NOMAD is a state-of-the-art software package for optimizing blackbox problems. In continuous development since 2001, it constantly evolved with the integration of new algorithmic features published in scientific publications. These features are motivated by real applications encountered by industrial partners. The latest major release of NOMAD , version 3, dates to 2008. Minor releases are produced as new features are incorporated. The present work describes NOMAD 4, a complete redesign of the previous version, with a new architecture providing more flexible code, added functionalities, and reusable code. We introduce algorithmic components, which are building blocks for more complex algorithms and can initiate other components, launch nested algorithms, or perform specialized tasks. They facilitate the implementation of new ideas, including the MegaSearchPoll component, warm and hot restarts, and a revised version of the PsdMads algorithm. Another main improvement of NOMAD 4 is the usage of parallelism, to simultaneously compute multiple blackbox evaluations and to maximize usage of available cores. Running different algorithms, tuning their parameters, and comparing their performance for optimization are simpler than before, while overall optimization performance is maintained between versions 3 and 4. NOMAD is freely available at www.gerad.ca/nomad and the whole project is visible at github.com/bbopt/nomad.

BACKGROUND: PSEUDOMARKER is a software package that performs joint linkage and linkage disequilibrium analysis between a marker and a putative disease locus. A key feature of PSEUDOMARKER is that it can combine case-controls and pedigrees of varying structure into a single unified analysis. Thus it maximizes the full likelihood of the data over marker allele frequencies or conditional allele frequencies on disease and recombination fraction. RESULTS: The new version 2.0 uses the software package NOMAD to maximize likelihoods, resulting in generally comparable or better optima with many fewer evaluations of the likelihood functions. CONCLUSIONS: After being modified substantially to use modern optimization methods, PSEUDOMARKER version 2.0 is more robust and substantially faster than version 1.0. NOMAD may be useful in other bioinformatics problems where complex likelihood functions are optimized.