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Contaminación de bajo nivel confunde el análisis genómico poblacional

Audrey K Ward1, Eduardo F C Scopel2, Brent Shuman3

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G3 (Bethesda, Md.)
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La contaminación genómica intraespecífica se puede detectar mediante gráficos de frecuencia de alelos B. Incluso niveles bajos de contaminación pueden alterar significativamente los análisis filogenéticos y conducir a una identificación errónea de híbridos genéticos.

Palabras clave:
gráficos BAFcontaminación cruzadaheterocigosidadfilogenómicagenómica de poblacionesestructura poblacionalllamadas de polimorfismos de un solo nucleótido (SNP)

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Área de la Ciencia:

  • Genómica
  • Bioinformática
  • Genética de Poblaciones

Sus antecedentes:

  • La contaminación del genoma secuenciado representa un desafío en la investigación biológica.
  • Estudios previos abordaron principalmente la contaminación interespecífica o genomas procariotas.
  • La contaminación intraespecífica, especialmente en eucariotas, sigue estando menos explorada.

Objetivo del estudio:

  • Investigar la prevalencia e impacto de la contaminación genómica intraespecífica.
  • Desarrollar y validar un método para detectar dicha contaminación.
  • Evaluar los efectos de la contaminación en los análisis genómicos posteriores.

Principales métodos:

  • Se analizaron 1,298 secuencias de genomas de Saccharomyces cerevisiae en busca de contaminación.
  • Se mapearon datos de genomas de lecturas cortas a genomas de referencia.
  • Se visualizaron diferencias de nucleótidos únicos para identificar frecuencias de alelos secundarios.
  • Se utilizaron datos contaminados in silico para validar los métodos de detección.
  • Se evaluaron los efectos de la contaminación en los análisis de mezcla y filogenéticos en dos especies de hongos.

Principales resultados:

  • Se identificó al menos un 5% de contaminación en 8 de 1,298 genomas de Saccharomyces cerevisiae.
  • Las tasas de contaminación variaron significativamente entre los centros de secuenciación y los estudios.
  • Los gráficos de frecuencia de alelos secundarios identificaron eficazmente la contaminación con tan solo un 5% de frecuencia de alelos B.
  • Los niveles de contaminación del 5-10% distorsionaron las topologías de los árboles filogenéticos y sugirieron una falsa mezcla.

Conclusiones:

  • La contaminación genómica intraespecífica es detectable utilizando gráficos de frecuencia de alelos B.
  • Las canalizaciones estándar de llamada de bases pueden no revelar contaminación superficial.
  • Incluso niveles bajos de contaminación pueden impactar críticamente los análisis filogenéticos y de mezcla.
  • Se recomiendan los gráficos de frecuencia de alelos B como una herramienta de cribado estándar para datos de resecuenciación del genoma.