Nadin Rohland and David Reich present a cost-effective, high-throughput method for producing DNA sequencing libraries, which can be used for multiplexed target capture. The method reduces the cost of library preparation to about $15 per sample and allows for the simultaneous enrichment of approximately 100 individually barcoded samples for a subset of the genome. The authors demonstrate the effectiveness of this approach by generating libraries for over 2000 samples from a prostate cancer study, enriching them for a 2.2-Mb subset of the genome, and obtaining data that are effective for polymorphism discovery. The method is also suitable for whole-genome sequencing and microbial sequencing, showing high coverage and low duplication rates. The authors discuss the advantages and limitations of their method, including the use of short adapters to reduce interference during hybrid capture and the need for careful normalization to achieve uniform coverage across samples.Nadin Rohland and David Reich present a cost-effective, high-throughput method for producing DNA sequencing libraries, which can be used for multiplexed target capture. The method reduces the cost of library preparation to about $15 per sample and allows for the simultaneous enrichment of approximately 100 individually barcoded samples for a subset of the genome. The authors demonstrate the effectiveness of this approach by generating libraries for over 2000 samples from a prostate cancer study, enriching them for a 2.2-Mb subset of the genome, and obtaining data that are effective for polymorphism discovery. The method is also suitable for whole-genome sequencing and microbial sequencing, showing high coverage and low duplication rates. The authors discuss the advantages and limitations of their method, including the use of short adapters to reduce interference during hybrid capture and the need for careful normalization to achieve uniform coverage across samples.