genefirst

Genefirst is a term used in genetics and bioinformatics to describe a gene-centric approach to research and clinical interpretation. It denotes strategies that begin with genes or gene-level data and then link findings to phenotypes, rather than starting from phenotypes or diseases. The concept is often described as a gene-first or gene-centric framework and contrasts with phenotype-first approaches and with traditional forward genetics.

The approach gained emphasis as high-throughput sequencing and functional annotation resources improved the ability to evaluate the relevance of individual genes. In genefirst workflows, researchers may combine exome or genome sequencing with gene prioritization algorithms, functional annotations, and network analyses to nominate candidate genes for further study. Cross-species and model-organism data are commonly incorporated to strengthen gene-disease associations.

Applications include rare disease gene discovery, where clinicians use gene-first pipelines to identify causal or contributory genes in unsolved cases, and pharmacogenomics or target discovery, where gene-centric analyses help identify drug targets or pathways affected by genetic variation. In clinical settings, genefirst approaches can support diagnostic decision-making and personalized treatment planning when integrated with phenotypic information.

Limitations of genefirst strategies include potential biases toward well-annotated genes, difficulties in interpreting variants of uncertain significance, and the risk of missing non-genic regulatory elements or polygenic contributions. Effective use often requires integrating phenotypic data, rigorous statistical controls, and validation in independent datasets or functional assays.

Genefirst remains one of several complementary strategies in modern genomics, alongside phenotype-first, forward genetics, and systems biology approaches, supported by expanding databases and cross-disciplinary collaboration.