Multi-task Deep Neural Networks in Automated Protein Function Prediction

In recent years, deep learning algorithms have outperformed the state-of-the art methods in several areas thanks to the efficient methods for training and for preventing overfitting, advancement in computer hardware, the availability of vast amount data. The high performance of multi-task deep neural networks in drug discovery has attracted the attention to deep learning algorithms in bioinformatics area. Here, we proposed a hierarchical multi-task deep neural network architecture based on Gene Ontology (GO) terms as a solution to protein function prediction problem and investigated various aspects of the proposed architecture by performing several experiments. First, we showed that there is a positive correlation between performance of the system and the size of training datasets. Second, we investigated whether the level of GO terms on GO hierarchy related to their performance. We showed that there is no relation between the depth of GO terms on GO hierarchy and their performance. In addition, we included all annotations to the training of a set of GO terms to investigate whether including noisy data to the training datasets change the performance of the system. The results showed that including less reliable annotations in training of deep neural networks increased the performance of the low performed GO terms, significantly. We evaluated the performance of the system using hierarchical evaluation method. Mathews correlation coefficient was calculated as 0.75, 0.49 and 0.63 for molecular function, biological process and cellular component categories, respectively. We showed that deep learning algorithms have a great potential in protein function prediction area. We plan to further improve the DEEPred by including other types of annotations from various biological data sources. We plan to construct DEEPred as an open access online tool.Comment: 19 pages, 4 figures, 4 table

Rekreativni ribolov na turskim obalama srednjeg i istočnog Crnog mora: biološki, socijalni i ekonomski aspekti

This study investigated biological, social and mainly economic dimensions of recreational fishing (RF) in 8 coastal Middle and Eastern Black Sea provinces of Turkey. In all provinces, a total number of 874 shore-based recreational fishers were interviewed via on-site face-to-face interviews during the fishing activity or at access points being monthly from January to December in 2015. Market value with RF index of added value approaches were used to calculate economic gains and losses from RF. The consistency was observed with the high education levels, high expense and high market value for fishers in the Middle Black Sea provinces; Kastamonu, Samsun, Sinop and Ordu. In all provinces, the harvesting costs stayed far below the average market prices of target species. Also, positive values of RF index were observed in all provinces. The species catch composition in Western and Eastern provinces did not show great differences. Furthermore, even if the habitat type along the Black Sea coast of Turkey did not show great variations, in the Western provinces some certain species including T. trachurus, S. sarda, B. belone, P. saltatrix, M. cephalus were caught in higher amounts. To summarize, RF along the Black Sea coasts of Turkey is an industry creating high economic returns by expenditures, jobs, catch value and further increased indirect economic impact in services sector.U ovoj studiji se iznose istraživanja biološke, društvene i ekonomske dimenzije rekreacijskog ribolova (RF) u 8 srednje obalnih i istočnih pokrajina Crnog mora u Turskoj. U svim pokrajinama ukupno je 874 obalnih rekreativnih ribara anketirano izravnim intervjuima (razgovorom licem u lice), te tijekom ribolova ili pri pristupnim točkama mjesečno od siječnja do prosinca 2015. godine. Tržišna vrijednost prema indeksu rekreativnog ribolova i dodane vrijednosti korištena je za izračun ekonomskih dobitaka i gubitaka kod rekreativnog ribolova. Konzistencija je promatrana s obzirom na visoki stupanj obrazovanja, visoke troškove i visokom tržišnom vrijednošću za ribare u slijedećim pokrajinama srednjeg Crnog mora: Kastamonu, Samsun, Sinop i Ordu. U svim pokrajinama troškovi ribolova bili su daleko ispod prosječnih tržišnih cijena ciljanih vrsta. Također, u svim pokrajinama zabilježene su pozitivne vrijednosti indeksa rekreativnog ribolova. Sastav ulova u zapadnim i istočnim pokrajinama nije pokazao velike razlike. Nadalje, iako stanišne vrste duž crnomorske obale Turske nisu pokazivale velike varijacije, u zapadnim provincijama neke određene vrste, uključujući Trachurus trachurus, Sarda sarda, Belone belone, Pomatomus saltatrix, Mugil cephalus bile su uhvaćene u većim količinama. Ukratko, rekreativni ribolov na crnomorskim obalama Turske je industrija koja stvara visoki ekonomski povrat izdataka u vidu radnih mjesta, ulovne vrijednosti i daljnjeg povećanja neizravnog ekonomskog utjecaja u sektoru usluga

Mentoring relationships as an enhancer of mentees’ success

A review of the recent studies about tertiary education student development reveals that when mentors do not practice effective relationships in mentoring programs regardless of how well designed the mentoring programs are, the goals will not be achieved. Even though many studies have been done, the role of mentoring relationships as a vital predicting variable is largely ignored in the tertiary education mentoring research literature. Hence, the current study is done to investigate the effect of mentoring relationships on mentees’ success. A cross-sectional method is used to collect survey questionnaires from undergraduate students in teaching-based universities in Sarawak. The SmartPLS is utilized to assess the quality of the study instrument and test the research hypotheses. The findings of the SmartPLS path model analysis reveal that implementation of comfortable communication and sufficient support by mentors in structured and unstructured mentoring activities has been an important antecedent of mentees’ career and leadership development. Thus, this finding may be used as significant guidelines by practitioners to understand diverse paradigms of mentoring relationship construct and planning collaborative and developmental mentoring programs to prepare mentees to become potential leaders in the 21st century of global market challenges and difficulties

DEEPred: Automated Protein Function Prediction with Multi-task Feed-forward Deep Neural Networks

Automated protein function prediction is critical for the annotation of uncharacterized protein sequences, where accurate prediction methods are still required. Recently, deep learning based methods have outperformed conventional algorithms in computer vision and natural language processing due to the prevention of overfitting and efficient training. Here, we propose DEEPred, a hierarchical stack of multi-task feed-forward deep neural networks, as a solution to Gene Ontology (GO) based protein function prediction. DEEPred was optimized through rigorous hyper-parameter tests, and benchmarked using three types of protein descriptors, training datasets with varying sizes and GO terms form different levels. Furthermore, in order to explore how training with larger but potentially noisy data would change the performance, electronically made GO annotations were also included in the training process. The overall predictive performance of DEEPred was assessed using CAFA2 and CAFA3 challenge datasets, in comparison with the state-of-the-art protein function prediction methods. Finally, we evaluated selected novel annotations produced by DEEPred with a literature-based case study considering the 'biofilm formation process' in Pseudomonas aeruginosa. This study reports that deep learning algorithms have significant potential in protein function prediction; particularly when the source data is large. The neural network architecture of DEEPred can also be applied to the prediction of the other types of ontological associations. The source code and all datasets used in this study are available at: https://github.com/cansyl/DEEPred

Aflatoksikoza u rotvajlera nakon uzimanja pljesnive hrane: kliničkopatološki nalazi i učinkovita terapija tetrasulfatom.

The purpose of this study was to describe the clinical, hematologic, gross, histopathologic and toxicologic findings and to report effective therapy application for aflatoxicosis in dogs, ascribed to the ingestion of moldy wet bread contaminated with aflatoxin. A prospective case series of 10 client-owned dogs from the same household developed toxicological signs after eating moldy bread treated with water that had been stored for an undetermined period, fully covered with a grey-green mold. All dogs exhibited vomiting followed by excessive salivation and hyperaesthesia. Among the surviving dogs (n = 7), three of them presented with diarrhea, depression, abdominal pain and two others showed icterus. One of the dead dogs was found on the initial referral. Two others were dead following initial diagnosis and prior to therapy application. The most common gross findings in the dogs were generalized icterus, mucosal or submucosal edema and petechial, to ecchymotic hemorrhages in the organs. Histopathological findings included focal necrotic areas extending from the periacinar to centroacinar regions in the liver, biliary hyperplasia, cholestasis and multifocal hemorrhages in the kidneys and lungs. Due to the sudden onset of clinical signs, the lack of exposure to other toxins, and the confirmed evidence of ingestion of moldy bread, the results of analysis of liver samples and the histopathological signs, the definitive diagnosis was mycotoxicosis. Therapeutic applications included tetrasulphate (an antidote) given orally, and supportive treatment with balanced electrolyte solutions, antiemetics and H2 receptor antagonist. All treated dogs (7/7) made a full recovery over 18-24 hours. The results of the present study reported here describe the clinicopathological features of aflatoxicosis in Rottweilers, suggesting that the use of tetrasulphate solution as an inexpensive and available therapy may have helped the survival of the dogs and might reverse the adverse health effects of mycotoxins.Svrha je ovog rada iznijeti kliničke, hematološke, patoanatomske, patohistološke i toksikološke nalaze te izvijestiti o uspješnom liječenju pasa koji su jeli pljesnivu i vlažnu hranu što je sadržavala aflatoksin. U 10 pasa jednog vlasnika primijećeni su znakovi otrovanja nakon što su jeli pljesniv kruh namočen u vodu koji je prethodno bio čuvan neodređeno vrijeme, a u potpunosti je bio prekriven sivo-zelenom plijesni. Svi su psi povraćali uz obilno slinjenje i hiperesteziju. Od sedam preživjelih pasa, tri su imala proljev, bili su potišteni te su pokazivali bol u trbuhu, a dva su imala i žuticu. Jedan od uginulih pasa na početku je upućivao na toksikozu. Dva su uginula nakon postavljene dijagnoze, a prije početka liječenja. Patoanatomski je ustanovljena generalizirana žutica, edem sluznice ili submukoze te petehijalna do ekhimotična krvarenja po organima. Patohistološki su ustanovljena nekrotična žarišna područja pružajući se od periacinarnih do centroacinarnih područja u jetri, zatim bilijarna hiperplazija, kolestaza i multifokalna krvarenja po bubrezima i plućima. Na osnovi nagle pojave kliničkih znakova, nedostatka dokaza izloženosti drugim toksinima, potvrđenog dokaza uzimanja pljesnivog kruha, rezultata analize uzoraka jetre i patohistoloških nalaza postavljena je konačna dijagnoza mikotoksikoze. Za liječenje je peroralno bio primijenjen tetrasulfat(antidot) i uravnotežena otopina elektrolita, zatim antiemetici i antagonisti H 2 receptora. Svi liječeni psi (7/7) u potpunosti su se oporavili za 18 do 24 sata. Prikazani rezultati opisuju kliničke i patološke značajke aflatoksikoze u rotvajlera i upućuju na zaključak da se ona može liječiti otopinom tetrasulfata kao jeftinim i pristupačnim lijekom koji može pomoći u preživljavanju pasa te smanjiti štetne učinke mikotoksina na zdravlj

An unusual finding after adrenal surgery: a case series of adrenal schwannomas

Adrenal schwannomas are rare benign tumors with no specific imaging and laboratory findings to diagnose preoperatively. Due to the limited number of cases in the literature, clinical, imaging, and pathological findings are presented in this study. Case 1 is a 61-year-old woman patient who has a 31-mm mass in the right adrenal gland. This mass was nonfunctional; in imaging studies, this mass had a cystic necrotic component, and high 18-fluorodeoxyglucose (FDG) uptake was seen. There was no metaiodobenzylguanidine (MIBG) uptake. Laparoscopic transabdominal right adrenalectomy was performed, and the pathology result was consistent with adrenal schwannomas. Case 2 is a 63-year-old man patient who presented with a 38-mm mass in the left adrenal gland. This mass was nonfunctional and similar to that in Case 1; this mass had a cystic component. Laparoscopic transabdominal left adrenalectomy was performed. The diagnosis of adrenal schwannoma with degeneration was revealed. Case 3 was a 72-year-old woman patient admitted to the hospital for a 125-mm left adrenal mass. Similar to Case 1, this mass also had a cystic necrotic component in imaging studies. High FDG uptake was seen, and the patient underwent conventional adrenalectomy due to the suspicion of malignancy. After pathological evaluation, a diagnosis of adrenal schwannoma was made. A main diagnostic challenge in adrenal schwannomas is the preoperative diagnosis. These masses have no pathognomonic finding or specific hormonal function. Imaging findings of these masses may increase the suspicion of malignancy, which may affect decisions for surgery and the surgical technique

High prevalence of spondyloarthritis and ankylosing spondylitis among familial Mediterranean fever patients and their first-degree relatives: further evidence for the connection

INTRODUCTION: Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by recurrent attacks of fever and serositis. Limited data suggest that the prevalence of sacroiliitis is increased in patients with FMF. In our present study, we assessed the prevalence of spondyloarthritis (SpA), including ankylosing spondylitis (AS), among a cohort of FMF patients and their unaffected first-degree relatives (FDRs). METHODS: The current study cohort comprised a consecutive group of 201 unrelated patients with FMF and 319 FDRs (≥ 16 years old). These subjects were examined according to a standard protocol. RESULTS: A total of 157 FMF patients (78.1%) and 233 (73%) unaffected FDRs reported back pain. Fifteen FMF patients (7.5%) and nine unaffected FDRs fulfilled the modified New York (mNY) criteria for AS. One additional FDR with AS was identified after review of the medical records. None of the FMF patients with AS was HLA-B27 positive. The allele frequency of M694V among the FMF patients with radiographic sacroiliitis was significantly higher in comparison with those without sacroiliitis (OR 4.3). When compared with the general population, the risk ratios for SpA and AS among the FDRs of our FMF patients were 3.3 (95% CI; 2.0 to 5.5) and for AS 2.9 (95% CI; 1.3 to 6.4), respectively. CONCLUSIONS: Our study suggests that a) factors other than HLA-B27 play a role in the association of FMF and SpA/AS; b) MEFV gene variations may be one of the geographic/region-specific potential pathogenetic links between these two disorders in the Turkish population

The expressions of HSP70 and αB-crystallin in myocarditis associated with foot-and-mouth disease virus in lambs

This study describes the expression of heat shock protein70 (HSP70) and alpha-basic-crystallin (α-BC) and their association with apoptosis and some related adaptor proteins in the pathogenesis of foot-and-mouth disease virus (FMDV)-induced myocarditis in lambs. HSP70 was generally overexpressed in the myocardial tissues and inflammatory cells of FMDV-induced myocarditis with differential accumulation and localization in same hearts when compared to non-foot-and-mouth disease control hearts. α-BC immunolabeling showed coarse aggregations in the Z line of the cardiomyocytes in FMDV-infected hearts in contrast to control hearts. Overall, the results of this study show that the anti-apoptotic proteins, HSP70 and α-BC, were overexpressed with increased apoptosis in FMDV-infected heart tissues. Both proteins failed to protect the cardiomyocytes from apoptosis as defense mechanisms to the FMDV during the infection, suggesting that the virus is able to increase apoptosis via both downregulation and/or upregulation of these anti-apoptotic proteins

Crowdsourced mapping of unexplored target space of kinase inhibitors

Despite decades of intensive search for compounds that modulate the activity of particular protein targets, a large proportion of the human kinome remains as yet undrugged. Effective approaches are therefore required to map the massive space of unexplored compound-kinase interactions for novel and potent activities. Here, we carry out a crowdsourced benchmarking of predictive algorithms for kinase inhibitor potencies across multiple kinase families tested on unpublished bioactivity data. We find the top-performing predictions are based on various models, including kernel learning, gradient boosting and deep learning, and their ensemble leads to a predictive accuracy exceeding that of single-dose kinase activity assays. We design experiments based on the model predictions and identify unexpected activities even for under-studied kinases, thereby accelerating experimental mapping efforts. The open-source prediction algorithms together with the bioactivities between 95 compounds and 295 kinases provide a resource for benchmarking prediction algorithms and for extending the druggable kinome. The IDG-DREAM Challenge carried out crowdsourced benchmarking of predictive algorithms for kinase inhibitor activities on unpublished data. This study provides a resource to compare emerging algorithms and prioritize new kinase activities to accelerate drug discovery and repurposing efforts

Laboratuvardan Kliniğe Transplantasyon Pratiği

Transplantasyon; Temel Tıbbi Bilimler, Moleküler Tıp, Genetik ve İmmünolojiden klinik uygulamalardan destek alan multidisipliner bir tıp dalıdır. Temel bilimlerdeki başarılı çalışmaların kliniğe uygulanması, klinikte karşılaşılan sorunların da, oluşturulan deneysel hayvan modellerinde irdelenmesi, elde edilen bilgilerin klinik uygulamalara aktarılması; diğer deyişle tecrübelerin “Translational” özellikli olması günümüz transplantasyon çalışmalarında bir gerekliliktir. İmmün sistemin bileşenlerinin ve reaksiyonlarının iyi bilinmesi, hücreler arası ilişkilerde greftin reddi ya da kabul edilmesinin şartlarını doğru anlamak ve uygun laboratuvar yöntemleri ile klinik durumun aydınlatılması transplantasyonda stratejik önemdedir. Bu nedenle, klinik transplantasyon çalışmaları yapanlar temel bilimler bilgileri ile de donanımlı olmalıdırlar. Multidisipliner bir dal olma bilinci ile yapılan klinik transplantasyon çalışmalarında başarı yakalanmaktadır. Laboratuvardan Kliniğe Transplantasyon kitabımızda tüm yönleri ile transplantasyonun organizmaya etkileri ve bunların klinik sonuçlarını, çalışmalarımızın ışığında sunmayı ve tartışmayı hedefledik. Editör: Prof.Dr. Mesut İzzet TİTİZ Yardımcı Editör: Doç.Dr. Pınar AT