PubMed HealthSearch

PubMed · 7604154

A hybrid likelihood algorithm for risk modelling.

Abstract

The risk of radiation-induced cancer is assessed through the follow-up of large cohorts, such as atomic bomb survivors or underground miners who have been occupationally exposed to radon and its decay products. The models relate to the dose, age and time dependence of the excess tumour rates, and they contain parameters that are estimated in terms of maximum likelihood computations. The computations are performed with the software package EPI-CURE, which contains the two main options of person-by person regression or of Poisson regression with grouped data. The Poisson regression is most frequently employed, but there are certain models that require an excessive number of cells when grouped data are used. One example involves computations that account explicitly for the temporal distribution of continuous exposures, as they occur with underground miners. In past work such models had to be approximated, but it is shown here that they can be treated explicitly in a suitably reformulated person-by person computation of the likelihood. The algorithm uses the familiar partitioning of the log-likelihood into two terms, L1 and L0. The first term, L1, represents the contribution of the 'events' (tumours). It needs to be evaluated in the usual way, but constitutes no computational problem. The second term, L0, represents the event-free periods of observation. It is, in its usual form, unmanageable for large cohorts. However, it can be reduced to a simple form, in which the number of computational steps is independent of cohort size. The method requires less computing time and computer memory, but more importantly it leads to more stable numerical results by obviating the need for grouping the data. The algorithm may be most relevant to radiation risk modelling, but it can facilitate the modelling of failure-time data in general.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A M Kellerer, M Kreisheimer, D Chmelevsky, D Barclay. 1995. A hybrid likelihood algorithm for risk modelling.. https://doi.org/10.1007/bf01210540

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

A note on a generalized single step theory for any number of hierarchical genomic matrices.

BACKGROUND: The Single Step algorithm allows combining information from genotyped and un-genotyped individuals, provided they are connected by a pedigree. However, current single step theory is limited to a single list of markers. RESULTS: We present a generalized single step (GSS) method that can accommodate any number of hierarchical molecular datasets (e.g. sequence, high and low density arrays) and pedigree, avoiding imputation. We prove that a similar efficient inversion algorithm exists. The method is recursive, starting with the highest marker density scenario. We illustrate the method with simulation and show that GSS can increase predictive accuracy compared to standard single step. R code is provided so that custom scenarios can be easily compared, either with simulated or real data. CONCLUSION: The method developed generalizes extant single step theory to any number of hierarchical molecular relationship matrices, broadening the scenarios where single step can be applied. A topic of particular interest can be ecology field data or human populations where pedigree is not available, but where samples sequenced and genotyped at different densities can exist. GSS can also be a useful tool to optimize allocation of genotyping and / or sequencing resources.

Algorithms

cgDist: Nucleotide-level distance calculation from cgMLST allelic profiles.

Bacterial genomic surveillance requires balancing computational efficiency with genetic resolution for effective cluster investigation. cgMLST distance calculations treat all allelic differences as equivalent units, obscuring nucleotide-level variation. Furthermore, single nucleotide polymorphism-based pipelines provide finer resolution at substantially higher computational cost, which limits their routine deployment in surveillance laboratories. We present cgDist, an algorithm that calculates nucleotide-level distances directly from cgMLST allelic profiles, providing finer resolution than allele-count distances by leveraging within-allele nucleotide variation. The cache architecture stores alignment statistics, enabling distance calculation modes without computation and supporting both dataset-specific and schema-complete cache generation. This design enables incremental surveillance analysis, with performance benefits as laboratories accumulate alignment data. cgDist functions as a precision 'zoom lens' for the investigation of clusters identified through initial cgMLST screening. Rather than restructuring population relationships, this targeted approach concentrates enhanced resolution where it is most informative. The algorithm ensures that cgDist distances are greater than or equal to corresponding cgMLST distances, preserving epidemiological interpretability while adding genetic discrimination. By increasing resolution within identified clusters, cgDist may also support outbreak investigation, a potential application that remains to be evaluated on outbreak-derived data.

Algorithms

Theseus: fast and optimal affine-gap sequence-to-graph alignment.

MOTIVATION: Sequence-to-graph alignment is a central problem in bioinformatics, with applications in multiple sequence alignment (MSA) and pangenome analysis, among others. However, current algorithms for optimal affine-gap alignment impose high memory and computational requirements, limiting their scalability to aligning long sequences to complex graphs. Practical solutions partially address this problem using heuristic strategies that ultimately trade off optimality for speed. RESULTS: This work presents Theseus, a novel, fast, and optimal affine-gap sequence-to-graph alignment algorithm. Theseus leverages similarities between genomic sequences to accelerate the alignment computation and reduces the overall memory requirements without compromising optimality. To that end, Theseus processes only a subset of the dynamic programming cells, using a sparse-data strategy that enables efficient sequence-to-graph alignment. Moreover, our algorithm supports optimal affine-gap alignment on arbitrary directed graphs, including those with cycles. We evaluate Theseus on two key problems: MSA and pangenome read mapping. For MSA, we compare it against SPOA, abPOA, and POASTA. Theseus is 1.6× to 17.6× faster than POASTA, and 7.3× faster, on average, than SPOA, both optimal aligners. Compared with abPOA, Theseus ensures optimality and scales to the largest problems. For pangenome read mapping, we benchmark Theseus against the alignment stage of the mapping tool vg map, along with the alignment kernels of SPOA, abPOA, and POASTA. Theseus outperforms the other methods, showing a 1.9× to 16.9× speedup on short reads. Moreover, Theseus is 1.5× to 36.3× faster than vg when aligning against synthetic cyclic graphs. AVAILABILITY AND IMPLEMENTATION: Theseus code and documentation are publicly available at https://github.com/albertjimenezbl/theseus-lib.

Algorithms