Assessment of transfer methods for comparative genomics of regulatory networks in Bacteria

Background: Comparative genomics can leverage the vast amount of available genomic sequences to reconstruct and analyze transcriptional regulatory networks in Bacteria, but the efficacy of this approach hinges on the ability to transfer regulatory network information from reference species to the genomes under analysis. Several methods have been proposed to transfer regulatory information between bacterial species, but the paucity and distributed nature of experimental information on bacterial transcriptional networks have prevented their systematic evaluation. Results: We report the compilation of a large catalog of transcription factor-binding sites across Bacteria and its use to systematically benchmark proposed transfer methods across pairs of bacterial species. We evaluate motif- and accuracy-based metrics to assess the results of regulatory network transfer and we identify the precision-recall area-under-the-curve as the best metric for this purpose due to the large class-imbalanced nature of the problem. Methods assuming conservation of the transcription factor-binding motif (motif-based) are shown to substantially outperform those assuming conservation of regulon composition (network-based), even though their efficiency can decrease sharply with increasing phylogenetic distance. Variations of the basic motif-based transfer method do not yield significant improvements in transfer accuracy. Our results indicate that detection of a large enough number of regulated orthologs is critical for network-based transfer methods, but that relaxing orthology requirements does not improve results. Using the transcriptional regulators LexA and Fur as case examples, we also show how DNA-binding domain sequence similarity can yield confounding results as an indicator of transfer efficiency for motif-based methods. Conclusions: Counter to standard practice, our evaluation of metrics to assess the efficiency of methods for regulatory network information transfer reveals that the area under precision-recall (PR) curves is a more precise and informative metric than that of receiver-operating-characteristic (ROC) curves, confirming similar findings in other class-imbalanced settings. Our systematic assessment of transfer methods reveals that simple approaches to both motif- and network-based transfer of regulatory information provide equal or better results than more elaborate methods. We also show that there are not effective predictors of transfer efficacy, substantiating the long-standing practice of manual curation in comparative genomics analyses

Tarihi Huber Köşkü ev sahibine kavuştu

Taha Toros Arşivi, Dosya No: 53-Tarabyaİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

Teknolojik Pedagojik Alan Bilgisi (TPAB) Temelli Harmanlanmış Öğrenme Ortamının Fen Bilimleri Öğretmen Adaylarının TPAB ve Sınıf İçi Uygulama Becerilerine Etkisi

Bu araştırmanın amacı, TPAB temelli harmanlanmış öğrenme ortamının fen bilimleri öğretmen adaylarının gece-gündüz ve mevsimlerin oluşumu konularına ilişkin TPAB ve sınıf içi uygulamaları üzerine etkisini araştırmaktır. Araştırmaya Fen Bilgisi Öğretmenliği programı son sınıfta öğrenim gören 37 öğretmen adayı katılmıştır. Tek grup ön test-son test deneysel desenli bu araştırmada, öğretmen adaylarının TPAB’larını belirlemek için vignette tekniğine dayalı bireysel yarı-yapılandırılmış mülakatlar; sınıf içi uygulamaları için sınıf içi gözlem notları, ders video kayıtları ve sınıf içi gözlem ölçekleri veri toplama aracı olarak kullanılmıştır. Bu araştırmada elde edilen bulgulara göre, araştırmaya katılan öğretmen adaylarının gece-gündüz ve mevsimlerin oluşumu konuları kapsamındaki TPAB ve sınıf içi uygulamalarına ilişkin ön ve son testler arasında son test sonuçları lehine anlamlı bir değişimin olduğu tespit edilmiştir. Bu sonuçlara dayalı olarak, TPAB temelli harmanlanmış öğrenme ortamının fen bilimleri öğretmen adaylarının TPAB ve sınıf içi uygulamalarının gelişiminde önemli bir etkiye sahip olduğu görülmektedir

Flexible comparative genomics of prokaryotic transcriptional regulatory networks

Comparative genomics methods enable the reconstruction of bacterial regulatory networks using available experimental data. In spite of their potential for accelerating research into the composition and evolution of bacterial regulons, few comparative genomics suites have been developed for the automated analysis of these regulatory systems. Available solutions typically rely on precomputed databases for operon and ortholog predictions, limiting the scope of analyses to processed complete genomes, and several key issues such as the transfer of experimental information or the integration of regulatory information in a probabilistic setting remain largely unaddressed. Here we introduce CGB, a flexible platform for comparative genomics of prokaryotic regulons. CGB has few external dependencies and enables fully customized analyses of newly available genome data. The platform automates the merging of experimental information and uses a gene-centered, Bayesian framework to generate and integrate easily interpretable results. We demonstrate its flexibility and power by analyzing the evolution of type III secretion system regulation in pathogenic Proteobacteria and by characterizing the SOS regulon of a new bacterial phylum, the Balneolaeota. Our results demonstrate the applicability of the CGB pipeline in multiple settings. CGB's ability to automatically integrate experimental information from multiple sources and use complete and draft genomic data, coupled with its non-reliance on precomputed databases and its easily interpretable display of gene-centered posterior probabilities of regulation provide users with an unprecedented level of flexibility in launching comparative genomics analyses of prokaryotic transcriptional regulatory networks. The analyses of type III secretion and SOS response regulatory networks illustrate instances of convergent and divergent evolution of these regulatory systems, showcasing the power of formal ancestral state reconstruction at inferring the evolutionary history of regulatory networks

CollecTF : a database of experimentally-validated transcription factor-binding sites in Bacteria

The influx of high-throughput data and the need for complex models to describe the interaction of prokaryotic transcription factors (TF) with their target sites pose new challenges for TF-binding site databases. CollecTF (http://collectf.umbc.edu) compiles data on experimentally validated, naturally occurring TF-binding sites across the Bacteria domain, placing a strong emphasis on the transparency of the curation process, the quality and availability of the stored data and fully customizable access to its records. CollecTF integrates multiple sources of data automatically and openly, allowing users to dynamically redefine binding motifs and their experimental support base. Data quality and currency are fostered in CollecTF by adopting a sustainable model that encourages direct author submissions in combination with in-house validation and curation of published literature. CollecTF entries are periodically submitted to NCBI for integration into RefSeq complete genome records as link-out features, maximizing the visibility of the data and enriching the annotation of RefSeq files with regulatory information. Seeking to facilitate comparative genomics and machine-learning analyses of regulatory interactions, in its initial release CollecTF provides domain-wide coverage of two TF families (LexA and Fur), as well as extensive representation for a clinically important bacterial family, the Vibrionaceae

Varlıkbilim ve süre bilgisini kullanarak web sayfalarından sık görülen desen kümelerinin elde edilmesi

Given set of web pages labeled with ontological items, the level of similarity between two web pages is measured using the level of similarity between ontological items of pages labeled with. Using similarity measure between two pages, degree of similarity between two sequences of web page visits can be calculated as well. Using clustering algorithms, similar frequent sequences are grouped and representative sequences are selected from these groups. A new sequence is compared with all clusters and it is assigned to most similar one. Representatives of the most similar cluster can be used in several real world cases. They can be used for predicting and prefetching the next page user will visit or for helping the navigation of user in the website. They can also be used to improve the structure of website for easier navigation. In this study the effect of time spent on each web page during the session is analyzed.M.S. - Master of Scienc

Histopathological Evaluation of the Effects with Low-Intensity Pulsed Ultrasound to Allograft Osteointegration on Massive Fresh Frozen Femur Allograft Applied Rabbits.

TEZ10678Tez (Uzmanlık) -- Çukurova Üniversitesi, Adana, 2014.Kaynakça (s. 45-51) var.viii, 52 s. : res. (bzs. rnk.), tablo ; 29 cm.Amaç: Taze donmuş masif femur allogrefti uygulanmış tavşan modeli üzerinde düşük yoğunluklu kesikli ultrasonun (DYKU) allogreft osteointegrasyonu üzerine etkilerini histolojik ve radyolojik olarak göstermeyi amaçladık. Gereç ve Yöntem: Çalışmamızda 2750-3250 gr ağırlığında yetişkin Yeni Zellanda cinsi toplam 24 adet tavşan kullanıldı. 8’er tavşanlık 3 grup oluşturuldu. Birinci grup femur allogrefti kaynağı olan tavşan grubu iken ikinci grup DYKU uygulanacak olan çalışma grubu, 3. grup ise kontrol grubu olarak planlandı. Birinci gruptaki 8 adet tavşanın her iki ekstremitesinden toplam 16 adet femur grefti alındı. Alınan femur greftleri steril paketlerde -80 derece sıcaklıkta 4 hafta saklandı. 4 hafta sonunda allogreftler, çalışma ve kontrol grubundaki tavşanların femurlarında oluşturulan yaklaşık 15 mm’lik defektler yerine yerleştirildi ve 2 adet kirshner teli ile intramedüller olarak tespit edildi. Çalışma grubuna, 8 hafta boyunca, haftada 6 gün, günlük 20 dakika 1,5 mhz sinüs dalgalı, 1 khz frekans aralığında, yoğunluğu 30 mW/cm2 (Exogen®, Smith&Nephew, Memphis, ABD) uygulandı. 8 hafta sonunda çalışma ve kontrol grubundaki tavşanlar sakrifiye edildi ve femurları eksize edildi. Alınan femurlar histolojik ve radyolojik olarak incelendi. Histolojik incelemede, Santoni ve ark. ile Huo ve ark.’nın tarifledikleri skorlama yöntemi kombine edilerek kullanıldı. Radyolojik incelemede ise Taira ve arkadaşlarının skorlamasından faydalanıldı. İstatistiksel önem düzeyi 0,05 alındı. Bulgular: Histolojik incelemede, çalışma grubunda kortikal köprüleme, kallus boyutu ve kallus tipi açısından, kontrol grubuna göre istatistiksel olarak anlamlı farklılıklar elde edildi (p0,05). Radyolojik incelemede, çalışma grubunda, kontrol grubuna göre istatiksel olarak anlamlı farklılıklar saptandı (p 0.05). Radiological examination of the study group, showed statistically significant difference compared to control group (p <0.05) Conclusion: In the literatüre, activity on fracture healing of LIPUS has been shown in many studies. The number of studies of effectiveness for allograft (especially fresh frozen allografts that used in solid tumors surgery frequently) is less in the literature. In our study concluded that LIPUS increase the osteointegration of fresh-frozen massive allograft on rabbit femur model. With LIPUS that may be obtained successful for clinical use to patient who applied massive fresh-frozen allograft results delayed union or nonunion. However, to find the effectiveness of allograft osteointegration and this effect provides by which the mechanism that is needed more in vitro and animal studies

Additional file 1: of Assessment of transfer methods for comparative genomics of regulatory networks in bacteria

Distribution of TF-binding sites in the compiled catalog by originating database. (DOCX 11 kb

Additional file 3: of Assessment of transfer methods for comparative genomics of regulatory networks in bacteria

Generation of noisy transfers and controls. (PPT 136 kb