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Link: Ranking Each Game on the 2016 Notre Dame Football Schedule
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How far any single loss would drop the Irish in the PC's final rankings?
I think the best loss would be to Duke, Syracuse, or NC State. They're at least Power 5, and we can't miss the opportunity to have every possible marquee win on the resume with only 12 total games.
In general, the earlier the loss the better. An L after Stanford is an almost certain Playoff killer.