La thématique des maladies infectieuses représente un réel enjeu politique, économique et de santé publique. Les objectifs de mes travaux de thèse étaient de développer des approches protéomiques pour identifier, détecter, caractériser et/ou quantifier des protéines et de les appliquer à l’étude de maladies infectieuses pour lesquelles des données de protéomique pourraient ouvrir à de nouvelles approches thérapeutiques et/ou diagnostiques. Les stratégies d’identification et de détection des protéines développées pour l’étude de la maladie de Lyme ont permis de prouver la faisabilité du diagnostic par spectrométrie de masse et de proposer des protéines candidates-vaccin. Les stratégies de quantification mises en place pour l’étude de la toxoplasmose ont permis d’identifier et de quantifier un complexe protéique clef. Les stratégies de caractérisation du N-terminome pour l’étude du paludisme ont permis d’apporter des preuves expérimentales des processus de maturation et d’adressage des protéines. / Infectious diseases represent a real challenge in terms of politic, economic and public health. The purposes of my thesis works were to develop proteomic approaches able to identify, to detect, to characterize and/or to quantify proteins and to apply these approaches to the study of infectious diseases for which proteomic data cou Id open to new therapeutic and/or diagnostic strategies. Identification and specific detection strategies developed in the study of Lyme's disease allowed to prove the feasibility of diagnosis by mass spectrometry and to propose new vaccine-candidate proteins. Quantification strategies developed in the study of toxoplasmosis allowed us to identify and to quantify a key protein complex of the parasite. N-terminome characterization strategy developed in the study of malaria allowed us to bring experimental proofs of proteins processing and trafficking.

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of Non-Hodgkin´s Lymphoma (NHL). The standard treatment for DLBCL is R-CHOP chemoimmunotherapy (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone). About one -third of patients have refractory disease or the lymphoma relapses. Prognosis after relapse of refractory disease is poor. Fitter and younger patients are recommended new intensive salvage chemotherapy followed by autologous stem cell transplantation. Central nervous system (CNS) relapse is the most feared complication with dismal prognosis in DLBCL. High dose methotrexate intravenously administered concurrently with R-CHOP treatment has shown to be most promising to prevent CNS relapses. Primary CNS lymphoma (PCNSL) is a rare aggressive lymphoma limited to the CNS and eyes. PCNSL is a chemo-and radiosensitive disease, but long-term response is rare since the blood brain barrier (BBB) limits access of many drugs to the CNS. BBB disruption (BBBD) is a treatment modality where the BBB is opened by hypertonic mannitol infusion. Administration of chemotherapeutics will achieve over ten-fold concentrations in the CNS and eradicate microscopic disease involvement. This study retrospectively analyses patients who treated as first line with Bonn/Bonn-like treatment (study I), with BBBD treatment followed by high-dose treatment/autologous stem cell transplantation (HDT/ASCT) in first- or second-line (study II) or those treated with primary R-CHOP or its derivatives with or without concurrent CNS-targeted treatment (study III). HD-MTX-based multichemotherapy is an effective induction treatment in CNS lymphoma, but long-lasting responses are rare. BBBD-treatment is well-tolerated and a promising method to attain high drug concentrations in the CNS to eradicate microscopic disease involvement in first- and second-line. CNS-prophylaxis with HD-MTX prevents CNS events in high risk DLBCL. PCNSL is agressive disease despite excellent primary response with HD-MTX based multichemotherapy. BBBD-treatment is a promising method to eradicate microscopic disease in the CNS and achieve a long-term response and cure rate. Fatal CNS relapses can be avoided using CNS-targeted treatment. / Tiivistelmä Diffuusi suurisoluinen B-solulymfooma (DLBCL) on yleisin non-Hodgkin lymfooma (NHL), jonka standardihoitona toimii R-CHOP (rituksimabi, syklofosfamidi, vinkristiini, doksorubisiini, prednisoloni). Noin kolmasosalla potilaista tautii etenee hoidosta huolimatta tai uusii hoidon päätyttyä. Relapoituneen tai refraktaarin taudin ennuste on huono. Hyväkuntoisilla ja nuoremmilla potilailla pyritään etenemään uuteen induktiohoitoon ja korkea-annoshoitoon autologisen kantasolusiirteen turvin. Keskushermostouusiutuma on huonoennusteisin DLBCL:n komplikaatio. Suuriannosmetotreksaattihoito liitettynä R-CHOP-hoitoon estää keskushermostouusiutumia. Primaari aivolymfooma (PCNSL) on harvinainen keskushermoston ja silmien alueelle rajautuva lymfooma. PCNSL on herkkä sytostaatti-ja sädehoidolle, mutta pitkäkestoisia vasteita nähdään harvoin. Veriaivoeste estää useimpien tehokkaiden sytostaattien pääsyn keskushermostoon. Veriaivoesteen aukaisuhoidossa veriaivoeste avataan hypertonisella mannitoli-infuusiolla. Toimenpiteen jälkeisellä sytostaatti-infuusiolla saavutetaan kymmenkertaiset lääkeainepitoisuudet keskushermostossa ja voidaan hoitaa mikroskooppista veriaivoesteen takana sijaitsevaa tautia. Väitöskirjatyön tutkimukset ovat retrospektiivisiä. Ensimmäisessä osatyössä analysoitiin PCNSL potilaat, jotka saivat ensilinjassa Bonnin tai Bonnin kaltaista hoitoa. Toisessa osatyössä potilaat hoidettiin joko ensi- tai toisessa linjassa BBBD-hoidolla, päättyen konsolidaatiohoitona annettavaan korkea-annoshoitoon autologisen kantasolusiirteen turvin. Kolmannessa osatyössä analysoitiin suuren aivouusiutumariskin potilaita, joko yhdessä tai ilman keskushermostoon suunnattua hoitoa samanaikaisesti R-CHOP-hoidon kanssa. Suuriannosmetotreksaatti-pohjainen yhdistelmäsolunsalpaajahoito on tehokas induktiohoito aivolymfoomassa pitkäkestoisten vasteiden ollessa harvinaisia. BBBD-hoito on hyvin siedetty ja lupaava hoitomuoto, jolla keskushermostossa voidaan saavuttaa suuret lääkeainepitoisuudet, jotka riittävät hoitamaan mikroskooppisen taudin sekä ensi että toisessa linjassa. Keskushermostoprofylaksia suuriannosmetotreksaatilla estää keskushermosto-uusiutumia suuren riskin DLBCL-potilailla. PCNSL on agressiivinen tauti huolimatta erinomaisista metotreksaattipohjaisilla hoidoilla saavutetuista ensilinjan vasteista. BBBD-hoito on lupaava keino eradikoida mikroskooppinen tauti keskushermostosta ja saavuttaa pitkäaikaisia hoitovasteita, sekä pysyvä paraneminen aivolymfoomassa. Suuriannosmetotreksaattia sisältävällä sytostaattihoidolla voidaan estää fataaleja aivorelapseja DLBCL:ssä.

The field of early detection and intervention of hearing loss in neonates and infants has been marked by a growing international body of research investigating hearing screening programmes, protocols and outcomes of early detection for hearing loss. In South Africa, screening for neonates and infants in general and particularly for hearing loss is not common practice and is not meeting the needs of the South African population, with very few infants identified with hearing loss early in life. The Year 2002 Hearing Screening Position Statement recommends an intermediate step toward universal screening in the form of Targeted Newborn Hearing Screening (TNHS) as an option for developing countries with limited resources. The Neonatal Intensive Care Unit (NICU) provides a starting point for TNHS because it encompasses a number of risk factors for hearing loss. A combined descriptive and exploratory research methodology was followed to provide a comprehensive perspective on longitudinal hearing screening for NICU neonates and infants at a provincial hospital in South Africa. The quantitative methods included a structured interview to compile risk factor information. Immittance measurements used included acoustic reflex measurements, 226 Hz and 1000 Hz tympanometry. Automated Otoacoustic Emission (AOAE) as well as Automated Auditory Brainstem Response (AABR) screening was conducted. Routine follow-up visits at three month intervals were booked if a subject passed the screen and a follow-up screening for further testing was booked if a subject referred the screening. A total of 49 neonates and infants as well as mothers were enrolled in the first year and followed up for the second year of data collection period. The results indicated that the NICU had potential as platform for TNHS in South Africa. The high incidence of risk factors reported is more when compared with developed countries and highlights the importance of hearing screening in the at risk population for a developing country. The results confirmed reports that 226 Hz probe tone tympanometry produces erroneous responses in young infants. A high correspondence between high frequency tympanometry and AOAE results was found and underlines the need for differential diagnosis to accurately detect middle ear effusion and/or sensorineural hearing loss in neonates and infants. The unilateral AOAE refer rate (7%) was within range of the reported values for initial screening at discharge from the NICU. AABR results indicated a relatively high unilateral refer result (24%) and may be attributed to irritability and restlessness. The highest referral rates in the current study were recorded during the second and third visit and may be attributed to the presence of middle-ear pathology in older infants. The perceptions of mothers emphasized the lack of awareness regarding hearing and hearing loss in South Africa. Lack of knowledge may be a contributing actor to poor compliance with screening follow-up. Despite prevailing challenges, such as a low follow-up return rate, lack of awareness regarding the benefits of early detection of hearing loss, the effect of middle ear effusion on screening results, the cost of hearing screening and different priorities of the national healthcare system, such as Human Immunodeficiency Virus, demonstrated the NICU promise as platform for TNHS in South Africa. TNHS programmes may serve as starting point to direct universal neonatal hearing screening programmes in South Africa. / Dissertation (MCommunication Pathology)--University of Pretoria, 2008. / Speech-Language Pathology and Audiology / MComm Path / unrestricted

Brachydactyly type A1 (BDA1) is a rare autosomal dominant trait characterized by the shortening of the middle phalanges of digits 2-5 and of the proximal phalange of digit 1 in both hands and feet. Many of the brachymesophalangies including BDA1 have been associated with genetic perturbations along the BMP-SMAD signaling pathway. The goal of this thesis is to identify the molecular pathways that are associated with the BDA1 phenotype through the genetic assessment of BDA1-affected families. We identified four missense mutations that are clustered with other reported BDA1 mutations in the central region of the N-terminal signaling peptide of IHH. We also identified a missense mutation in GDF5 cosegregating with a semi-dominant form of BDA1. In two families we reported two novel BDA1-associated sequence variants in BMPR1B, the gene which codes for the receptor of GDF5. In 2002, we reported a BDA1 trait linked to chromosome 5p13.3 in a Canadian kindred (BDA1B; MIM %607004) but we did not discover a BDA1-causal variant in any of the protein coding genes within the 2.8 Mb critical region. To provide a higher sensitivity of detection, we performed a targeted enrichment of the BDA1B locus followed by high-throughput sequencing. We report the identification of a novel 9.5 Kb intergenic tandem duplication in two unrelated BDA1-affected families. In-vitro and in-vivo reporter assays demonstrated the enhancer activity of noncoding conserved sequence elements found within the microduplication. We also show an upregulation of the neighboring genes, NPR3 and PDZD2, in the patients' fibroblasts that suggests a gain-of-function through the duplication of cis-regulatory elements on dose sensitive genes. By expanding the repertoire of BDA1-causing mutations in IHH, GDF5, BMPR1B and at the BDA1B locus, we have begun to elucidate a common genetic pathway underlying phalangeal formation and elongation.

Le rhabdomyosarcome de l'adulte est une tumeur rare au pronostic. Le présent travail propose d'étudier les caractéristiques cliniques et moléculaires et la prise en charge des adolescents et adultes atteints de rhabdomyosarcome ainsi que la possibilité de combinaison de thérapie ciblées sur lignées cellulaires in vitro. Nous avons anamysé rétrospectivement 239 patients âgés de 10 ans ou plus, atteints de rhabdomyosarcome au MD Anderson Cancer Center entre 1957 et 2003 et leur statut fusionnel pour PAX-FOXO1 par hybridation in situ en fluorescence. Trois lignées cellulaire de sarcome à petites cellules ont été soumises à des combinaisons de thérapies ciblées avec analyse de la viabilité. Les patients de plus de 50 ans avaient une survie globale à 5 ans de 13 % (médiane de survi à 1.7 ans) en dépit d'une maladie localisée. Approximativement 13 % des patients métastasiques de moins de 50 ans ont eu une survie prolongée de plus de 15 ans. L'utilisation d'une stratégie thérapeutique triple, intégrant chirurgie, chimiothérapie et radiothérapie était signifcativement associée à une survie prolongée. Auniveau molécualire, la présence du transcrit de fusio PAX3/7-FOXO1 était significativement liée à un risque accru de maladie métastatique. L'étude in vitro de thérapies ciblées a permis d'identifier la combinaison du vorinostat plus le 17DMAG associée à la doxorubicine comme ayant une meilleure efficacité. La prise en charge du rhabdomyosarcome de l'adolescent et de l'adulte semble souffrir d'une approche moins agressive comparée au rhabdomyosarcome pédiatrique. De plus, des combianaisons de thérapies ciblées peuvent être intégrées aux protocoles de chimiothérapies standards. / Rhabdomyosarcoma is a rare entity adult patient with unfavourable outcome. This work describes the clinical and molecular specificities of adolescent and adult type of rhabdomyosarcoma and investigates the optimal integration of targetd therapy combinations on small cell sarcoma cell lines in vitro. We retrospectively analyzed 239 patients, 10 years of age and greater, diagonsed withrhabdomyosarcoma at MD Anderson Cancer Center from 1957 trough 2003 and their PAX-FOXO1 fusion gene status by fluorescence in situ hybridization on tissues microarray. Three samll cell sarcoma cell lines were exposed to targetd agent combinations. PAtient with metastatic rhabdomyosarcoma were found to have a 18 % survival rate at 5 years from diagnosis with an 12 %survival past 15 years. This outcome was even poorer for patients over 50 of age, even with localized disease. Younger patients were more likely to receive multidisciplinary therapy than their older counterparts. The presence of PAX-FOXO1 tranlocation was significantly associated with a higher frequency of metastatic disease. The four agents with the exception of abacavir synergized two by two with each other in vitro but the triple combinations did not perform beter than the bitherapies. The dual therapies vorinostat 5HDAC inhibitor) plus 17-DMAG (Hsp90 inhibitor) added with doxorubicin achvied better results than dual or triple therapies. Adult patient with rhabdomyosarcoma present similar molecular and clinical characteristics compared pediatric patients but outcome decrease with age partly du to a less multimodal management. Moreover targeted combinations should be integrated to chemotherapy backbone.

This master thesis deals with the problematics of marketing in education. It analyses and compares marketing tools used in education, methods of implementing marketing activities in secondary schools in Slovakia, it examines how schools percieves problem of school massification of the education. Thesis consists of two parts. In the first part are defined basic concepts and theoretical foundations related to marketing and to the issue of massification of education. The second one is a research. Methodology characterizes research methods, methods of selection and a description of respondents. This is followed by evaluation and presentation of results. The conclusion is the summary of point key elements and it describes and evaluates the obtained knowledge.

Cette thèse porte sur le développement de méthodes semi-paramétriques robustes pour l'inférence de paramètres complexes émergeant à l'interface de l'inférence causale et la biostatistique. Ses motivations sont les applications à la recherche épidémiologique et médicale à l'ère des Big Data. Nous abordons plus particulièrement deux défis statistiques pour réconcilier, dans chaque contexte, estimation adaptative et inférence statistique. Le premier défi concerne la maximisation de l'information tirée d'essais contrôlés randomisés (ECRs) grâce à la conception d'essais adaptatifs. Nous présentons un cadre théorique pour la construction et l'analyse d'ECRs groupes-séquentiels, réponses-adaptatifs et ajustés aux covariable (traduction de l'expression anglaise « group-sequential, response-adaptive, covariate-adjusted », d'où l'acronyme CARA) qui permettent le recours à des procédures adaptatives d'estimation à la fois pour la construction dynamique des schémas de randomisation et pour l'estimation du modèle de réponse conditionnelle. Ce cadre enrichit la littérature existante sur les ECRs CARA notamment parce que l'estimation des effets est garantie robuste même lorsque les modèles sur lesquels s'appuient les procédures adaptatives d'estimation sont mal spécificiés. Le second défi concerne la mise au point et l'étude asymptotique d'une procédure inférentielle semi-paramétrique avec estimation adaptative des paramètres de nuisance. A titre d'exemple, nous choisissons comme paramètre d'intérêt la différence des risques marginaux pour un traitement binaire. Nous proposons une version cross-validée du principe d'inférence par minimisation ciblée de pertes (« Cross-validated Targeted Mimum Loss Estimation » en anglais, d'où l'acronyme CV-TMLE) qui, comme son nom le suggère, marie la procédure TMLE classique et le principe de la validation croisée. L'estimateur CV-TMLE ainsi élaboré hérite de la propriété typique de double-robustesse et aussi des propriétés d'efficacité du TMLE classique. De façon remarquable, le CV-TMLE est linéairement asymptotique sous des conditions minimales, sans recourir aux conditions de type Donsker. / This dissertation focuses on developing robust semiparametric methods for complex parameters that emerge at the interface of causal inference and biostatistics, with applications to epidemiological and medical research in the era of Big Data. Specifically, we address two statistical challenges that arise in bridging the disconnect between data-adaptive estimation and statistical inference. The first challenge arises in maximizing information learned from Randomized Control Trials (RCT) through the use of adaptive trial designs. We present a framework to construct and analyze group sequential covariate-adjusted response-adaptive (CARA) RCTs that admits the use of data-adaptive approaches in constructing the randomization schemes and in estimating the conditional response model. This framework adds to the existing literature on CARA RCTs by allowing flexible options in both their design and analysis and by providing robust effect estimates even under model mis-specifications. The second challenge arises from obtaining a Central Limit Theorem when data-adaptive estimation is used to estimate the nuisance parameters. We consider as target parameter of interest the marginal risk difference of the outcome under a binary treatment, and propose a Cross-validated Targeted Minimum Loss Estimator (TMLE), which augments the classical TMLE with a sample-splitting procedure. The proposed Cross-Validated TMLE (CV-TMLE) inherits the double robustness properties and efficiency properties of the classical TMLE , and achieves asymptotic linearity at minimal conditions by avoiding the Donsker class condition.

This doctoral thesis aimed at better understanding the contribution of sleep, Targeted Memory Reactivation and transcranial Direct Current Stimulation (tDCS) on the consolidation of neutral and emotional memories. In the first part of this work, we found that REM-enriched naps and more specifically rapid eye movement density is associated with the consolidation of sad stories, suggesting a possible implication of Ponto-Geniculo-Occipital (PGO) waves in the consolidation of sad information. In addition, we observed an increase in emotional reactivity during re-exposure to the sad story following a REM-enriched nap. We postulate that REM sleep favored the consolidation of the emotionalsalience of the sad memories, leading to exacerbated emotional reactivity during re-exposure. We also investigated the impact of TMR during NREM sleep on the consolidation of neutral and negative word pairs leanred with a specific sound. We found an equal benefit of the TMR procedure on neutral and emotional material, suggesting that emotion does not modulate the selective enhancing effect of TMR during NREM sleep. In an additional study, we tested the impact of verbatim presentation of the pairs of words during NREM sleep and did not find the memory benefits of TMR. We ascribed the absence of TMR memory benefit to the detrimental effect of the auditory presntation of the second word which impaired the memory reactivation processes initiated by the presentation of the first word. Together, theseresults indicate the crucial role of a sensitive plastic time window necessary for the successful processes of memory reactivation during sleep. Finally, we evaluated how the combination of tDCS and TMR procedure during a wakeful rest consolidation interval benefits memory consolidation. We found that TMR alone led to selective memory benefits for cued word pairs. When the TMR procedure was combined with either right-anodal or left anodal tDCS, we observed a significant improved global learning, suggesting that tDCS does not potentiate but overshadows the TMRprocedure. Altogether, these studies offer new perspectives in the field of memory consolidation. More specifically, the application of an alternating current during post-learning sleep concomitantly to a TMR procedure might favor the specific brain oscillations involved in successful memory reactivation, and might enhance the associated memory gains. / Doctorat en Sciences psychologiques et de l'éducation / info:eu-repo/semantics/nonPublished

Background: “Targeted health dialogues” is a preventive method that aims to reduce the risk of cardiovascular disease and type 2 diabetes. It includes a health-survey containing physical activity (PA)-questions. Health region Skåne introduced the method 2020 and decided to add additional questions about PA and sedentary behavior (SB). With the wish to replace current validated PA-questions with new validated questions and describe SB. Aim: Analyze concurrent validity between the answers of the original PA-questions (kcal/week) in the method and new answers (activity-minutes/last 7-days) and describe SB (hours/day). Method: Quantitative cross-sectional study with non-random, appropriate selection. Participants were 40-year-old health dialogue-participants that consented to research. Data on kcal/week, activity-minutes/last 7-days, sedentary hours/day and basic characteristics were retrieved from digital health-survey. Agreement between PA-questions was analyzed by Cohen´s weighted kappa and intraclass correlation-coefficient (ICC). SB was presented with descriptive statistics and analyzed by Chi2-test, Fisher's-exact-test and independent t-test. Result: Weak agreement between the PA-questions was found (Kw=0,378; ICC=0,273). Participants born in Sweden were more sedentary than those born outside Sweden (p<0.001) and participants with high education were more sedentary compared with lower education (p=0.014). Significant associations were found between SB and BMI (p=0.028; dichotomized analysis). Sedentary participants (>9 hours/d) also had higher mean BMI compared to those who were less sedentary (29,0(SD5,7) and 26,7(SD5,2) respectively; p=0,008). Conclusion: Current PA-questions cannot be replaced in favor of new questions in their current form. Further validation studies are warranted, preferably using objective PA-measures. SB was significantly associated with country of birth, education level and BMI. / Bakgrund: Riktade hälsosamtal är en preventiv metod med syfte att minska risken för hjärt-kärlsjukdom och diabetes typ 2. Metoden innehåller frågor om fysisk aktivitet (FA). Region Skåne införde 2020 metoden och valde att lägga till ytterligare frågor om FA samt stillasittande. Önskemålet var att ersätta tidigare validerade frågor om FA med nya validerade frågor och kartlägga stillasittandet. Syfte: Att undersöka samtidig validitet mellan svaren på de ursprungliga frågorna om FA (kcal/vecka) och svaren på de nya frågorna (aktivitetsminuter/senaste 7-dagarna) samt kartlägga stillasittandet (timmar/dag). Metod: Kvantitativ tvärsnittsstudie med icke-slumpmässigt, ändamålsenligt urval. Deltagarna utgjordes av 40-åringar som haft hälsosamtal samt lämnat forskningssamtycke. Data om kcal/vecka, aktivitetsminuter/senaste 7 dagarna, stillasittande timmar/dag samt bakgrundsinformation inhämtades från den digitala hälsoenkäten. Samstämmighet mellan svaren om FA analyserades genom beräkning av Cohens viktade kappa samt intraklass-korrelationskoefficient (ICC). Stillasittande beskrevs deskriptivt och jämförelseanalyser gjordes med Chi2-test, Fishers exakta-test och oberoende t-test. Resultat: Svag samstämmighet och överensstämmelse sågs mellan FA-frågorna (Kw =0,378; ICC=0,273). Deltagare födda i Sverige var mer stillasittande jämfört med dem födda utanför Sverige (p<0.001) och deltagare med eftergymnasial utbildning var mer stillasittande jämfört med dem utan eftergymnasial utbildning (p=0,014). Signifikant samband sågs mellan stillasittande och BMI (p=0,028; dikotomiserad analys). Medelvärdet för BMI var högre i gruppen som var stillasittande >9h/dag jämfört med ≤9 h/dag (29,0(SD5,7) respektive 26,7(SD5,2); p=0,008). Slutsats: Nuvarande frågor om FA kan inte rakt av bytas ut till förmån för de nya frågorna. Ytterligare valideringsstudier, företrädesvis med objektiva FA-mått, behövs. Nivån av stillasittande hade signifikanta samband med födelseland, utbildningsnivå och BMI.

Moderní výzkum v environmentální mikrobiologii využívá k popisu mikrobiálních komunit genomická data, především sekvenaci DNA. Oblast, která zkoumá veškerý genetický materiál přítomný v environmentálním vzorku, se nazývá metagenomika. Tato doktorská práce se zabývá metagenomikou z pohledu bioinformatiky, která je nenahraditelná při výpočetním zpracování dat. V teoretické části práce jsou popsány dva základní přístupy metagenomiky, včetně jejich základních principů a slabin. První přístup, založený na cíleném sekvenování, je dobře rozpracovanou oblastí s velkou řadou bioinformatických technik. Přesto mohou být metody pro porovnávání vzorků z několika prostředí podstatně vylepšeny. Přístup představený v této práci používá unikátní transformaci dat do podoby bipartitního grafu, kde je jedna partita tvořena taxony a druhá vzorky, případně různými prostředími. Takový graf plně reflektuje kvalitativní i kvantitativní složení analyzované mikrobiální sítě. Umožňuje masivní redukci dat pro jednoduché vizualizace bez negativních vlivů na automatickou detekci komunit, která dokáže odhalit shluky podobných vzorků a jejich typických mikrobů. Druhý přístup využívá sekvenace celého metagenomu. Tato strategie je novější a příslušející bioinformatické nástroje jsou méně propracované. Hlavní výzvou přitom zůstává rychlá klasifikace sekvencí, v metagenomice označovaná jako „binning“. Metoda představená v této práci využívá přístupu zpracování genomických signálů. Tato unikátní metodologie byla navržena na základě podrobné analýzy redundance genetické informace uložené v genomických signálech. Využívá transformace znakových sekvencí do několika variant fázových signálů. Navíc umožňuje přímé zpracování dat ze sekvenace nanopórem v podobě nativních proudových signálů.