Biology subjects

Lladser, M. E.

Publications and source records attributed to Lladser, M. E..

6 recordsLinked to original sources

bioRxiv2026

Enabling Megascale Microbiome Analysis with DartUniFrac

We introduce a new algorithm, DartUniFrac, and a near-optimal implementation with GPU acceleration, up to three orders of magnitude faster than the state of the art and scaling to millions of samples (pairwise) and billions of taxa. DartUniFrac connects UniFrac with weighted Jaccard similarity and exploits sketching algorithms for fast computation. We benchmark DartUniFrac against exact UniFrac implementations, demonstrating that DartUniFrac is statistically indistinguishable from them on real-world microbiome and metagenomic datasets.

bioinformatics↗

bioRxiv2026

The Phylogenetic Structure of β-diversity: Covariance Matrix Sparsification of Critical Beta-splitting Trees

Haar-like wavelets sparsify the phylogenetic covariance matrices of large, uniformly random k-regular trees with overwhelmingly high probability. This motivates the Haar-like distance, a {beta}-diversity metric that implicitly ranks the splits of a reference phylogeny by their relevance in differentiating two microbial environments, offering an interpretation as to why the environments differ compositionally. Nevertheless, uniform binary trees exhibit statistical features distinct from those of the trees used by practitioners, leaving the extent of sparsification and the practical validity of the implied Haar-like distance speculative. To address this, our manuscript examines the sparsification of phylogenetic covariance matrices of large critical beta-splitting random trees, a model introduced to better reflect real-world phylogenies. By obtaining sharp asymptotic estimates of the first and second moments of the external path length in this ensemble, we demonstrate that the Haar-like basis also pseudo-diagonalizes the phylogenetic covariance matrix of most large trees in this more realistic framework. Additionally, we devise a test to assess the statistical significance of splits in the reference phylogeny identified by the Haar-like distance. We apply the test to a well-studied microbial mat to further substantiate the presumption that the identified splits represent genuine biological signals differentiating the top and bottom layers of the mat.

bioinformatics↗

bioRxiv2025

A periodic table of bacteria?: Mapping bacterial diversity in trait space

Bacterial diversity can be overwhelming. There is an ever-expanding number of bacterial taxa being discovered, but many of these taxa remain uncharacterized with unknown traits and environmental preferences. This diversity makes it challenging to interpret ecological patterns in microbiomes and understand why individual taxa, or assemblages, may vary across space and time. While we can use information from the rapidly growing databases of bacterial genomes to infer traits, we still need an approach to organize what we know, or think we know, about bacterial taxa to match taxonomic and phylogenetic information to trait inferences. Inspired by the periodic table of the elements, we have constructed a periodic table of bacterial taxa to organize and visualize monophyletic groups of bacteria based on the distributions of key traits predicted from genomic data. By analyzing 50,745 genomes across 31 bacterial phyla, we used the Haar-like wavelet transformation, a model-free transformation of trait data, to identify clades of bacteria which are nearly uniform with respect to six selected traits - oxygen tolerance, autotrophy, chlorophototrophy, maximum potential growth rate, GC content and genome size. The identified functionally uniform clades of bacteria are presented in a concise periodic table-like format to facilitate identification and exploration of bacterial lineages in trait space. While our approach could be improved and expanded in the future, we demonstrate its utility for integrating phylogenetic information with genome-derived trait values to improve our understanding of the bacterial diversity found in environmental and host-associated microbiomes.

bioinformatics↗

bioRxiv2023

Interpretable Metric Learning in Comparative Metagenomics: The Adaptive Haar-like Distance

Random forests have emerged as a promising tool in comparative metagenomics because they can predict environmental characteristics based on microbial composition in datasets where {beta}-diversity metrics fall short of revealing meaningful relationships between samples. Nevertheless, despite this efficacy, they lack biological insight in tandem with their predictions, potentially hindering scientific advancement. To overcome this limitation, we leverage a geometric characterization of random forests to introduce a data-driven phylogenetic {beta}-diversity metric, the adaptive Haar-like distance. This new metric assigns a weight to each internal node (i.e., split or bifurcation) of a reference phylogeny, indicating the relative importance of that node in discerning environmental samples based on their microbial composition. Alongside this, a weighted nearest-neighbors classifier, constructed using the adaptive metric, can be used as a proxy for the random forest while maintaining accuracy on par with that of the original forest and another state-of-the-art classifier, CoDaCoRe. As shown in datasets from diverse microbial environments, however, the new metric and classifier significantly enhance the biological interpretability and visualization of high-dimensional metagenomic samples. Author summaryTraditional phylogenetic {beta}-diversity metrics, particularly weighted and unweighted UniFrac, have had great success in comparing and visualizing high-dimensional metagenomic samples. Nonetheless, these metrics rely upon pre-established biological assumptions that might not capture key microbial players or relationships between some samples. On the contrary, supervised machine learning algorithms, such as random forests, can often capture intricate relationships between microbial samples; however, unveiling these relationships is often challenging due to the intricate inner mechanisms inherent to these algorithms. The adaptive Haar-like distance integrates the merits of {beta}-diversity metrics and random forests, allowing for precise, intuitive, and visual comparison of metagenomic samples, offering valuable scientific insight into the distinctions and associations among microbial environments.

microbiology↗

bioRxiv2022

Sparsification of Large Ultrametric Matrices: Insights into the Microbial Tree of Life

Strictly ultrametric matrices appear in many domains of mathematics and science; nevertheless, they can be large and dense, making them difficult to store and manipulate, unlike large but sparse matrices. In this manuscript, we exploit that strictly ultrametric matrices can be represented as binary trees to sparsify them via an orthonormal base change based on Haar-like wavelets. We show that, with overwhelmingly high probability, only an asymptotically negligible fraction of the off-diagonal entries in random but large strictly ultrametric matrices remain non-zero after the base change; and develop an algorithm to sparsify such matrices directly from their tree representation. We also identify the subclass of matrices diagonalized by the Haar-like wavelets and supply a sufficient condition to approximate the spectrum of strictly ultrametric matrices outside this subclass. Our methods give computational access to the covariance matrix of the microbiologists Tree of Life, which was previously inaccessible due to its size, and motivate introducing a new wavelet-based (beta-diversity) metric to compare microbial environments. Unlike the established (beta-diversity) metrics, the new metric may be used to identify internal nodes (i.e., splits) in the Tree that link microbial composition and environmental factors in a statistically significant manner. MSC codes05C05, 15A18, 42C40, 65F55, 92C70

microbiology↗

bioRxiv2020

On Contamination of Symbolic Datasets

Data taking values on discrete sample spaces are the embodiment of modern biological research. "Omics" experiments produce millions of symbolic outcomes in the form of reads (i.e., DNA sequences of a few dozens to a few hundred nucleotides). Unfortunately, these intrinsically non-numerical datasets are often highly contaminated, and the possible sources of contamination are usually poorly characterized. This contrasts with numerical datasets where Gaussian-type noise is often well-justified. To overcome this hurdle, we introduce the notion of latent weight, which measures the largest expected fraction of samples from a contaminated probabilistic source that conform to a model in a well-structured class of desired models. We examine various properties of latent weights, which we specialize to the class of exchangeable probability distributions. As proof of concept, we analyze DNA methylation data from the 22 human autosome pairs. Contrary to what it is usually assumed, we provide strong evidence that highly specific methylation patterns are overrepresented at some genomic locations when contamination is taken into account.

genomics↗