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To cross the Appalachians easily, take the C&O Trail/GAP out of DC to Pittsburgh. Lots of single females on that run. Again your option.The GAP is pretty easy riding but the C&O can be miserable riding, particularly if it's wet. Neither are particularly good on a narrow tire road bike so plan on 700-28 or larger tires if you go that route.
I'd recommend West to East because of the prevailing winds. I remember meeting people coming from your direction. When I asked them how they were doing, they said that besides riding against the wind for 3,000 miles, they were doing just peachy. But that's your option.