signaling (through sequence homologies with thrombospondin type 1, toll/interleukin-1 receptor, TGF-β receptor and CD147). Conclusions With a comparative transcriptome profiling approach, we have identified a number of potential immunomodulator genes of F. hepatica (n = 62), which are firstly described here, could be employed for the development of better strategies (including RNAi) in the battle against both zoonotically and economically important disease, fasciolosis. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-1539-8) contains supplementary material, which is available to authorized users.

We report an association between a new causative gene and spastic paraplegia, which is a genetically heterogeneous disorder. Clinical phenotyping of one consanguineous family followed by combined homozygosity mapping and whole-exome sequencing analysis. Three patients from the same family shared common features of progressive complicated spastic paraplegia. They shared a single homozygous stretch area on chromosome 6. Whole-exome sequencing revealed a homozygous mutation (c.853\_871del19) in the gene coding the kinesin light chain 4 protein (KLC4). Meanwhile, the unaffected parents and two siblings were heterozygous and one sibling was homozygous wild type. The 19 bp deletion in exon 6 generates a stop codon and thus a truncated messenger RNA and protein. The association of a KLC4 mutation with spastic paraplegia identifies a new locus for the disease.

A consanguineous family from Turkey having two children with intellectual disability exhibiting myoclonic, febrile and other generalized seizures was recruited to identify the genetic origin of these phenotypes. A combined approach of SNP genotyping and exome sequencing was employed both to screen genes associated with Dravet syndrome and to detect homozygous variants. Analysis of exome data was extended further to identify compound heterozygosity. Herein, we report identification of two paternally inherited genetic variants in SCN1A (rs121917918; p.R101Q and p.I1576T), one of which was previously implicated in Dravet syndrome. Interestingly, the previously reported clinical variant (rs121917918; p.R101Q) displayed mosaicisnn in the blood and saliva of the father. The study supported the genetic diagnosis of affected children as Dravet syndrome possibly due to the combined effect of one clinically associated (rs121917918; p.R101Q) and one novel (p.I1576T) variants in SCN1A gene. This finding is important given that heterozygous variants may be overlooked in standard exome scans of consanguineous families. Thus, we are presenting an interesting example, where the inheritance of the condition may be misinterpreted as recessive and identical by descent due to consanguinity and mosaicism in one of the parents. (C) 2015 Elsevier B.V. All rights reserved.

This work was supported by The Republic of Turkey Ministry of Development Infrastructure Grant (no: 20111(120020 to MSS, BE) and BILGEM - TUBITAK (The Scientific and Technological Research Council of Turkey) (grant no: T439000 to MSS, BE)., Usher syndrome is a clinically and genetically heterogeneous autosomal recessive inherited disorder accompanied by hearing loss and retinitis pigmentosa (RP). Since the associated genes are various and quite large, we utilized whole-exome sequencing (WES) as a diagnostic tool to identify the molecular basis of Usher syndrome. DNA from a 12-year-old male diagnosed with Usher syndrome was analyzed by WES. Mutations detected were confirmed by Sanger sequencing. The pathogenicity of these mutations was determined by in silico analysis. A maternally inherited deleterious frameshift mutation, c.14439_14454del in exon 66 and a paternally inherited non-sense c.10830G>A stop-gain SNV in exon 55 of USH2A were found as two novel compound heterozygous mutations. Both of these mutations disrupt the C terminal of USH2A protein. As a result, WES revealed two novel compound heterozygous mutations in a Turkish USH2A patient. This approach gave us an opportunity to have an appropriate diagnosis and provide genetic counseling to the family within a reasonable rime., Republic of Turkey Ministry of Development Infrastructure Grant [2011K120020]; BILGEM - TUBITAK (The Scientific and Technological Research Council of Turkey) [T439000]

Cataloged from PDF version of article. Background Human de novo single-nucleotide variation (SNV) rate is estimated to range between 0.82-1.70x10(-8) mutations per base per generation. However, contribution of early postzygotic mutations to the overall human de novo SNV rate is unknown. Methods We performed deep whole-genome sequencing (more than 30-fold coverage per individual) of the whole-blood-derived DNA samples of a healthy monozygotic twin pair and their parents. We examined the genotypes of each individual simultaneously for each of the SNVs and discovered de novo SNVs regarding the timing of mutagenesis. Putative de novo SNVs were validated using Sanger-based capillary sequencing. Results We conservatively characterised 23 de novo SNVs shared by the twin pair, 8 de novo SNVs specific to twin I and 1 de novo SNV specific to twin II. Based on the number of de novo SNVs validated by Sanger sequencing and the number of callable bases of each twin, we calculated the overall de novo SNV rate of 1.31x10(-8) and 1.01x10(-8) for twin I and twin II, respectively. Of these, rates of the early postzygotic de novo SNVs were estimated to be 0.34x10(-8) for twin I and 0.04x10(-8) for twin II. Conclusions Early postzygotic mutations constitute a substantial proportion of de novo mutations in humans. Therefore, genome mosaicism resulting from early mitotic events during embryogenesis is common and could substantially contribute to the development of diseases.

WOS: 000337616100009 PubMed ID: 24733753 Fasciola hepatica is a trematode helminth causing a damaging disease, fasciolosis, in ruminants and humans. Comprehensive proteomic studies broaden our knowledge of the parasite's protein profile, and provide new insights into the development of more effective strategies to deal with fasciolosis. The objective of this study was to generate a comprehensive profile of F. hepatica proteins expressed during the chronic stage of infection in cattle by building on previous efforts in this area. The approach included an improved sample preparation procedure for surface and internal layers of the parasite, the application of nano-UPLC-ESI-qTOF-MS (nano-ultra-performance LC and ESI quadrupole TOF MS) integrated with different acquisition methods and in silico database search against various protein databases and a transcript database including a new assembly of publically available EST. Of a total of 776 identified proteins, 206 and 332 were specific to the surface and internal layers of the parasite, respectively. Furthermore, 238 proteins were common to both layers, with comparative differences of 172 proteins detected. Specific proteins not previously identified in F. hepatica, but shown to be immunomodulatory or potential drug targets for other parasites, are discussed.

Summary: In consanguineous families, as a result of inheriting the same genomic segments through both parents, the individuals have stretches of their genomes that are homozygous. This situation leads to the prevalence of recessive diseases among the members of these families. Homozygosity mapping is based on this observation, and in consanguineous families, several recessive disease genes have been discovered with the help of this technique. The researchers typically use single nucleotide polymorphism arrays to determine the homozygous regions and then search for the disease gene by sequencing the genes within this candidate disease loci. Recently, the advent of next-generation sequencing enables the concurrent identification of homozygous regions and the detection of mutations relevant for diagnosis, using data from a single sequencing experiment. In this respect, we have developed a novel tool that identifies homozygous regions using deep sequence data. Using *.vcf (variant call format) files as an input file, our program identifies the majority of homozygous regions found by microarray single nucleotide polymorphism genotype data. Availability and implementation: HomSI software is freely available at www.igbam.bilgem.tubitak.gov.tr/softwares/HomSI, with an online manual. Contact: bakirburcu@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online.

In the current study, a novel electrode array and integrated microfluidics have been designed and characterised in order to create a sensor chip which is not only easy, rapid and cheaper to produce but also have a smaller imprint and good electrochemical sensing properties. The current study includes the assessment of the effects of an Au quasi-reference electrode and the use of shared reference/counter electrodes for the array, in order to obtain a small array that can be produced using a fine metal mask. In the study, it is found that when Au is used as the quasi-reference electrode, the arrays with shared reference and counter electrodes result in faster electron transfer kinetics and prevent the potential change with respect to scan rate, and hence is advantageous with respect to conventional electrodes. In addition, the resulting novel electrode array has been shown to result in higher current density (10.52 µA/cm2; HRP detection assay) and measured diffusion coefficient (14.40×10−12 cm2/s; calculated from the data of cyclic voltammetry with 1 mM potassium ferricyanide) with respect to conventional electrodes tested in the study. Using the new electrode arrays, the detection limits obtained from horse radish peroxidase (HRP) and bisphenol A assays were 12.5 ng/ml (2.84×10−10 M ) and 10 ng/ml (44×10−9 M), respectively. Performing the HRP detection assay in a flow injection system using array integrated microfluidics provided 25 times lower detection limit (11.36×10−12 M), although Ti has been used as electrode material instead of Au. In short, incorporation of this new electrode array to lab-on-a-chip or MEMs (micro-electro mechanic systems) technologies may pave the way for easy to use automated biosensing devices that could be used for a variety of applications from diagnostics to environmental monitoring, and studies will continue to move forward in this direction.

Smith Waterman Algorithm is a widely used tool in bioinformatics. It aligns reads to a reference in whole genome sequencing. Mapping millions of sequences reads to a reference is a computationally expensive operation. Here, accuracy and performance are two important aspects of the process. Therefore, FPGA based solutions are widely used for this problem. In this study, we try to achieve a better mapping accuracy to achieve optimum alignment using Phred Quality scores of the bases of read sequences while keeping the performance high. We offer a new Smith Waterman processing unit and systolic array based on quality scores.

Smith Waterman Algorithm is a widely used tool in bioinformatics to align reads from aligning to a reference in whole genome sequencing. Mapping millions of sequences read from sequencing is a computationally expensive operation. Accuracy and performance are two important aspects of this process. FPGA based solutions are widely studied. In this paper we tried to achieve a better mapping accuracy for optimum alignment using quality scores of the bases of read sequences while keeping the performance high. We are offering a new Smith Waterman processing unit and systolic array based on quality scores.

Block cipher encryption algorithms generally process on word structures of fixed length such as 8 or 16bits. IDEA is one of the most widely used block ciphers and operates on 16-bit words. Square analysis is a method that exploits the word structure of block ciphers. Some square distinguishers of IDEA are given in previous studies. The best attacks against IDEA use square-like techniques. In this paper, we focus on the square properties of the IDEA block cipher. We consider all fixed word combinations of the plaintext to investigate the structural behavior of the algorithm. We observe that the cipher can be distinguished from a random permutation by fixing one, two or three subblocks of the cipher for 2 and 3 rounds. We find out novel 3-round distinguishers that require 2 16 chosen plaintexts. Furthermore, this approach enables us to propose the first four and five round square distinguishers of IDEA.

The puzzle-assembly problem has many application areas such as restoration and reconstruction of archeological findings, repairing of broken objects, solving jigsaw type puzzles, molecular docking problem, etc. The puzzle pieces usually include not only geometrical shape information but also visual information such as texture, color, and continuity of lines. This paper presents a new approach to the puzzle-assembly problem that is based on using textural features and geometrical constraints. The texture of a band outside the border of pieces is predicted by inpainting and texture synthesis methods. Feature values are derived from these original and predicted images of pieces. An affinity measure of corresponding pieces is defined and alignment of the puzzle pieces is formulated as an optimization problem where the optimum assembly of the pieces is achieved by maximizing the total affinity measure. A Fast Fourier Transform based image registration technique is used to speed up the alignment of the pieces. Experimental results are presented on real and artificial data sets.

The puzzle assembly problem has many application areas such as restoration and reconstruction of archeological findings, repairing of broken objects, solving jigsaw type puzzles, molecular docking problem, etc. The puzzle pieces usually include not only geometrical shape information but also visual information such as texture, color, and continuity of lines. This paper presents a new approach to the puzzle assembly problem that is based on using textural features and geometrical constraints. The texture of a band outside the border of pieces is predicted by inpainting and texture synthesis methods. Feature values are derived from these original and predicted images of pieces. An affinity measure of corresponding pieces is defined and alignment of the puzzle pieces is carried out using an FFT based image registration technique. The optimization of total affinity gives the best assembly of puzzle. Experimental results are presented on real and artificial data sets.

WOS: 000325205700001, PubMed ID: 24073994, Background: Klippel-Feil syndrome (KFS) is characterized by the developmental failure of the cervical spine and has two dominantly inherited subtypes. Affected individuals who are the children of a consanguineous marriage are extremely rare in the medical literature, but the gene responsible for this recessive trait subtype of KFS has recently been reported. Results: We identified a family with the KFS phenotype in which their parents have a consanguineous marriage. Radiological examinations revealed that they carry fusion defects and numerical abnormalities in the cervical spine, scoliosis, malformations of the cranial base, and Sprengel's deformity. We applied whole genome linkage and whole-exome sequencing analysis to identify the chromosomal locus and gene mutated in this family. Whole genome linkage analysis revealed a significant linkage to chromosome 17q12-q33 with a LOD score of 4.2. Exome sequencing identified the G > A p.Q84X mutation in the MEOX1 gene, which is segregated based on pedigree status. Homozygous MEOX1 mutations have reportedly caused a similar phenotype in knockout mice. Conclusions: Here, we report a truncating mutation in the MEOX1 gene in a KFS family with an autosomal recessive trait. Together with another recently reported study and the knockout mouse model, our results suggest that mutations in MEOX1 cause a recessive KFS phenotype in humans., Cumhuriyet University [T-455, T-496], This work is supported by the Scientific Research Project Fund of Cumhuriyet University under project numbers T-455 and T-496.