ManiNetCluster: a novel manifold learning approach to reveal the functional links between gene networks.

BACKGROUND:The coordination of genomic functions is a critical and complex process across biological systems such as phenotypes or states (e.g., time, disease, organism, environmental perturbation). Understanding how the complexity of genomic function relates to these states remains a challenge. To address this, we have developed a novel computational method, ManiNetCluster, which simultaneously aligns and clusters gene networks (e.g., co-expression) to systematically reveal the links of genomic function between different conditions. Specifically, ManiNetCluster employs manifold learning to uncover and match local and non-linear structures among networks, and identifies cross-network functional links. RESULTS:We demonstrated that ManiNetCluster better aligns the orthologous genes from their developmental expression profiles across model organisms than state-of-the-art methods (p-value <2.2×10-16). This indicates the potential non-linear interactions of evolutionarily conserved genes across species in development. Furthermore, we applied ManiNetCluster to time series transcriptome data measured in the green alga Chlamydomonas reinhardtii to discover the genomic functions linking various metabolic processes between the light and dark periods of a diurnally cycling culture. We identified a number of genes putatively regulating processes across each lighting regime. CONCLUSIONS:ManiNetCluster provides a novel computational tool to uncover the genes linking various functions from different networks, providing new insight on how gene functions coordinate across different conditions. ManiNetCluster is publicly available as an R package at https://github.com/daifengwanglab/ManiNetCluster

Speech vocoding for laboratory phonology

Using phonological speech vocoding, we propose a platform for exploring relations between phonology and speech processing, and in broader terms, for exploring relations between the abstract and physical structures of a speech signal. Our goal is to make a step towards bridging phonology and speech processing and to contribute to the program of Laboratory Phonology. We show three application examples for laboratory phonology: compositional phonological speech modelling, a comparison of phonological systems and an experimental phonological parametric text-to-speech (TTS) system. The featural representations of the following three phonological systems are considered in this work: (i) Government Phonology (GP), (ii) the Sound Pattern of English (SPE), and (iii) the extended SPE (eSPE). Comparing GP- and eSPE-based vocoded speech, we conclude that the latter achieves slightly better results than the former. However, GP - the most compact phonological speech representation - performs comparably to the systems with a higher number of phonological features. The parametric TTS based on phonological speech representation, and trained from an unlabelled audiobook in an unsupervised manner, achieves intelligibility of 85% of the state-of-the-art parametric speech synthesis. We envision that the presented approach paves the way for researchers in both fields to form meaningful hypotheses that are explicitly testable using the concepts developed and exemplified in this paper. On the one hand, laboratory phonologists might test the applied concepts of their theoretical models, and on the other hand, the speech processing community may utilize the concepts developed for the theoretical phonological models for improvements of the current state-of-the-art applications

Principles for the post-GWAS functional characterisation of risk loci

Several challenges lie ahead in assigning functionality to susceptibility SNPs. For example, most effect sizes are small relative to effects seen in monogenic diseases, with per allele odds ratios usually ranging from 1.15 to 1.3. It is unclear whether current molecular biology methods have enough resolution to differentiate such small effects. Our objective here is therefore to provide a set of recommendations to optimize the allocation of effort and resources in order maximize the chances of elucidating the functional contribution of specific loci to the disease phenotype. It has been estimated that 88% of currently identified disease-associated SNP are intronic or intergenic. Thus, in this paper we will focus our attention on the analysis of non-coding variants and outline a hierarchical approach for post-GWAS functional studies