Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Filocrono em batateira afetado pelo tamanho do tubérculo-semente e pela época de cultivo Phyllocrono in potato affected by tuber-seed size and growing season

O objetivo deste trabalho foi estimar o filocrono de plantas de batata da cultivar Asterix oriundas de diferentes tamanhos de tubérculos-semente, em duas épocas de cultivo em campo utilizando o conceito de graus-dia para o cálculo do filocrono. O experimento foi desenvolvido em Santa Maria (RS), na primavera de 2003 e no outono de 2004. Foram usados quatro tamanhos de tubérculos-semente da cultivar de batata Asterix: entre 2 e 4 cm, 4 e 6 cm, 6 e 8 cm e 8 e 10 cm. O filocrono (ºC dia folha-1) foi estimado pelo inverso do coeficiente angular da relação entre número de folhas na haste principal e a soma térmica calculada por três métodos: método 1 - considera apenas a temperatura base; método 2 - considera a temperatura base e a temperatura ótima, e método 3 - considera a temperatura base, a temperatura ótima e a temperatura máxima. O tamanho do tubérculo-semente não afetou o filocrono, mas o método de cálculo da soma térmica e a época de cultivo afetaram o filocrono da batateira cultivar Asterix. No método de cálculo da soma térmica a ser usado no filocrono da batateira cultivar Asterix, recomenda-se usar a temperatura base e a temperatura ótima, pois com este método, o filocrono foi similar entre as épocas de cultivo.<br>The objective of this study was to estimate the phyllochron of the potato cultivar Asterix in plants derived from different tuber seed sizes in two field growing seasons using the concept of degrees-days for calculating the phyllochron. The experiment was conducted in Santa Maria, RS, during Spring 2003 and Fall 2004. Four classes of tuber-seed diameter of the potato cultivar Asterix were used: 2-4 cm, 4-6 cm, 6-8 cm and 8-10 cm. The phyllochron was estimated as the inverse of the slope of the linear regression of main stem leaves number against the thermal time calculated with three methods: method 1 - considering only the base temperature, method 2 - considering the base temperature and the optimum temperature, and method 3 - considering the base temperature, the optimum temperature and the maximum temperature. Tuber-seed size did not affect the phyllochron of the potato cultivar Asterix, but the method of calculating thermal time and the planting date affected the phyllochron. For the method of calculating thermal time in the phyllochron of the potato cultivar Asterix, it is recommended to use the base temperature and the optimum temperature, because it produced similar phyllochron values in the two growing seasons