COMIT: identification of noncoding motifs under selection in coding sequences

COMIT is presented; an algorithm for detecting functional non-coding motifs in coding regions, separating nucleotide and amino acid effects

Performance of apparent diffusion coefficient values and ratios for the prediction of prostate cancer aggressiveness across different MRI acquisition settings

PURPOSE:In this study, we assessed the performance of apparent diffusion coefficient (ADC) and diffusion-weighted imaging (DWI) metrics and their ratios across different magnetic resonance imaging (MRI) acquisition settings, with or without an endorectal coil (ERC), for the evaluation of prostate cancer (PCa) aggressiveness using whole-mount specimens as a reference.METHODS:We retrospectively reviewed the data of prostate carcinoma patients with a Gleason score (GS) of 3+4 or higher who underwent prostate MRI using a 3T unit at our institution. They were divided into two groups based on the use of ERC for MRI acquisition, and patients who underwent prostate MRI with an ERC constituted the ERC (n = 55) data set, while the remaining patients accounted for the non-ERC data set (n = 41). DWI was performed with b-values of 50, 500, 1000, and 1,400 s/mm2, and ADC maps were automatically calculated. Additionally, computed DWI (cDWI) was performed with a b-value of 2000 s/mm2. Six ADC and two cDWI parameters were evaluated. In the ERC data set, receiver operating characteristic (ROC) curves were plotted for each metric to determine the best cutoff threshold values for differentiating GS 3+4 PCa from that with a higher GS. The performance of these cutoff values was assessed in non-ERC dataset. The diagnostic accuracies and area under the curves (AUCs) of the metrics were compared using Fisher’s exact test and De Long’s method, respectively.RESULTS:Among all metrics, the ADCmean-ratio yielded the highest AUC, 0.84, for differing GS 3+4 PCa from that with a higher GS. The best threshold cutoff values of ADCmean-ratio (£0.51) for discriminating GS 3+4 PCa from that with a higher GS classified 48 patients out of 55 with an accuracy of 87.27%. However, there was no significant difference between each metric in terms of accuracy and AUC (p = 0.163 and 0.214). Similarly, in the non-ERC data set, the ADCmean-ratio provided the highest diagnostic accuracy (82.92%) by classifying 34 patients out of 41. However, Fisher’s exact test yielded no significant difference between DWI and ADC metrics in terms of diagnostic accuracy in non-ERC data (p = 0.561).CONCLUSION:The mean ADC ratio of the tumor to the normal prostate showed the highest accuracy and AUC in differentiating GS 3+4 PCa and PCa with a higher GS across different MRI acquisition settings; however, the performance of different ADC and DWI metrics did not differ significantly

A Comparative Study of Multiparametric MRI Sequences in Measuring Prostate Cancer Index Lesion Volume

Objectives: To compare the effectiveness of individual multiparametric prostate MRI (mpMRI) sequences—T2W, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE)—in assessing prostate cancer (PCa) index lesion volume using whole-mount pathology as the ground-truth; to assess the impact of an endorectal coil (ERC) on the measurements. Materials and Methods: We retrospectively enrolled 72 PCa patients who underwent 3T mpMRI with (n = 39) or without (n = 33) an ERC. A pathologist drew the index lesion borders on whole-mount pathology using planimetry (whole-mountvol). A radiologist drew the borders of the index lesion on each mpMRI sequence—T2Wvol, DWIvol, ADCvol, and DCEvol. Additionally, we calculated the maximum index lesion volume for each patient (maxMRIvol). The correlation and differences between mpMRI and whole-mount pathology in measuring the index lesion volume and the impact of an ERC were investigated. Results: The median T2Wvol, DWIvol, ADCvol, DCEvol, and maxMRIvol were 0.68 cm3, 0.97 cm3, 0.98 cm3, 0.82 cm3, and 1.13 cm3. There were good positive correlations between whole-mountvol and mpMRI sequences. However, all mpMRI-derived volumes underestimated the median whole-mountvol volume of 1.97 cm3 (P ≤ 0.001), with T2Wvol having the largest volumetric underestimation while DWIvol and ADCvol having the smallest. The mean relative index lesion volume underestimations of maxMRIvol were 39.16% ± 32.58% and 7.65% ± 51.91% with and without an ERC (P = 0.002). Conclusion: T2Wvol, DWIvol, ADCvol, DCEvol, and maxMRIvol substantially underestimate PCa index lesion volume compared with whole-mount pathology, with T2Wvol having the largest volume underestimation. Additionally, using an ERC exacerbates the volume underestimation

A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans

As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major populations detected with two detection methods. This catalog enables us to systematically study mutation rates, population segregation, genomic distribution, and functional properties of MEI polymorphisms and to compare MEI to SNP variation from the same individuals. Population allele frequencies of MEI and SNPs are described, broadly, by the same neutral ancestral processes despite vastly different mutation mechanisms and rates, except in coding regions where MEI are virtually absent, presumably due to strong negative selection. A direct comparison of MEI and SNP diversity levels suggests a differential mobile element insertion rate among populations

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Methods for Inter- and Intra-Species Genomics for the Detection of Variation and Function

Thesis advisor: Gabor T. MarthThis thesis concerns itself with the development of methods for comparing genomes. Chapter 2 is a comparative genomics investigation of coding regions across multiple species. Regions of the genome coding for proteins show higher conservation than non-coding regions. Furthermore, we show that a portion of coding regions are conserved beyond the requirements of protein conservation, supporting functions such as microRNA binding and splicing enhancement, providing the non-coding functional impetus to conservation. In Chapter 3, we focus on the detection and characterization of a particular type of structural variation - mobile element insertions (MEIs). While there are many types of mobile elements in the human genome, three of these are active and cause most of the MEI variation observed in humans: ALU, L1 and SVA elements. We detect variation across 1000 Genomes Pilot populations caused by these elements, assemble ALU elements to single nucleotide resolution, and determine actively copying species of this element. We've developed a variety of algorithmic approaches to MEI detection, and present these. Chapter 4 outlines an approach to remedy reference bias via the incorporation of variation data into the reference. In particular, we construct a pan-genome reference, demonstrated concretely via resolving ALU regions, and develop new alignment software to align against this enriched reference structure.Thesis (PhD) — Boston College, 2014.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Biology

Un processus participatif : concevoir un espace public urbain pour enfants dans un bidonville

INTRODUCTION La culture urbaine est omniprésente dans les espaces publics et concerne toutes les âges de la vie, y compris les enfants. Cette recherche rend compte d’un projet d’aménagement dont l’ambition est de concevoir un espace public pour les enfants, dont ils puissent faire leur territoire. Les enfants ne peuvent pas s’approprier l’espace lorsque l’urbanisme exclut de la ville les espaces informels, ceux qu’ils peuvent modeler plus facilement en fonction de leurs besoins. Cette étude, ..

Evaluation of cutaneous anthrax cases during an outbreak in the east region of Turkey

Background/aim: Anthrax is a zoonotic infection caused by Bacillus anthracis. We aimed to retrospectively evaluate cutaneous anthrax cases that occurred during an outbreak in eastern Turkey (Hakkari-Yüksekova), where people mostly earn their living from animal husbandry. Materials and methods: Forty-six cutaneous anthrax patients that were admitted to the hospital during a very short duration of 3 months (June–August 2011) were evaluated. Results: Out of 46 patients, 27 (52%) were women and 19 (48%) were men. The mean age was 37 ± 13 years. The distribution of occupations was 1 butcher, 1 cook, 5 farmers, 27 housewives, 11 shepherds, and 1 teacher. Multiple lesions were seen in 7 patients (15%) and the rest of the patients had only 1 lesion. We observed significant clinical differences among the cases and noted which particular symptoms were associated with the various skin lesions. We treated our patients with intramuscular procaine penicillin or oral ciprofloxacin/doxycycline. Conclusion: Anthrax is an important health problem that can cause lethal outbreaks. Therefore, one should think about anthrax when faced with a patient with history of animal contact that has a painless ulcer with edema and/or vesicles, especially in endemic countries like Turkey