Inference from binary gene expression data

Microarrays provide a practical method for measuring the mRNA abundances of thousands of genes in a single experiment. Analysing such large dimensional data is a challenge which attracts researchers from many different fields and machine learning is one of them. However, the biological properties of mRNA such as its low stability, measurements being taken from a population of cells rather than from a single cell, etc. should make researchers sceptical about the high numerical precision reported and thus the reproducibility of these measurements. In this study we explore data representation at lower numerical precision, down to binary (retaining only the information whether a gene is expressed or not), thereby improving the quality of inferences drawn from microarray studies. With binary representation, we propose a solution to reduce the effect of algorithmic choice in the pre-processing stages.First we compare the information loss if researchers made the inferences from quantized transcriptome data rather than the continuous values. Classification, clustering, periodicity detection and analysis of developmental time series data are considered here. Our results showed that there is not much information loss with binary data. Then, by focusing on the two most widely used inference tools, classification and clustering, we show that inferences drawn from transcriptome data can actually be improved with a metric suitable for binary data. This is explained with the uncertainties of the probe level data. We also show that binary transcriptome data can be used in cross-platform studies and when used with Tanimoto kernel, this increase the performance of inferences when compared to individual datasets. In the last part of this work we show that binary transcriptome data reduces the effect of algorithm choice for pre-processing raw data. While there are many different algorithms for pre-processing stages there are few guidelines for the users as to which one to choose. In many studies it has been shown that the choice of algorithms has significant impact on the overall results of microarray studies. Here we show in classification, that if transcriptome data is binarized after pre-processed with any combination of algorithms it has the effect of reducing the variability of the results and increasing the performance of the classifier simultaneously

Evaluation of clinical, diagnostic and treatment aspects in hydatid disease: analysis of an 8-year experience

Background & Objective: Echinococcosis is still a common health problem. The aim of this study was to discuss our 8-year data in terms of diagnosis, treatment and follow-up of cystic Echinococcosis.Methods: A total of 178 patients who had hydatid cyst were analyzed retrospectively from the hospital records. The diagnosis of hydatid cyst was based on clinical-serological and radiological findings. Treatment response was evaluated with clinical, radiological and serological findings.Results: A total of 178 medical records were evaluated; the male:female ratio was 0.73 and mean age 44.6±16.9 years. The most common symptom was abdominal pain (94, 52.8%). The mean cyst size was 9.5±3.9 cm. Eosinophilia was significantly higher in patients with complicated cyst (35.3%) (p=0.002). The average duration of hospitalization in surgical patients was shorter than non-surgical patients (p=0.026). There was no significant correlation between the preference of scolicidal agent (hypertonic saline, H2O2, povidone iodine) and recurrence in patients who underwent surgery (p>0.05). There was no significant difference between the patients who underwent radical and conservative surgery in terms of complication and recurrence (p=0.077, p=0.557). No significant difference was found between percutaneous and surgical treatment in terms of complication and recurrence (p=0.264, p=0.276).Conclusion: Even though considerable progress has been made, uncertainties remain in the diagnosis and treatment of Echinococcosis. Hence, standardized diagnostic and treatment procedures should be established with well-designed studies.Keywords: Echinococcosis, hydatid cyst, diagnosis, treatment

Evaluation of clinical, diagnostic and treatment aspects in hydatid disease: analysis of an 8-year experience

Background & Objective: Echinococcosis is still a common health problem. The aim of this study was to discuss our 8-year data in terms of diagnosis, treatment and follow-up of cystic Echinococcosis. Methods: A total of 178 patients who had hydatid cyst were analyzed retrospectively from the hospital records. The diagnosis of hydatid cyst was based on clinical-serological and radiological findings. Treatment response was evaluated with clinical, radiological and serological findings. Results: A total of 178 medical records were evaluated; the male:female ratio was 0.73 and mean age 44.6\ub116.9 years. The most common symptom was abdominal pain (94, 52.8%). The mean cyst size was 9.5\ub13.9 cm. Eosinophilia was significantly higher in patients with complicated cyst (35.3%) (p=0.002). The average duration of hospitalization in surgical patients was shorter than non-surgical patients (p=0.026). There was no significant correlation between the preference of scolicidal agent (hypertonic saline, H2O2, povidone iodine) and recurrence in patients who underwent surgery (p>0.05). There was no significant difference between the patients who underwent radical and conservative surgery in terms of complication and recurrence (p=0.077, p=0.557). No significant difference was found between percutaneous and surgical treatment in terms of complication and recurrence (p=0.264, p=0.276). Conclusion: Even though considerable progress has been made, uncertainties remain in the diagnosis and treatment of Echinococcosis. Hence, standardized diagnostic and treatment procedures should be established with well-designed studies

Nieinwazyjny pomiar ilości tkanki tłuszczowej trzewnej metodą ultrasonograficzną — potencjalne zastosowanie w ocenie zaawansowania subklinicznej miażdżycy u mężczyzn z niedoczynnością przysadki i niedoborem hormonu wzrostu

Introduction: Growth hormone (GH) deficiency, either isolated or combined with other pituitary hormone deficiencies, is associated with increased mortality and abnormal body composition, particularly visceral adiposity. We aimed to investigate the effects of GH deficiency with or without sex steroid deficiencies on ultrasonographic visceral fat (VF) and cardiovascular risk markers in patients with hypopituitarism on conventional hormone replacement therapy.Material and methods: Forty hypopituitarism patients (24 women, 16 men; mean age 48 ± 16.1 years) with GH deficiency and 15 age- and sex-matched healthy controls were included in this cross-sectional study. The patients were stable on conventional hormone replacement but they were not on GH therapy. Patients who had sex steroid replacement were classified as Group 1 (n = 19), and patients who did not use sex steroids were classified as Group 2 (n = 21). Anthropometric measurements were performed. VF in three regions, subcutaneous fat, and carotid intima-media thickness (CIMT) were measured. VF volume was calculated by using a formula.Results: Visceral fat volume and mean CIMT were significantly higher in patients than healthy controls (p = 0.001 and 0.019 respectively). Homocysteine and hs-CRP were higher in patients (p < 0.05). In males, VF volume and VF thickness measured between abdominal muscle and splenic vein were significantly correlated with CIMT (r = 0.54, p = 0.047 and r = 0.66, p = 0.010 respectively). Furthermore, there was a strong positive correlation between VF thickness in pararenal region and homocysteine (r = 0.74, p = 0.001) in males.Conclusions: VF volume evaluated by ultrasound can be accepted as a cause of subclinical atherosclerosis in GH deficient hypopituitary patients, particularly males.Wstęp: Niedobór hormonu wzrostu (GH, growth hormone) może występować jako zaburzenie izolowane lub współistnieć z niedoborami innych hormonów przysadki. Wszyscy pacjenci z niedoborem GH są jednak obarczeni większym ryzykiem zgonu i mają nieprawidłowy skład tkanek ciała, z tendencją do otyłości brzusznej. Celem pracy była ocena zależności pomiędzy niedoborem GH, niezależnie od ewentualnego współistnienia niedoborów hormonów płciowych a grubością tkanki tłuszczowej trzewnej (VF, visceral fat) mierzoną metodą ultrasonograficzną oraz czynnikami ryzyka sercowo-naczyniowego u pacjentów z niedoczynnością przysadki, leczonych konwencjonalnymi preparatami hormonalnymi.Materiał i metody: Badanie miało charakter przekrojowy i zakwalifikowano do niego 40 pacjentów z niedoczynnością przysadki i niedoborem GH, w tym 24 kobiety, 16 mężczyzn; średni wiek badanych wynosił 48 ± 16,1 lat. Do badania włączono też 15 osób w grupie kontrolnej, dobranych pod względem płci i wieku do osób z grupy badanej. Pacjenci w grupie badanej leczeni byli konwencjonalnie preparatami hormonalnymi, ale nie otrzymywali hormonu wzrostu. Pacjenci leczeni hormonami płciowymi zostali włączeni do grupy 1 (n = 19), a pacjenci nie otrzymujący takich preparatów do grupy 2 (n = 21). U wszystkich wykonano badania antropometryczne. Wykonywano pomiar grubości VF w trzech miejscach, badano grubość podskórnej tkanki tłuszczowej oraz grubość warstwy wewnętrznej i środkowej ściany tętnicy szyjnej (CIMT, carotid intima-media thickness). Objętość VF wyliczano według wzoru.Wyniki: U pacjentów w grupie badanej stwierdzono znamiennie większą objętość trzewnej tkanki tłuszczowej i średnią wartość CIMT w porównaniu z osobami zdrowymi (odpowiednio p = 0,001 i p = 0,019). Stężenie homocysteiny i hs-CRP były również większe w grupie badanej (p < 0,05). U mężczyzn stwierdzono istotną korelację pomiędzy objętością VF i grubością VF mierzoną pomiędzy mięśniami brzucha a żyłą śledzionową a wartością CIMT (odpowiednio r = 0,54 i p = 0,047 oraz r = 0,66 i p = 0,010). Ponadto, u mężczyzn stwierdzono wyraźną zależność pomiędzy grubością VF w okolicy nerek a stężeniem homocysteiny (r = 0,74 i p = 0,001).Wnioski: Objętość VF mierzona ultrasonograficznie może być wykładnikiem subklinicznie toczącej się miażdżycy u pacjentów z niedoborem hormonu wzrostu na skutek niedoczynności przysadki, w szczególności u mężczyzn

Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans.

Several strands of evidence question the dogma that human mitochondrial DNA (mtDNA) is inherited exclusively down the maternal line, most recently in three families where several individuals harbored a 'heteroplasmic haplotype' consistent with biparental transmission. Here we report a similar genetic signature in 7 of 11,035 trios, with allelic fractions of 5-25%, implying biparental inheritance of mtDNA in 0.06% of offspring. However, analysing the nuclear whole genome sequence, we observe likely large rare or unique nuclear-mitochondrial DNA segments (mega-NUMTs) transmitted from the father in all 7 families. Independently detecting mega-NUMTs in 0.13% of fathers, we see autosomal transmission of the haplotype. Finally, we show the haplotype allele fraction can be explained by complex concatenated mtDNA-derived sequences rearranged within the nuclear genome. We conclude that rare cryptic mega-NUMTs can resemble paternally mtDNA heteroplasmy, but find no evidence of paternal transmission of mtDNA in humans

Qualidade dos frutos de variedades de videira do Banco Ativo de Germoplasma da Embrapa Semiárido.

O objetivo deste trabalho foi caracterizar a qualidade de uvas tintas para consumo in natura e para processamento, conservadas no Banco Ativo de Germoplasma (BAG) de videira da Embrapa Semiárido

Author Correction: Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses

Abstract: IL-6 excess is central to the pathogenesis of multiple inflammatory conditions and this is targeted in clinical practice by immunotherapy that blocks the IL-6 receptor encoded by IL6R. We describe two patients with homozygous mutations in IL6R who presented with recurrent infections, abnormal acute phase responses, elevated IgE, eczema, and eosinophilia. This study identifies a novel primary immunodeficiency, clarifying the contribution of IL-6 to the phenotype of patients with mutations in IL6ST, STAT3 and ZNF341, genes encoding different components of the IL-6 signalling pathway, and alerts us to the potential toxicity of drugs targeting the IL-6R.J.E.D.T. is supported by the MRC (RG95376 and MR/L006197/1). KB is supported by the European Research Council (ERC StG 310857) and the Austrian Science Fund (P29951-B30). This work is supported, in part, by the intramural research program of the NIAID, NIH. A.J.T. is supported by the Wellcome Trust (104807/Z/14/Z) and the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. KGCS is supported by the Medical Research Council (program grant MR/L019027) and is a Wellcome Investigator. M.G. and S.T. are supported in part by Cancer Research UK. RCA and MT are supported by a DOC fellowship of the Austrian Academy of Sciences. This research was made possible through access to the data and findings generated by two pilot studies for the 100,000 Genomes Project. The enrolment for one pilot study was coordinated by the NIHR BioResource (preprint from doi: https://doi.org/10.1101/507244) and the other by Genomics England Limited (GEL), a wholly owned company of the Department of Health in the UK. Over 90% of participants in the pilot studies have been enrolled in the NIHR BioResource. These pilot studies were mainly funded by grants from the National Institute for Health Research (NIHR) in England to the University of Cambridge and GEL, respectively. Additional funding was provided by the BHF, MRC, NHS England, the Wellcome Trust, amongst many other funders. The pilot studies use data provided by patients and their close relatives and collected by the NHS and other healthcare providers as part of their care and support. We thank all volunteers for their participation, and also gratefully acknowledge NIHR Biomedical Research Centres, NIHR BioResource Centres, NHS Trust Hospitals, NHS Blood and Transplant and staff for their contribution. ST is on the scientific advisory board for Ipsen, and is a consultant for Kallyope Inc. The authors declare no competing financial interests

A gain-of-function variant in <i>DIAPH1 </i>causes dominant macrothrombocytopenia and hearing loss

Macrothrombocytopenia (MTP) is a heterogeneous group of disorders characterized by enlarged and reduced numbers of circulating platelets, sometimes resulting in abnormal bleeding. In most MTP, this phenotype arises because of altered regulation of platelet formation from megakaryocytes (MK). We report the identification of DIAPH1, which encodes the Rho-effector diaphanous-related formin 1 (DIAPH1), as a candidate gene for MTP using exome sequencing, ontological phenotyping and similarity regression. We describe two unrelated pedigrees with MTP and sensorineural hearing loss that segregate with a DIAPH1 p.R1213* variant predicting partial truncation of the DIAPH1 diaphanous autoregulatory domain. The R1213* variant was associated with reduced proplatelet formation from cultured MKs, cell clustering and abnormal cortical filamentous actin. Similarly, in platelets there was increased filamentous actin and stable microtubules, indicating constitutive activation of DIAPH1. Over-expression of DIAPH1 R1213* in cells reproduced the cytoskeletal alterations found in platelets. Our description of a novel disorder of platelet formation and hearing loss extends the repertoire of DIAPH1-related disease and provides new insights into the autoregulation of DIAPH1 activity