Chi-square-based scoring function for categorization of MEDLINE citations

Objectives: Text categorization has been used in biomedical informatics for identifying documents containing relevant topics of interest. We developed a simple method that uses a chi-square-based scoring function to determine the likelihood of MEDLINE citations containing genetic relevant topic. Methods: Our procedure requires construction of a genetic and a nongenetic domain document corpus. We used MeSH descriptors assigned to MEDLINE citations for this categorization task. We compared frequencies of MeSH descriptors between two corpora applying chi-square test. A MeSH descriptor was considered to be a positive indicator if its relative observed frequency in the genetic domain corpus was greater than its relative observed frequency in the nongenetic domain corpus. The output of the proposed method is a list of scores for all the citations, with the highest score given to those citations containing MeSH descriptors typical for the genetic domain. Results: Validation was done on a set of 734 manually annotated MEDLINE citations. It achieved predictive accuracy of 0.87 with 0.69 recall and 0.64 precision. We evaluated the method by comparing it to three machine learning algorithms (support vector machines, decision trees, na\"ive Bayes). Although the differences were not statistically significantly different, results showed that our chi-square scoring performs as good as compared machine learning algorithms. Conclusions: We suggest that the chi-square scoring is an effective solution to help categorize MEDLINE citations. The algorithm is implemented in the BITOLA literature-based discovery support system as a preprocessor for gene symbol disambiguation process.Comment: 34 pages, 2 figure

Clinical genetics and breast cancer

Geneti čki čimbenici već su dugo poznati kao važni rizični čimbenici kod raka dojke. Procjenjuje se da je oko 5 do 10 % slučajeva raka dojke posljedica monogenske geneti čke predispozicije. U medicinskoj obradi raka dojke važno je prepoznati one žene i obitelji kod kojih postoji velika mogućnost monogenske geneti čke predispozicije, kako bi im se omogućila primjerena genetička i klinička obrada. Naime, osobama s visokim rizikom može se ponuditi mogućnost otkrivanja genetičkim testom (dijagnosti čko ili presimptomatsko testiranje) i drugačiju razinu medicinske obrade u smislu rane prevencije i liječenja u usporedbi s općom populacijom.It is known that geneti c factors play an important role as risk factors in breast cancer. 5 to 10% of breast cancer is of monogenetic predispositi on. In the process of clinical evaluati on of pati ents with breast cancer it is very importnat to identify those pati ents with high probability of having cancer predisposing mutati ons and to provide them relevant and professional genetic and clinical management. This can lead to the identification of genetic etiology of breast cancer and allow earlier and more efficient prevention, screening and treatment of breast cancer

THE ROLE OF MICROBIOTA IN DEPRESSION - A BRIEF REVIEW

The microbiota-gut-brain axis is a bidirectional homeostatic route of communication between both of the organs direct via receptors of the CNS or via epigenetic mechanisms of divers metabolites e.g. SCFA, GAB

CLINICAL EXOME SEQUENCING IN DEMENTIAS: A PRELIMINARY STUDY

Background: Dementias are clinically and genetically heterogeneous group of neurodegenerative disorders. Often, dementias with genetic etiology are clinically indistinguishable from non-genetic ones. The aim of this retrospective study was to evaluate the yield of clinical exome sequencing in dementias, potentially associated with monogenic genetic predisposition. Subjects and methods: For this purpose 20 consecutive patients younger than 65 years were studied in the period from January 2014 to December 2017; 14 with the diagnosis of Frontotemporal dementia (FTD), 3 with early-onset Alzheimer disease (EOAD) and 3 with unspecified dementia. In addition to clinical exome sequencing including 57 genes associated with dementia, C9orf72 hexanucleotide expansion as tested in all patients. Results: We found genetic etiology in 6 patients: 2 mutations in the PSEN1 gene (p.Pro264Ser and p.Phe105Cys) in the EOAD patients, C9orf72 expansion and MAPT (c.1920+16C>T), mutation in the FTD group of patients as well as MAPT (c.1920+16C>T) mutation and likely pathogenic mutation in the TYROBP mutation (p.Asp32Asn) in patients with unspecified diagnosis. Conclusions: Our preliminary results imply significant diagnostic yield in identifying rare genetic causes of dementia, combining comprehensive clinical exome sequencing and targeted C9orf72 expansion testing

DNA testing in medicine

Brz razvoj genetike kao znanosti pridonio je boljem poznavanju molekularnih osnova bolesti, što je omogućilo razvoj pouzdane dijagnostičke metode – DNA testiranja. Cilj je DNA testiranja otkriti genetičku promjenu – mutaciju, koja je po molekularnoj logici bolesti metoda izbora u dijagnostici genetički uvjetovanih bolesti. Nužno je poznavati kompleksnosti upotrebe genetičkog testiranja, jer je osim racionalne indikacije važan i izbor odgovarajućeg testa, pravilna interpretacija rezultata, poznavanje njegovih ograničenja, specifičnosti te poznavanje etičkih, legalnih i socijalnih implikacija. Genetičko savjetovanje stoga treba biti integralni dio svakog procesa genetičkog testiranja.The rapid development of genetics as a science has brought with it an increasing knowledge of the molecular bases of diseases, which in turn has allowed the development of better and more accurate diagnostic test – DNA analysis. The goal of DNA analysis in medicine is to detect genetic changes (mutations) which, by molecular logic, is the most accurate way to confirm the presence of genetic disease. It is important to understand the complexity of the use of genetic testing as there are (besides the importance of indicating the appropriate analysis, correct interpretation of any results, an understanding of the limits of testing and its specifity) many legal and ethical implications connected with genetic testing. It therefore follows that genetic counseling should be an integral part of the process of genetic testing

Direct-to-consumer genetic testing in Slovenia: availability, ethical dilemmas and legislation

Introduction: Over the last few years, many private companies are advertising direct-to-consumer genetic testing (DTC GT), mostly with no or only minor clinical utility and validity of tests and without genetic counselling. International professional community does not approve provision of DTC GT and situation in some EU countries has been analysed already. The aim of our study was to analyse current situation in the field of DTC GT in Slovenia and related legal and ethical issues. Materials and methods: Information was retrieved through internet search, performed independently by two authors, structured according to individual private company and the types of offered genetic testing. Results: Five private companies and three Health Insurance Companies offer DTC GT and it is provided without genetic counselling. Available tests include testing for breast cancer, tests with other health-related information (complex diseases, drug responses) and other tests (nutrigenetic, ancestry, paternity). National legislation is currently being developed and Council of Experts in Medical Genetics has issued an opinion about Genetic Testing and Commercialization of Genetic Tests in Slovenia. Conclusions: Despite the fact that Slovenia has signed the Additional protocol to the convention on human rights and biomedicine, concerning genetic testing for health purposes, DTC GT in Slovenia is present and against all international recommendations. There is lack of or no medical supervision, clinical validity and utility of tests and inappropriate genetic testing of minors is available. There is urgent need for regulation of ethical, legal, and social aspects. National legislation on DTC GT is being prepared

C.35delG/ GJB2 and del(GJB6-D13S1830) mutations in Croatians with prelingual non-syndromic hearing impairment

BACKGROUND: C.35delG/GJB2 mutation is the most frequent genetic cause of deafness in Caucasians. Another frequent mutation in some Caucasian populations is del(GJB6-D13S1830). Both GJB2 and GJB6 genes belong to the same DFNB1 locus and when the two mutations are found in combination in a hearing-impaired person, a digenic pattern of inheritance is suggested. METHODS: We examined 63 Croatian subjects (25 familial and 38 sporadic cases) with prelingual non-syndromic hearing impairment by polymerase chain reaction for the presence of the c.35delG/GJB2 and the del(GJB6-D13S1830) mutations. RESULTS: Of the 63 unrelated hearing-impaired subjects, the mutation c.35delG/GJB2 was found in 21 subjects (33.3%). In 5 of them the mutation was found in the heterozygous state, all of them being compound heterozygotes, as sequencing revealed a second mutation within the coding region of the gene in 3 subjects, and a splice site mutation in 2 subjects. The del(GJB6-D13S1830) mutation was not found in the investigated hearing-impaired Croatian subjects. CONCLUSION: Our results contribute to the knowledge of geographic distribution and population genetics of the GJB2 and GJB6 mutations in the Europeans