Paper List
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An AI Implementation Science Study to Improve Trustworthy Data in a Large Healthcare System
This paper addresses the critical gap between theoretical AI research and real-world clinical implementation by providing a practical framework for as...
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The BEAT-CF Causal Model: A model for guiding the design of trials and observational analyses of cystic fibrosis exacerbations
This paper addresses the critical gap in cystic fibrosis exacerbation management by providing a formal causal framework that integrates expert knowled...
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Hierarchical Molecular Language Models (HMLMs)
This paper addresses the core challenge of accurately modeling context-dependent signaling, pathway cross-talk, and temporal dynamics across multiple ...
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Stability analysis of action potential generation using Markov models of voltage‑gated sodium channel isoforms
This work addresses the challenge of systematically characterizing how the high-dimensional parameter space of Markov models for different sodium chan...
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Approximate Bayesian Inference on Mechanisms of Network Growth and Evolution
This paper addresses the core challenge of inferring the relative contributions of multiple, simultaneous generative mechanisms in network formation w...
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EnzyCLIP: A Cross-Attention Dual Encoder Framework with Contrastive Learning for Predicting Enzyme Kinetic Constants
This paper addresses the core challenge of jointly predicting enzyme kinetic parameters (Kcat and Km) by modeling dynamic enzyme-substrate interaction...
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Tissue stress measurements with Bayesian Inversion Stress Microscopy
This paper addresses the core challenge of measuring absolute, tissue-scale mechanical stress without making assumptions about tissue rheology, which ...
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DeepFRI Demystified: Interpretability vs. Accuracy in AI Protein Function Prediction
This study addresses the critical gap between high predictive accuracy and biological interpretability in DeepFRI, revealing that the model often prio...
pHapCompass: Probabilistic Assembly and Uncertainty Quantification of Polyploid Haplotype Phase
School of Computing, University of Connecticut | Department of Entomology and Plant Pathology, University of Tennessee | Institute for Systems Genomics, University of Connecticut
30秒速读
IN SHORT: This paper addresses the core challenge of accurately assembling polyploid haplotypes from sequencing data, where read assignment ambiguity and an exponential search space of possible phasings have hindered reliable reconstruction and uncertainty quantification.
核心创新
- Methodology Introduces pHapCompass, the first probabilistic haplotype assembler for diploid and polyploid genomes that explicitly models read assignment ambiguity to compute a distribution over haplotype phasings, enabling formal uncertainty quantification.
- Methodology Develops two distinct graph-theoretic algorithms: pHapCompass-short (a Markov random field for high-coverage short reads) and pHapCompass-long (a hierarchical mixture model for low-coverage long reads), both designed to scale with genomic complexity.
- Methodology Creates the first computational workflow for simulating realistic auto- and allopolyploid genomes and sequencing data, addressing a critical gap in benchmarking tools that previously relied on oversimplified synthetic genomes.
主要结论
- pHapCompass demonstrates competitive performance against existing assemblers across varying ploidy levels, coverage depths, and mutation rates, while uniquely providing accurate quantification of phase uncertainty.
- The developed simulation workflow generates more realistic benchmarking datasets, revealing that prior methods often overestimate performance on simplistic synthetic genomes.
- The framework successfully assembled an allo-octoploid strawberry chromosome, showcasing practical applicability to complex, real-world polyploid genomes.
摘要: Computing haplotypes from sequencing data, i.e. haplotype assembly, is an important component of foundational molecular and population genetics problems, including interpreting the effects of genetic variation on complex traits and reconstructing genealogical relationships. Assembling the haplotypes of polyploid genomes remains a significant challenge due to the exponential search space of haplotype phasings and read assignment ambiguity; the latter challenge is particularly difficult for polyploid haplotype assemblers since the information contained within the observed sequence reads is often insufficient for unambiguous haplotype assignment in polyploid genomes. We present pHapCompass, probabilistic haplotype assembly algorithms for diploid and polyploid genomes that explicitly model and propagate read assignment ambiguity to compute a distribution over polyploid haplotype phasings. We develop graph theoretic algorithms to enable statistical inference and uncertainty quantification despite an exponential space of possible phasings. Since prior work evaluates polyploid haplotype assembly on synthetic genomes that do not reflect the realistic genomic complexity of polyploidy organisms, we develop a computational workflow for simulating genomes and DNA-seq for auto- and allopolyploids. Additionally, we generalize the vector error rate and minimum error correction evaluation criteria for partially phased haplotypes. Benchmarking of pHapCompass and several existing polyploid haplotype assemblers shows that pHapCompass yields competitive performance across varying genomic complexities and polyploid structures while retaining an accurate quantification of phase uncertainty. The source code for pHapCompass, simulation scripts, and datasets are freely available at https://github.com/bayesomicslab/pHapCompass.