Statistical methods for the integrative analysis of single-cell multi-omics data

Single-cell profiling techniques have provided an unprecedented opportunity to study cellular heterogeneity at the molecular level. This represents a remarkable advance over traditional bulk sequencing methods, particularly to study lineage diversification and cell fate commitment events in heterogeneous biological processes. While the large majority of single-cell studies are focused on quantifying RNA expression, transcriptomic readouts provide only a single dimension of cellular heterogeneity. Recently, technological advances have enabled multiple biological layers to be probed in parallel one cell at a time, unveiling a powerful approach for investigating multiple dimensions of cellular heterogeneity. However, the increasing availability of multi-modal data sets needs to be accompanied by the development of suitable integrative strategies to fully exploit the data generated. In this thesis I worked in collaboration with different research groups to introduce innovative experimental and computational strategies for the integrative study of multi-omics at single-cell resolution. The first contribution is the development of scNMT-seq, a protocol for the simultaneous profiling of RNA expression, DNA methylation and chromatin accessibility in single cells. I demonstrate how this assay provides a powerful approach for investigating regulatory relationships between the epigenome and the transcriptome within individual cells. The second contribution is Multi-Omics Factor Analysis (MOFA), a statistical framework for the unsupervised integration of multi-omics data sets. MOFA is a Bayesian latent variable model that can be viewed as a statistically rigorous generalization of Principal Component Analysis to multi-omics data. The method provides a principled approach to retrieve, in an unsupervised manner, the underlying sources of sample heterogeneity while at the same time disentangling which axes of heterogeneity are shared across multiple modalities and which are specific to individual data modalities. The third contribution is the generation of a comprehensive molecular roadmap of mouse gastrulation at single-cell resolution. We employed scNMT-seq to simultaneously profile RNA expression, DNA methylation and chromatin accessibility for hundreds of cells, spanning multiple time points from the exit from pluripotency to primary germ layer specification. Using MOFA, and other tools, I performed an integrative analysis of the multi-modal measurements, revealing novel insights into the role of the epigenome in regulating this key developmental process. The fourth contribution is an extended formulation of the MOFA model tailored to the analysis of large-scale single-cell data with complex experimental designs. I extended the model to incorporate a flexible regularisation that enables the joint analysis of multiple omics as well as multiple sample groups (batches and/or experimental conditions). In addition, I implemented a GPU-accelerated stochastic variational inference framework, thus enabling the scalable analysis of potentially millions of samples

Elementos de cambio y de continuidad en la militancia de ERC (1993-2004)

En este artículo, se analiza la base humana del partido político catalán que se presenta como independentista: Esquerra Republicana de Catalunya. Para ello, se estudian los datos sociológicos de los asistentes a cuatro congresos nacionales del partido celebrados a lo largo del período 1993-2004: los de 1993, 1998, 2001 y 2004. La finalidad es plantear la profundidad de los vínculos -y el sentido de los mismos- entre base humana, oferta político- ideológica del partido y actuación pública en sus opciones de alianzas parlamentarias. A partir de los datos obtenidos, se traza el perfil del militante de ERC y se observan las pautas de cambio y de continuidad que ha habido a lo largo de estas casi dos décadas.This article analyses the sociological profile the membership of the Catalan political party that presents itself as pro-independence, Esquerra Republicana de Catalunya. In order to do so, it offers data on the sociological profile of those attending four national party conferences over the 1993-2004 period: the conferences of 1993, 1998, 2001 and 2004. The overall aim is to analyse the strength and direction of the relationship between the party membership, the political and ideological position of the party, and the latter's parliamentary strategies. Based on such data, the article profiles the ERC membership and observes the trends of change and continuity over the period studied

GiAnt: stereoscopic-compliant multi-scale navigation in VEs

International audienceNavigation in multi-scale virtual environments (MSVE) requires the adjustment of the navigation parameters to ensure optimal navigation experiences at each level of scale. In particular, in immersive stereoscopic systems, e.g. when performing zoom-in and zoom-out operations, the navigation speed and the stereoscopic rendering parameters have to be adjusted accordingly. Although this adjustment can be done manually by the user, it can be complex, tedious and strongly depends on the virtual environment. In this work we propose a new multi-scale navigation technique named GiAnt (GIant/ANT) which automatically and seamlessly adjusts the navigation speed and the scale factor of the virtual environment based on the user's perceived navigation speed. The adjustment ensures an almost-constant perceived navigation speed while avoiding diplopia effects or diminished depth perception due to improper stereoscopic rendering configurations. The results from the conducted user evaluation shows that GiAnt is an efficient multi-scale navigation which minimizes the changes of the scale factor of the virtual environment compared to state-of-the-art multi-scale navigation techniques

VIRTUAL REALITY & SPORT

This applied session deals with the design of immersive environments for human motion performance analysis. In a first part of the session, a theoretical presentation describes the aims and scopes of such type of experiments. In a second part of the session, a review of the available immersive systems will be exposed. Finally, a practical framework will be designed in real-time with the attendees: a low-cost immersive environment based on a Microsoft Kinect, a Razer Hydra and an Oculus Rift Head Mounted Display device. We will develop an experiment to analyse perception-action coupling in soccer with simulated virtual opponents enabling to analyse the decision-making of a real goalkeeper

Eliminació de microcontaminants orgànics d’aigües residuals mitjançant processos de sorció

El projecte que es presenta en aquest document, té com a finalitat l’estudi dels processos de sorció per a la separació sòlid – líquid, aplicats a l’eliminació de microcontaminants orgànics procedents d’efluents industrials, basant-se principalment en l’estudi detallat de la modelització d’aquests processos. Per a poder realitzar una bona modelització, és bàsic estudiar tant la branca de l’equilibri com la de cinètica. Dins la part d’equilibri es realitzen les isotermes d’adsorció, les quals mostren la distribució de l’adsorbat entre la fase adsorbida i la solució a l’equilibri a una temperatura determinada. Segons quines són les hipòtesis inicials i les simplificacions realitzades, es poden trobar diferents expressions per al càlcul de les isotermes. Les més utilitzades, i conseqüentment les que s’han aplicat per als càlculs d’aquest projecte, són les isotermes de Langmuir, Freundlich , Temkin i Redlich – Peterson, havent-se creat una macro en entorn Excel per al càlcul còmode i eficaç de les tres primeres. D’altra banda, també és necessari disposar d’un model matemàtic que descrigui la cinètica del procés. La cinètica dels processos de sorció pot arribar a ser molt complexa en funció del model utilitzat, i tot i haver-ne estudiat diversos de diferent grau de complexitat, han estat els models HPDM i SPM els escollits per a calcular els dos paràmetres cinètics bàsics: el coeficient de difusió efectiu i el coeficient de transferència de matèria. Per altra banda, s’ha volgut aprofundir més en aquest camp, i s’ha realitzat un programa amb Maple utilitzant el model HSDM, el qual és molt més complex però a la vegada més fiable. Aquest programa informàtic s’ha creat amb l’objectiu de poder disposar d’una eina que permeti simular el comportament d’un sistema sense necessitat d’haver de realitzar un treball experimental previ. Per últim s’ha realitzat un disseny molt bàsic de l’equipament necessari per a realitzar el tractament d’aigües mitjançant processos de sorció a escala de laboratori. Els resultats obtinguts mostren que les dues isotermes que més s’ajusten a les dades experimentals són la de Langmuir i la de Temkin. Per altra banda, dins la part cinètica, s’ha pogut comprovar que l’etapa controlant de la velocitat depèn tant de l’adsorbat com de l’adsorbent que composin el sistema. Cal tenir en compte que aquestes dades són una primera aproximació a la definició del dimensionament del tractament a escala pilot com a fase prèvia a la seva implementació a escala real

Friction surfaces: scaled ray-casting manipulation for interacting with 2D GUIs

The accommodation of conventional 2D GUIs with Virtual Environments (VEs) can greatly enhance the possibilities of many VE applications. In this paper we present a variation of the well-known ray-casting technique for fast and accurate selection of 2D widgets over a virtual window immersed into a 3D world. The main idea is to provide a new interaction mode where hand rotations are scaled down so that the ray is constrained to intersect the active virtual window. This is accomplished by changing the control-display ratio between the orientation of the user’s hand and the ray used for selection. Our technique uses a curved representation of the ray providing visual feedback of the orientation of both the input device and the selection ray. The users’ feeling is that they control a flexible ray that gets curved as it moves over a virtual friction surface defined by the 2D window. We have implemented this technique and evaluated its effectiveness in terms of accuracy and performance. Our experiments on a four-sided CAVE indicate that the proposed technique can increase the speed and accuracy of component selection in 2D GUIs immersed into 3D worlds.Peer ReviewedPostprint (author’s final draft

Estudi històric-artístic i seguiment executiu de la rehabilitació d'un edifici de tres plantes entremitgeres al call jueu de Girona

L’objectiu d’aquest treball és principalment plasmar i estudiar amb un minuciós seguiment gran part de l’execució dels treballs de rehabilitació d’un edifici entremitgeres de tres plantes situat al Call jueu de la ciutat de Girona. D’altre banda, també es farà el seguiment de la reconstrucció d’un volum de nova planta a un dels patis interiors, on ja hi havia existit un de vell ja derruït