A QPTAS for Gapless MEC

We consider the problem Minimum Error Correction (MEC). A MEC instance is an n x m matrix M with entries from {0,1,-}. Feasible solutions are composed of two binary m-bit strings, together with an assignment of each row of M to one of the two strings. The objective is to minimize the number of mismatches (errors) where the row has a value that differs from the assigned solution string. The symbol "-" is a wildcard that matches both 0 and 1. A MEC instance is gapless, if in each row of M all binary entries are consecutive. Gapless-MEC is a relevant problem in computational biology, and it is closely related to segmentation problems that were introduced by {[}Kleinberg-Papadimitriou-Raghavan STOC\u2798{]} in the context of data mining. Without restrictions, it is known to be UG-hard to compute an O(1)-approximate solution to MEC. For both MEC and Gapless-MEC, the best polynomial time approximation algorithm has a logarithmic performance guarantee. We partially settle the approximation status of Gapless-MEC by providing a quasi-polynomial time approximation scheme (QPTAS). Additionally, for the relevant case where the binary part of a row is not contained in the binary part of another row, we provide a polynomial time approximation scheme (PTAS)

Computational haplotyping : theory and practice

Genomics has paved a new way to comprehend life and its evolution, and also to investigate causes of diseases and their treatment. One of the important problems in genomic analyses is haplotype assembly. Constructing complete and accurate haplotypes plays an essential role in understanding population genetics and how species evolve. In this thesis, we focus on computational approaches to haplotype assembly from third generation sequencing technologies. This involves huge amounts of sequencing data, and such data contain errors due to the single molecule sequencing protocols employed. Taking advantage of combinatorial formulations helps to correct for these errors to solve the haplotyping problem. Various computational techniques such as dynamic programming, parameterized algorithms, and graph algorithms are used to solve this problem. This thesis presents several contributions concerning the area of haplotyping. First, a novel algorithm based on dynamic programming is proposed to provide approximation guarantees for phasing a single individual. Second, an integrative approach is introduced to combining multiple sequencing datasets to generating complete and accurate haplotypes. The effectiveness of this integrative approach is demonstrated on a real human genome. Third, we provide a novel efficient approach to phasing pedigrees and demonstrate its advantages in comparison to phasing a single individual. Fourth, we present a generalized graph-based framework for performing haplotype-aware de novo assembly. Specifically, this generalized framework consists of a hybrid pipeline for generating accurate and complete haplotypes from data stemming from multiple sequencing technologies, one that provides accurate reads and other that provides long reads.Die Genomik hat neue Wege eröffnet, die es ermöglichen, die Evolution lebendiger Organismen zu verstehen, sowie die Ursachen zahlreicher Krankheiten zu erforschen und neue Therapien zu entwickeln. Ein wichtiges Problem ist die Assemblierung der Haplotypen eines Individuums. Diese Rekonstruktion von Haplotypen spielt eine zentrale Rolle für das Verständnis der Populationsgenetik und der Evolution einer Spezies. In der vorliegenden Arbeit werden Algorithmen zur Assemblierung von Haplotypen vorgestellt, die auf Sequenzierdaten der dritten Generation basieren. Dies erfordert große Mengen an Daten, welche wiederum Fehler enthalten, die die zugrunde liegenden Sequenzierprotokolle hervorbringen. Durch kombinatorische Formulierungen des Problems ist die Rekonstruktion von Haplotypen dennoch möglich, da Fehler erfolgreich korrigiert werden können. Verschiedene informatische Methoden, wie dynamische Programmierung, parametrisierte Algorithmen und Graph Algorithmen können verwendet werden, um dieses Problem zu lösen. Die vorliegende Arbeit stellt mehrere Lösungsansätze für die Rekonstruktion von Haplotypen vor. Als erstes wird ein neuartiger Algorithmus vorgestellt, der basierend auf dem Prinzip der dynamischen Programmierung Approximationsgarantien für das Haplotyping eines einzelnen Individuums liefert. Als zweites wird ein integrativer Ansatz präsentiert, um mehrere Sequenzierdatensätze zu kombinieren und somit akkurate Haplotypen zu generieren. Die Effektivität dieser Methode wird auf einem echten, menschlichen Datensatz demonstriert. Als drittes wird ein neuer, effzienter Algorithmus beschrieben, um Haplotypen verwandter Individuen simultan zu konstruieren und die Vorteile gegenüber der Betrachtung einzelner Individuen aufgezeigt. Als viertes präsentieren wir eine Graph-basierte Methode um mittels Haplotypinformation de-novo Assemblierung durchzuführen. Dieser Methode kombiniert Daten stammend von verschiedenen Sequenziertechnologien, welche entweder genaue oder aber lange Sequenzierreads liefern

Comparative analysis of fibreoptic bronchoscope aided cytohistological techniques in diagnosis of benign and malignant lesions of lung

Background: Morbidity and mortality from chronic lung diseases are increasing worldwide. A combination of various cytological and histopathological techniques are required for the high diagnostic accuracy. This study aims to evaluate and compare diagnostic accuracy of fiberoptic bronchoscope aided cytohistological techniques such as BAL (bronchoalveolar lavage), TBNA (Transbronchoscopic needle aspiration) and FB (forceps biopsy) in diseases of lung. Method: A prospective study conducted on 100 patients with symptoms and signs of various respiratory diseases who underwent fibreoptic bronchoscopy. Diagnostic accuracy of various samples alone and in combination were analysed. Results: Sensitivity of BAL-24%, TBNA 64% and FB 66%. Addition of BAL to FB increased the sensitivity to 69%. Addition of BAL to TBNA increased the sensitivity to 70%. Sensitivity of cytological methods (FB and TBNA) 90%. Addition of both BAL and TBNA to FB increased overall senstivity to 93%. FB the most specific amongst the three techniques with specificity of 94% followed by TBNA (59.4%) and BAL (50%). Conclusions: There are variable results regarding diagnostic yields and utilities of various fibre-optic bronchoscope aided cytohistological techniques but there combination adds the yields. Thus a combination of various cytohistological samples should be taken in a patient undergoing fiberoptic bronchoscopic examination to increase the diagnostic yield, to cut short the diagnostic time and early start of treatment

Occurrence and risk factors of Vitamin D deficiency in Indian children living with HIV – A case–control study

Background: Vitamin D deficiency (VDD) is highly prevalent in healthy individuals. Studies suggest that Vitamin D plays an important role in immune system. Objective: The objective of this study was to assess the frequency of VDD in Indian children living with HIV (CLHIV) and to find out the risk factors associated with it. Materials and Methods: It was a cross-sectional comparative study conducted in a tertiary care teaching hospital of North India. A total of 52 CLHIV were enrolled consecutively from the pediatric HIV center and an equal number of age- and sex-matched controls were enrolled from the pediatric outpatient department. Serum Vitamin D levels of cases and controls were assessed and compared. Various risk factors, both classical (age, sex, sunlight exposure, average dietary intake of calcium, and Vitamin D) and disease related (WHO and immunological stage, duration, and regimen of treatment), were evaluated for VDD in CLHIV. Results: The prevalence of VDD in cases and controls was 69.23% and 19.23%, respectively (p<0.001). The mean serum Vitamin D level of the cases (18.24±11.2 ng/dL) was significantly lower than that of controls (31.58±17.31 ng/dL) (p<0.001). The risk factor that predicted the occurrence VDD in CLHIV was a poor intake of Vitamin D. Conclusion: CLHIV are more prone to VDD; hence, there is a need to regularly evaluate, supplement, and monitor for Vitamin D status in these children

Adrenal ganglioneuroma; a rare neurogenic tumor in a 25-year-old female

Ganglioneuromas (GNs) are rare benign tumors originating from the neural crest tissue. They are characteristically located in the posterior mediastinum and retroperitoneum; and are rarely found in the adrenal gland. GNs are usually hormonally inactive, and most of the cases are detected incidentally. We report a case of 25-year-old female who presented with pain abdomen in the right upper quadrant. Imaging studies showed a large well defined hypodense lesion with calcification measuring 14.5×11.5×11cm in the region of right adrenal gland and a possibility of adrenocortical carcinoma was suggested. The patient underwent right adrenalectomy and histopathological examination revealed ganglioneuroma. This report emphasizes that GN can be misdiagnosed preoperatively as the presenting symptoms are nonspecific and imaging characteristics are variable. Histopathological examination is the mainstay of diagnosis

Pulmonary blastomycosis on autopsy: a rare case report

A case of pulmonary blastomycosis on autopsy in a middle aged male from rural background is presented herewith. Blastomycosis is a pyogranulomatous disease caused by the dimorphic fungus blastomyces dermatitidis. Blastomycosis is endemic in regions of North America that border the Great Lakes. It is one of the great mimickers in medicine. Pulmonary blastomycosis has a broad range of clinical presentations, varying from completely asymptomatic pulmonary infiltrates to diffuse and massive parenchymal involvement that can lead to Acute Respiratory Distress Syndrome (ARDS). Human infection occurs when soil containing microfoci of mycelia is distributed and airborne conidia are inhaled. If natural defences in the alveoli fail to contain the infection, lymphohematogenous dissemination ensues. Diagnosis is based on culture and direct visualization of round, multinucleated yeast forms that produce daughter cells from a single broad- based bud. Most of the cases of blastomycosis reported in India are imported from the endemic areas of the World except a few authochthonous cases in North India

Isolated tuberculous epididymo-orchitis masquerading as testicular tumor: a diagnostic dilemma

Isolated tuberculous epididymo-orchitis is rare and may present with clinical and radiological features similar to those of testicular tumor. It is thus a diagnostic and therapeutic challenge. A 40 yrs old male presented with left sided mass in scrotum for past 6 months, which was clinically and radiologically diagnosed as testicular tumor with hydrocele. FNAC was attempted twice but was inconclusive. Left sided orchiectomy was done. However, the histopathological findings of testicular mass revealed features consistent with tuberculous epididymo- orchitis (TEO). This case emphasizes that patient may present with isolated TEO, which is considered an unusual presentation of tuberculosis and can masquerade as testicular tumor clinically and radiologically. But in countries where prevalence of tuberculosis is high, tuberculous orchitis must be considered in the differential diagnosis of testicular swellings

Inferior turbinate osteoma: a case report

Osteoma is the most common benign tumor of the paranasal sinuses. Turbinate osteomas are very rare and only five middle turbinate, two inferior turbinate and one superior turbinate osteoma cases have been reported. We present a rare case of osteoma of the left inferior turbinate in a patient presented with unilateral nasal obstruction that was removed endoscopically and conduct a literature review on turbinate osteomas arising from different turbinates

A histopathological analysis of prevalence of various heart diseases: an autopsy study

Background: Objective was to study the histopathological spectrum of heart diseases in autopsy specimens, that play a major role as cause of death.Methods: During the period from October 2015 to October 2017. Total 170 medicolegal autopsies were received during this period. Out of 170, specimens of heart were 150. Nine specimens were autolyzed. So, 141 specimen of heart were included in the study. Gross and microscopic findings on H and E stained sections were studied.Results: out of 141 cases, 78 cases showed atherosclerosis, 20 cases showed features of myocardial infarction, myocardial hypertrophy was found in 10 cases, 5 cases revealed myocarditis, pericarditis in 4 cases and one case each of infective endocarditis and aortic stenosis. In 22 cases, there was no identifiable cause of death even after complete gross and microscopic autopsy was performed.Conclusions: Myocardial infarction due to atherosclerosis is probably the commonest finding in death cases subjected to medicolegal autopsies