Inferring the immune response from repertoire sequencing

High-throughput sequencing of B- and T-cell receptors makes it possible to track immune repertoires across time, in different tissues, and in acute and chronic diseases or in healthy individuals. However, quantitative comparison between repertoires is confounded by variability in the read count of each receptor clonotype due to sampling, library preparation, and expression noise. Here, we present a general Bayesian approach to disentangle repertoire variations from these stochastic effects. Using replicate experiments, we first show how to learn the natural variability of read counts by inferring the distributions of clone sizes as well as an explicit noise model relating true frequencies of clones to their read count. We then use that null model as a baseline to infer a model of clonal expansion from two repertoire time points taken before and after an immune challenge. Applying our approach to yellow fever vaccination as a model of acute infection in humans, we identify candidate clones participating in the response

TRASPLANTE SIMULTÿNEO DE PANCREAS-RIÿÿN. CONCEPTOS ACTUALES Y EXPERIENCIA EN CLÿNICA LAS CONDES

RESUMENEl trasplante de páncreas-riñón (TPR) para pacientes portadores de diabetes mellitus tipo 1 (DM1) con insuficiencia renal crónica terminal, ha demostrado ser una terapia eficaz para alcanzar el estado de normoglicemia de manera estable, con la consecuente disminución de las complicaciones crónicas de la DM y mejoría de la expectativa y calidad de vida. Actualmente, en casos seleccionados, se ha planteado el trasplante de páncreas (TP) como una alternativa para los pacientes con diabetes mellitus tipo 2 (DM2) considerando la diferencia entre los pacientes del tipo 1 y 2. Si bien es menos frecuente en la experiencia mundial, trasplantar pacientes con DM2 demuestra cifras alentadoras y comparables con el TP en enfermos portadores de DM1. En general, pacientes que desarrollan enfermedad renal terminal secundaria a diabetes 1 o 2 que requieren insulina, no obesos, deben ser considerados para el trasplante de páncreas con riñón simultáneo o secuencial. Clínica Las Condes es la de mayor experiencia en Chile, con resultados muy comparables a centros de gran importancia a nivel internacional.ObjetivoDar a conocer la situación actual del trasplante de páncreas y sus modalidades en el mundo y mostrar la experiencia en TPR en Clínica Las Condes en la sobrevida de los pacientes, de injerto de páncreas e injerto de riñón en 10 años y sus complicaciones, además de las técnicas quirúrgicas realizadas.MétodoSe recolectó la información de 16 pacientes sometidos a trasplante páncreas-riñón en Clínica Las Condes entre 1994-2014, analizando las variables con estadística descriptiva.ResultadosDe los 16 enfermos, 9 de ellos fueron hombres, la edad promedio fue 38,7 años al momento del trasplante, el tiempo promedio de diabetes fue 23,5+/-7.3 años. Todos los injertos pancreáticos fueron anastomosados a los vasos ilíacos comunes derechos en forma término-terminal y el duodeno fue anastomosado en 8 casos a la vejiga y en los últimos 8 al íleon. La sobrevida de los pacientes a 10 años fue del 81%, del injerto de páncreas el 82% y del injerto renal el 65%. La complicación post operatoria más importante fue sepsis, causando la muerte en 2 pacientes. Y entre las complicaciones de tipo inmunológico, 8 pacientes presentaron rechazo agudo, siendo manejados con terapia esteroidal de rescate o timo globulina.SUMMARYCombined kidney pancreas trasplant (PKT) in diabetes mellitus type 1 (DM1) patients with end stage renal disease, has proven to be an effective therapy to reach normoglicemia stability, with the consequent reduction of diabetes chronic complications an improvement in life expectancy and Quality of Life. Currently in selected cases of type 2 diabetes mellitus (DM2) patients with terminal nephropathy it has been proposed pancreas transplantation (PT) as an effective alternative. The results have been comparable between DM1 and DM2 patients. Patients who develop end stage renal disease secondary to type 1 or 2 DM, insulin dependent, non obese, should be considered for PKT. Clínica Las Condes has one of the mayor experience in Chile, in PKT, with comparable results to centers of great importance of International Level.ObjectiveTo show the situation of Pancreas Transplantation and its different modalities in the world. Also to show the experience in PKT at Clinica Las Condes, in 10 years patient's survival, in pancreas and kidney graft survival and complications and the surgical techniques.MethodInformation collected from 16 patients undergoing PKT at Clinica Las Condes between 1994-2014, analyzing the variables with descriptive statistics.ResultsOf the 16 patients, 9 were men, average age 38.7 years at transplant time; the average time of diabetes was 23.5+/-7.3 years. All pancreatic grafts were term-terminal to anastomosed the right iliac common vessels and duodenum was anastomosed is 8 cases to the bladder and in the last 8 to the ileum. Patient survival at 10 years was 81%, pancreatic graft 82% and 65% renal graft. The most relevant postoperative complication was sepsis, killing two patients. The immune complications were presented in eight patients. It was acute rejection, being managed with steroid therapy or thymoglobuline

Precise tracking of vaccine-responding T-cell clones reveals convergent and personalized response in identical twins

T-cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical framework to detect TCR clone proliferation and contraction from longitudinal repertoire data. We applied this framework to data from three pairs of identical twins immunized with the yellow fever vaccine. We identified 500-1500 responding TCRs in each donor and validated them using three independent assays. While the responding TCRs were mostly private, albeit with higher overlap between twins, they could be well predicted using a classifier based on sequence similarity. Our method can also be applied to samples obtained post-infection, making it suitable for systematic discovery of new infection-specific TCRs in the clinic

The health status of children without resident permit consulting the Children's Hospital of Lausanne.

OBJECTIVE: To assess social, economic and medical data concerning children without a resident permit taken into care by the Children's Hospital of Lausanne (HEL) in order to evaluate their specific needs. METHODS: Prospective exploratory study by a questionnaire including the socio-demographic, medical and education data of 103 children without a resident permit, who consulted the HEL for the first time between August 2003 and March 2006. These children were then recalled for a second check-up one year later in order to allow a regular monitoring. RESULTS: Eighty-seven percent of the children were native of Latin America, 36% being less than two years old. This population of children lived in precarious conditions with a family income lower than the poverty level (89% of the families with less than 3100 CHF/month). Forty-five percent of the children had a health insurance. The main reasons for consultation were infectious diseases, a check-up requested by the school or a check-up concerning newborn children. Most of them were in good health and the others were affected by illnesses similar to those found in other children of the same age. At least 13% of the children were obese and 27% were overweight. All children who were of educational age went to school during the year after the first check-up and 48% were affiliated to a health insurance. CONCLUSIONS: The majority of the children from Latin America lived in very precarious conditions. Their general health status was good and most of them could benefit from regular check-ups. Prevention, focused on a healthier life style, was particularly important among this population characterised by a high incidence of overweight and obesity

Etre malade et « sans-papiers » à Lausanne : quo vadis ?

Parmi les populations migrantes, la proportion des patients sans permis de séjour valable en Suisse - les «sans-paplers» - est en constante augmentation. Il s'agit surtout de Jeunes femmes latino-américaines accompagnées d'un ou plusieurs de leurs enfants. Les soins préventifs et ou thérapeutiques que nécessite cette population vulnérable sont prodigués à Lausanne dans des institutions telles que la Policlinique médicale universitaire et l'Hôpital de l'Enfance. Une véritable volonté Institutionnelle, une prise en charge multidisciplinaire et un système d'accueil infirmier puis - si nécessaire -une prise en charge par un médecin de premier recours, dans un climat de confiance réciproque sont autant d'éléments permettant de leur prodiguer des soins de qualité. L'application du principe de l'affiliation obligatoire à une assurance, application souhaitée par la Confédération, devrait être généralisée

NoisET: Noise learning and Expansion detection of T-cell receptors

High-throughput sequencing of T- and B-cell receptors makes it possible to track immune repertoires across time, in different tissues, in acute and chronic diseases and in healthy individuals. However quantitative comparison between repertoires is confounded by variability in the read count of each receptor clonotype due to sampling, library preparation, and expression noise. We review methods for accounting for both biological and experimental noise and present an easy-to-use python package NoisET that implements and generalizes a previously developed Bayesian method. It can be used to learn experimental noise models for repertoire sequencing from replicates, and to detect responding clones following a stimulus. We test the package on different repertoire sequencing technologies and datasets. We review how such approaches have been used to identify responding clonotypes in vaccination and disease data. Availability: NoisET is freely available to use with source code at github.com/statbiophys/NoisET